Preventing ICU Subsyndromal Delirium Conversion to Delirium with Low Dose IV Haloperidol: A Double-Blind, Placebo-Controlled Pilot Study

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Al-Qadheeb, Nada S.; Skrobik, Yoanna; Schumaker, Greg; Pacheco, Manuel; Roberts, Russel; Ruthazer, Robin; Devlin, John W

2016-01-01

Objective To compare the efficacy and safety of scheduled low-dose, haloperidol vs. placebo for the prevention of delirium [Intensive Care Delirium Screening Checklist (ICDSC) ≥ 4)] administered to critically ill adults with subsyndromal delirium (ICDSC = 1-3). Design Randomized, double-blind, placebo-controlled trial. Setting Three 10-bed ICUs (2 medical; 1 surgical) at an academic medical center in the U.S. Patients Sixty-eight mechanically ventilated patients with subsyndromal delirium without complicating neurologic conditions, cardiac surgery or requiring deep sedation. Interventions Patients were randomly assigned to receive intravenous haloperidol 1 mg or placebo every six hours until either delirium (ICDSC ≥ 4 with psychiatric confirmation), therapy ≥ 10 days or ICU discharge occurred. Measurements and Main Results Baseline characteristics were similar between the haloperidol (n=34) and placebo (n=34) groups. A similar number of patients given haloperidol [12/34 (35%)] and placebo [8/34 (23%)] patients developed delirium (p=0.29). Haloperidol use reduced the hours per study day spent agitated (SAS ≥ 5) (p=0.008), but did not influence the proportion of 12-hour ICU shifts patients’ spent alive without coma (SAS ≤ 2) or delirium (p=0.36), the time to first delirium occurrence (p=0.22) nor delirium duration (p=0.26). Days of mechanical ventilation (p=0.80), ICU mortality (p=0.55) and ICU patient disposition (p=0.22) were similar in the two groups. The proportion of patients who developed QTc-interval prolongation (p=0.16), extrapyramidal symptoms (p=0.31), excessive sedation (p=0.31) or new-onset hypotension (p=1.0) that resulted in study drug discontinuation was comparable between the two groups. Conclusions Low-dose scheduled haloperidol, initiated early in the ICU stay, does not prevent delirium and has little therapeutic advantage in mechanically ventilated, critically ill adults with subsyndromal delirium. PMID:26540397

False sense of safety by daily QTc interval monitoring during methadone IVPCA titration in a patient with chronic pain

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Miranda-Grajales H

2013-05-01

Full Text Available Hector Miranda-Grajales, Joy Hao, Ricardo A CrucianiDepartment of Pain Medicine and Palliative Care, Beth Israel Medical Center, New York, NY, USAAbstract: It has been proposed that some deaths attributed to methadone are related to prolongation of the QTc interval; however, there are no clear recommendations on electrocardiogram (ECG monitoring in patients undergoing intravenous methadone infusion. This is a report on a patient receiving methadone intravenous patient-controlled analgesia titration for the treatment of chronic pain. Initially, her daily ECGs showed QTc intervals within normal limits; however, she experienced a rapid increase in QTc interval from 317 ms to 784 ms within a 24-hour period after methadone had been discontinued for excessive sedation. QTc interval greater than 500 ms is considered to be high risk for the fatal arrhythmia Torsades de Pointes. Daily ECGs did not detect a gradual increase in the QTc interval that would have alerted the medical staff of the need to decrease or stop the methadone before reaching a prolonged QTc interval associated with cardiotoxicity. In selected cases where aggressive methadone titration is required, more intensive monitoring, such as telemetry or ECG determinations every 12 hours, might help detect changes in QTc interval duration that might otherwise be missed by daily ECG determinations.Keywords: methadone, QTc prolongation, opioids, opioid side effects, IVPCA methadone

QTc interval prolongation in HIV-infected patients: a case–control study by 24-hour Holter ECG recording

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Fiorentini Alessandra

2012-12-01

Full Text Available Abstract Background Aim of the study was to assess QTc interval by a 24-hour ECG recording in a group of HIV-infected individuals with a basal prolonged QTc. The risk factors associated with QTc prolongation and the indices of cardiovascular autonomic control were also evaluated. Methods A case–control study was performed using as cases 32 HIV-infected patients with prolonged (>440 msec QTc interval as assessed by Holter ECG, and as controls 64 HIV-infected subjects with normal QTc interval. Autonomic function was evaluated by heart rate variability analysis during 24-hour recording. Results Duration of HIV disease was significantly longer among cases than among controls (p=0.04. Waist/hip ratio was also higher among cases than among controls (p=0.05. Frequency domain analysis showed the absence of physiologic decrease of low frequency (LF in the night period in both cases and controls. The LF night in cases showed a statistically significant reduction when compared with controls (p=0.007. Conclusions In our study group, QTc interval prolongation was associated with a longer duration of HIV infection and with a greater waist/hip ratio. HIV patients with QTc interval prolongation and with a longer duration of HIV infection were more likely to have an impairment of parasympathetic and sympathetic cardiac component.

A Randomized Controlled Trial of Intravenous Haloperidol vs. Intravenous Metoclopramide for Acute Migraine Therapy in the Emergency Department.

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Gaffigan, Matthew E; Bruner, David I; Wason, Courtney; Pritchard, Amy; Frumkin, Kenneth

2015-09-01

Emergency Department (ED) headache patients are commonly treated with neuroleptic antiemetics like metoclopramide. Haloperidol has been shown to be effective for migraine treatment. Our study compared the use of metoclopramide vs. haloperidol to treat ED migraine patients. A prospective, double-blinded, randomized control trial of 64 adults aged 18-50 years with migraine headache and no recognized risks for QT-prolongation. Haloperidol 5 mg or metoclopramide 10 mg was given intravenously after 25 mg diphenhydramine. Pain, nausea, restlessness (akathisia), and sedation were assessed with 100-mm visual analog scales (VAS) at baseline and every 20 min, to a maximum of 80 min. The need for rescue medications, side effects, and subject satisfaction were recorded. QTc intervals were measured prior to and after treatment. Follow-up calls after 48 h assessed satisfaction and recurrent or persistent symptoms. Thirty-one subjects received haloperidol, 33 metoclopramide. The groups were similar on all VAS measurements, side effects, and in their satisfaction with therapy. Pain relief averaged 53 mm VAS over both groups, with equal times to maximum improvement. Subjects receiving haloperidol required rescue medication significantly less often (3% vs. 24%, p haloperidol-treated subjects experiencing more restlessness (43% vs. 10%). Intravenous haloperidol is as safe and effective as metoclopramide for the ED treatment of migraine headaches, with less frequent need for rescue medications. Published by Elsevier Inc.

Effects of conventional vs high-dose rocuronium on the QTc interval during anesthesia induction and intubation in patients undergoing coronary artery surgery: a randomized, double-blind, parallel trial

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Öztürk, T.; Ağdanlı, D.; Bayturan, Ö.; Çıkrıkcı, C.; Keleş, G.T.

2015-01-01

Myocardial ischemia, as well as the induction agents used in anesthesia, may cause corrected QT interval (QTc) prolongation. The objective of this randomized, double-blind trial was to determine the effects of high- vs conventional-dose bolus rocuronium on QTc duration and the incidence of dysrhythmias following anesthesia induction and intubation. Fifty patients about to undergo coronary artery surgery were randomly allocated to receive conventional-dose (0.6 mg/kg, group C, n=25) or high-dose (1.2 mg/kg, group H, n=25) rocuronium after induction with etomidate and fentanyl. QTc, heart rate, and mean arterial pressure were recorded before induction (T0), after induction (T1), after rocuronium (just before laryngoscopy; T2), 2 min after intubation (T3), and 5 min after intubation (T4). The occurrence of dysrhythmias was recorded. In both groups, QTc was significantly longer at T3 than at baseline [475 vs 429 ms in group C (P=0.001), and 459 vs 434 ms in group H (P=0.005)]. The incidence of dysrhythmias in group C (28%) and in group H (24%) was similar. The QTc after high-dose rocuronium was not significantly longer than after conventional-dose rocuronium in patients about to undergo coronary artery surgery who were induced with etomidate and fentanyl. In both groups, compared with baseline, QTc was most prolonged at 2 min after intubation, suggesting that QTc prolongation may be due to the nociceptive stimulus of intubation. PMID:25714880

Effects of conventional vs high-dose rocuronium on the QTc interval during anesthesia induction and intubation in patients undergoing coronary artery surgery: a randomized, double-blind, parallel trial

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T. Öztürk

2015-04-01

Full Text Available Myocardial ischemia, as well as the induction agents used in anesthesia, may cause corrected QT interval (QTc prolongation. The objective of this randomized, double-blind trial was to determine the effects of high- vs conventional-dose bolus rocuronium on QTc duration and the incidence of dysrhythmias following anesthesia induction and intubation. Fifty patients about to undergo coronary artery surgery were randomly allocated to receive conventional-dose (0.6 mg/kg, group C, n=25 or high-dose (1.2 mg/kg, group H, n=25 rocuronium after induction with etomidate and fentanyl. QTc, heart rate, and mean arterial pressure were recorded before induction (T0, after induction (T1, after rocuronium (just before laryngoscopy; T2, 2 min after intubation (T3, and 5 min after intubation (T4. The occurrence of dysrhythmias was recorded. In both groups, QTc was significantly longer at T3 than at baseline [475 vs 429 ms in group C (P=0.001, and 459 vs 434 ms in group H (P=0.005]. The incidence of dysrhythmias in group C (28% and in group H (24% was similar. The QTc after high-dose rocuronium was not significantly longer than after conventional-dose rocuronium in patients about to undergo coronary artery surgery who were induced with etomidate and fentanyl. In both groups, compared with baseline, QTc was most prolonged at 2 min after intubation, suggesting that QTc prolongation may be due to the nociceptive stimulus of intubation.

QTc Prolongation in Veterans With Heroin Dependence on Methadone Maintenance Treatment.

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Hassamal, Sameer; Fernandez, Antony; Moradi Rekabdarkolaee, Hossein; Pandurangi, Ananda

2015-06-01

QTc prolongation and Torsade de Ppointes have been reported in patients on methadone maintenance. In this study, QTc was compared before and after the veteran (n = 49) was on a stable dosage of methadone for 8.72 ± 4.50 years to treat heroin dependence. Risk factors were correlated with the QTc once the veteran was on a stable dose of methadone. Differences in the clinical risk factors in subgroups of veterans with below and above mean QTc change was compared. ECG data was obtained from a 12-lead electrocardiogram (pre-methadone and on methadone) on 49 veterans. Data and risk factors were retrospectively collected from the medical records. The mean QTc at baseline (pre-methadone) was 426 ± 34 msec and after being on methadone for an average of 8.72 ± 4.50 years was significantly higher at 450 ± 35 msec. No significant relationships were found between QTc prolongation and risk factors except for calcium. The methadone dosage was significantly higher in veterans with a QTc change above the mean change of ≥ 24 msec (88.48 ± 27.20 mg v.s 68.96 ± 19.84 mg). None of the veterans experienced cardiac arrhythmias. The low complexity of medical co-morbidities may explain the lack of a significant correlation between any risk factor with the QTc except calcium and methadone dosage. The absence of TdP may be explained by the low prevalence of QTc values > 500 msec as well as the retrospective design of the study. During long-term methadone treatment, there was a slight increase in the QTc interval but we did not find evidence of increased cardiac toxicity as a reason for treatment termination.

QTc and psychopharmacs: are there any differences between monotherapy and polytherapy

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Sisek-Šprem Mirna

2007-05-01

Full Text Available Abstract Background Some psychotropic drugs are connected with prolongation of QT interval, increased risk of cardiac arrhythmias and greater incidence of sudden death, especially when used in combination. Concomitant use of antipsychotics and antidepressants is not rare in our clinical practice. The study compares the length of QT interval in patients on monotherapy with an antipsychotic or an antidepressant and patients taking polytherapy (an antipsychotic agent combined with an antidepressant. Methods Sixty-one hospitalized women who met the ICD-10 criteria for schizophrenia, schizoaffective psychosis, delusional disorder and mood disorder were included in the study. The monotherapy group was consisted of thirty-two women treated with an antipsychotic or an antidepressant while the polytherapy group was composed of twenty-nine women treated with an antipsychotic agent plus an antidepressant. Two electrocardiograms (ECGs were obtained for each patient: the first was carried out before the treatment and the second after two weeks of treatment. Statistical analysis was carried out by SPSS program and included unpaired and paired t test and Fisher's exact test. Results Mean baseline QTc values did not differ between the groups (439 ± 22 ms was the same value found in the both groups; unpaired t test, p > 0.5. Mean QTc intervals after two weeks of treatment were also similar (439 ± 24 ms in the monotherapy group and 440 ± 20 ms in the polytherapy group; unpaired t test, p > 0.5. Fisher's exact test did not reveal significant difference in the number of patients with borderline (451–470 ms or prolonged (> 470 ms QTc between groups, neither before treatment nor after two weeks of treatment. Twenty two women of the total of sixty one patients (36% had QTc > 450 ms before applying therapy. Conclusion We did not find significant QT prolongation in our patients after two weeks of treatment with antipsychotics and/or antidepressants. The QTc

Kombinationsbehandling med fluconazol og andre QTc-forlængende lægemidler forlænger QTc- intervallet

DEFF Research Database (Denmark)

Buch, Tina; Andersen, Stig Ejdrup

2015-01-01

Several drugs have a QTc-prolonging effect and are metabolized by CYP3A4. The combination of QTc-prolonging drugs may act additive of the QTc interval. The risk increases additionally by co-administration of a CYP3A4-inhibiting substrate. This case report describes an incident with QTc prolongati...... which was probably caused by an interaction induced by a combination of amiodarone, clarithromycin and the CYP3A4-inhibitor fluconazole....

QTc interval in the assessment of cardiac risk

DEFF Research Database (Denmark)

Elming, Hanne; Brendorp, Bente; Køber, Lars

2002-01-01

importance in hypertrophic cardiomyopathy or in the arrhythmogenic right ventricular disease. The degree of QTc prolonging during treatment with QTc prolonging drugs is prognostic for the risk of ventricular arrhythmia in form of torsade de pointes and QTc prolonging drugs should probably not be prescribed...... for patients with a QTc greater than 460 ms and withdrawn if QTc exceeds 500 ms during treatment. Data from the DIAMOND study suggest that QTc can be used to point out those heart failure patients who will benefit from antiarrhythmic therapy....

Scientific white paper on concentration-QTc modeling.

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Garnett, Christine; Bonate, Peter L; Dang, Qianyu; Ferber, Georg; Huang, Dalong; Liu, Jiang; Mehrotra, Devan; Riley, Steve; Sager, Philip; Tornoe, Christoffer; Wang, Yaning

2018-06-01

The International Council for Harmonisation revised the E14 guideline through the questions and answers process to allow concentration-QTc (C-QTc) modeling to be used as the primary analysis for assessing the QTc interval prolongation risk of new drugs. A well-designed and conducted QTc assessment based on C-QTc modeling in early phase 1 studies can be an alternative approach to a thorough QT study for some drugs to reliably exclude clinically relevant QTc effects. This white paper provides recommendations on how to plan and conduct a definitive QTc assessment of a drug using C-QTc modeling in early phase clinical pharmacology and thorough QT studies. Topics included are: important study design features in a phase 1 study; modeling objectives and approach; exploratory plots; the pre-specified linear mixed effects model; general principles for model development and evaluation; and expectations for modeling analysis plans and reports. The recommendations are based on current best modeling practices, scientific literature and personal experiences of the authors. These recommendations are expected to evolve as their implementation during drug development provides additional data and with advances in analytical methodology.

Long QTc Syndrome Type 2 Presenting in a Postpartum Patient on Medroxyprogesterone

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John Kern

2014-01-01

Full Text Available Introduction. Congenital long QT syndrome type 2 (LQTS2 is a rare inherited cardiac abnormality resulting in increased risk of polymorphic ventricular tachycardia (PVT. Case Description. A 21-year-old postpartum female presented with syncopal episode after phone alarm. She was noted to have PVT on telemetry monitoring in the emergency department. EKG revealed QTc of 530. The patient’s only medication was medroxyprogesterone. She ultimately received a dual chamber pacemaker with ICD. Discussion. LQTS2 is associated with alarm sounds as a precipitating factor. Postpartum hormonal shifts as well as medroxyprogesterone have significant effect on native QTc duration.

Incidence and risk of QTc interval prolongation among cancer patients treated with vandetanib: a systematic review and meta-analysis.

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Jiajie Zang

Full Text Available Vandetanib is a multikinase inhibitor that is under assessment for the treatment of various cancers. QTc interval prolongation is one of the major adverse effects of this drug, but the reported incidence varies substantially among clinical trials. We performed a systematic review and meta-analysis to obtain a better understanding in the risk of QTc interval prolongation among cancer patients administered vandetanib.Eligible studies were phase II and III prospective clinical trials that involved cancer patients who were prescribed vandetanib 300 mg/d and that included data on QTc interval prolongation. The overall incidence and risk of QTc interval prolongation were calculated using random-effects or fixed-effects models, depending on the heterogeneity of the included studies. Nine trials with 2,188 patients were included for the meta-analysis. The overall incidence of all-grade and high-grade QTc interval prolongation was 16.4% (95% CI, 8.1-30.4% and 3.7% (8.1-30.4%, respectively, among non-thyroid cancer patients, and 18.0% (10.7-28.6% and 12.0% (4.5-28.0%, respectively, among thyroid cancer patients. Patients with thyroid cancer who had longer treatment duration also had a higher incidence of high-grade events, with a relative risk of 3.24 (1.57-6.71, than patients who had non-thyroid cancer. Vandetanib was associated with a significantly increased risk of all-grade QTc interval prolongation with overall Peto odds ratios of 7.26 (4.36-12.09 and 5.70 (3.09-10.53 among patients with non-thyroid cancer and thyroid cancer, respectively, compared to the controls.Treatment with vandetanib is associated with a significant increase in the overall incidence and risk of QTc interval prolongation. Different cancer types and treatment durations may affect the risk of developing high-grade QTc interval prolongation.

Prognostic value of QTc interval dispersion changes during exercise testing in hypertensive men

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Đorđević Dragan

2008-01-01

Full Text Available INTRODUCTION The prognostic significance of QTc dispersion changes during exercise testing (ET in patients with left ventricular hypertrophy is not clear. OBJECTIVE The aim was to study the dynamics of QTc interval dispersion (QTcd in patients (pts with left ventricular hypertrophy (LVH during the exercise testing and its prognostic significance. METHOD In the study we included 55 men (aged 53 years with hypertensive left ventricular hypertrophy and a negative ET (LVH group, 20 men (aged 58 years with a positive ET and 20 healthy men (aged 55 years. There was no statistically significant difference in the left ventricular mass index (LVMI between LVH group and ILVH group (160.9±14.9 g/m2 and 152.8±22.7 g/m2. The first ECG was done before the ET and the second one was done during the first minute of recovery, with calculation of QTc dispersion. The patients were followed during five years for new cardiovascular events. RESULTS During the ET, the QTcd significantly increased in LVH group (56.8±18.0 - 76.7±22.6 ms; p<0.001. A statistically significant correlation was found between the amount of ST segment depression at the end of ET and QTc dispersion at the beginning and at the end of ET (r=0.673 and r=0.698; p<0.01. The QTc dispersion was increased in 35 (63.6% patients and decreased in 20 (36.4% patients during the ET. Three patients (5.4% in the first group had adverse cardiovascular events during the five-year follow-up. A multiple stepwise regression model was formed by including age, LVMI, QTc interval, QTc dispersion and change of QTc dispersion during the ET. There was no prognostic significance of QTc interval and QTc dispersion during five-year follow-up in regard to adverse cardiovascular events, but prognostic value was found for LVMI (coefficient β=0.480; p<0.001. CONCLUSION The increase of QTc interval dispersion is common in men with positive ET for myocardial ischemia and there is a correlation between QTc dispersion and

Haloperidol

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Haloperidol is used to treat psychotic disorders (conditions that cause difficulty telling the difference between things or ... and things or ideas that are not real). Haloperidol is also used to control motor tics (uncontrollable ...

Risk factors for QTc interval prolongation

NARCIS (Netherlands)

Heemskerk, Charlotte P.M.; Pereboom, Marieke; van Stralen, Karlijn; Berger, Florine A.; van den Bemt, Patricia M.L.A.; Kuijper, Aaf F.M.; van der Hoeven, Ruud T M; Mantel-Teeuwisse, Aukje K.; Becker, Matthijs L

2018-01-01

Purpose: Prolongation of the QTc interval may result in Torsade de Pointes, a ventricular arrhythmia. Numerous risk factors for QTc interval prolongation have been described, including the use of certain drugs. In clinical practice, there is much debate about the management of the risks involved. In

Haloperidol versus second-generation antipsychotics in the long-term treatment of schizophrenia.

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Buoli, Massimiliano; Kahn, René S; Serati, Marta; Altamura, A Carlo; Cahn, Wiepke

2016-07-01

The purpose of the study was to compare antipsychotic monotherapies in terms of time to discontinuation in a sample of schizophrenia patients followed-up for 36 months. Two hundred and twenty schizophrenia patients, treated with antipsychotic monotherapy and followed-up in psychiatric outpatient clinics of Universities of Milan and Utrecht were included in the study. A survival analysis (Kaplan-Meier) of the 36-month follow-up period was performed to compare the single treatment groups. End-point was considered as discontinuation of treatment for recurrence, side effects or non-compliance. Patients treated with haloperidol discontinued more than the other groups (Breslow: risperidone p haloperidol group than in the olanzapine group (p haloperidol group than with olanzapine (p haloperidol. In addition, atypical antipsychotics seem to be more protective against recurrences than haloperidol. However, these results should be cautiously interpreted in the light of potential confounder factors such as duration of illness. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Evaluasi Elektrokardiogram Interval QTc dan JTc pada Penderita Malaria Vivaks yang Diberikan Dihidroartemisinin-Piperakuin dan Primakuin

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Jason Sriwijaya

2016-03-01

Full Text Available Dihidroartemisinin-piperakuin (DHA-PPQ telah digunakan secara global sebagai terapi malaria vivaks. Salah satu efek samping DHA-PPQ adalah pemanjangan repolarisasi ventrikel yang dapat menimbulkanaritmia ventrikuler yaitu Torsade de Pointes (TdP. Studi before-after ini bertujuan untuk mengetahuiperbedaan rerata interval QTc dan JTc penderita malaria vivaks sebelum dan sesudah pemberian DHA-PPQdan primakuin (PQ. Penelitian dilakukan di Lembaga Biologi Molekuler Eijkman, Jakarta pada bulan Mei-Juli2015. Sumber data adalah data sekunder hasil rekaman EKG pada penelitian utama “Safety, tolerability, andefficacy of artesunat-pyonaridine or dihydroartemisinin-piperaquine in combination with primaquine as radicalcure for P.vivax in Indonesian soldiers” tahun 2010. Subyek yang masuk kriteria seleksi pada pemberianDHA-PPQ dan PQ, masing-masing berjumlah 24 subyek dan 14 subyek. Interval QT dan JT dalam penelitianini menggunakan dua formula yang sudah dikoreksi terhadap frekuensi denyut jantung yaitu formula Bazett(QTcB, JTcB dan Fridericia (QTcF, JTcF. Pemberian DHA-PPQ menunjukkan pemanjangan rerata intervalQTcF secara bermakna dibandingkan baseline yaitu sebesar 14,42 milidetik terjadi di D3 predose dan 20,53milidetik di D3 postdose. Rerata pemanjangan interval JTcF setelah pemberian DHA-PPQ adalah 13,43milidetik di D3 postdose. Pada pemberian PQ terdapat perbedaan nilai rerata interval QTcB dibandingkanbaseline sebesar 19,42 milidetik. Rerata pemanjangan interval JTcF dibandingkan baseline 16,50 milidetik diD42 postdose dan secara statistik bermakna. Kata kunci: dihidroartemisinin-piperakuin, primakuin, malaria vivaks, Torsade de Pointes, interval QTc, interval JTc.   Electrocardiogram Evaluation of QTc and JTc Interval of DihydroartemisininPiperaquine and Primaquine Therapies Given to The Vivax Malaria Patients Abstract Dihydroartemisinin-piperaquin (DHA-PPQ has been used globally as standard combination therapies for vivax malaria treatment

Rapid tranquilization for agitated patients in emergency psychiatric rooms: a randomized trial of olanzapine, ziprasidone, haloperidol plus promethazine, haloperidol plus midazolam and haloperidol alone

OpenAIRE

Baldaçara,Leonardo; Sanches,Marsal; Cordeiro,Daniel Cruz; Jackowski,Andrea Parolin

2011-01-01

OBJECTIVE: To compare the effectiveness of intramuscular olanzapine, ziprasidone, haloperidol plus promethazine, haloperidol plus midazolam and haloperidol alone as the first medication(s) used to treat patients with agitation and aggressive behavior. METHOD: One hundred fifty patients with agitation caused by psychotic or bipolar disorder were randomly assigned under double-blind conditions to receive olanzapine, ziprasidone, haloperidol plus midazolam, haloperidol plus promethazine or halop...

Radioimmunoassay of haloperidol in human serum: correlation of serum haloperidol with serum prolactin

International Nuclear Information System (INIS)

Poland, R.E.; Rubin, R.T.

1981-01-01

A radioimmunoassay (RIA) for measurement of serum haloperidol is described. Compared to gaschromatography (GC), RIA vaues average 40% higher. However, a simple organic extraction of serum yields statistically equivalent RIA and GC haloperidol determinations. For both men and women combined, there was a positive correlation between dose (mg/kg/day) and steady-state serum haloperidol level (r = +0.86) and between steady-state serum haloperidol and serum prolactin (PRL) concentration

Effect of QTc interval on prediction of hypotension following subarachnoid block in patients undergoing cesarean section: A comparative study

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Sampa Dutta Gupta

2012-01-01

Full Text Available Background: Previous studies have revealed that QTc interval is prolonged in pre-eclamptic parturients. Another study reflected the relationship between the sympathetic block and QTc interval. Subarachnoid block was safely administered in patients with severe pre-eclampsia. It has also been noticed that hypotension in response to spinal anesthesia is relatively less in pre-eclamptic patients than normal parturients. Aim: To compare the QTc values in normal and pre-eclamptic term parturients and to establish whether any correlation exists between the QTc interval and the systemic hypotension following subarachnoid block. Materials and Methods: Twenty-five pre-eclamptic patients (Group A and 25 normotensive patients (Group B were included in this study. QTc interval was recorded for each patient before subarachnoid block for cesarean section. Changes in arterial blood pressure and heart rate were measured in both the groups and compared. Results: Baseline QTc was significantly higher in the pre-eclamptic group (Group A: 0.47 ± 0.11 with that of control (Group B: 0.36. ± 0.02. Significant fall in blood pressure was seen only in one group with QTc between 0.38 and 0.39 in Group A. Hypotension was significantly more in normotensive mothers (Group B. However, no statistical correlation could be drawn from this study between QTc interval and hypotension, although a trend toward increasing hypotension with decreasing QTc was present. Discussion : The prolonged QTc intervals seen in pre-eclamptic patients may be due to the contributory effects of sympathetic hyperactivity, hypertension, and hypocalcemia secondary to underlying vasoconstriction. Decreased vagal control of heart in pre-eclampsia may have produced the difference in change in hemodynamic status between pre-eclamptic and normotensive parturient. Conclusion: Any consistent correlation between QTc and hypotension following subarachnoid block could not be derived from this study. To achieve a

A double-blind comparative multicentre study of remoxipride and haloperidol in schizophrenia.

Science.gov (United States)

Lindström, L H; Wieselgren, I M; Struwe, G; Kristjansson, E; Akselson, S; Arthur, H; Andersen, T; Lindgren, S; Norman, O; Naimell, L

1990-01-01

In a double-blind multicentre study of parallel group design the efficacy and safety of remoxipride and haloperidol were compared in a total of 96 patients with acute episodes of schizophrenic or schizophreniform disorder according to DSM-III. There were 48 patients in each treatment group; 27 men and 21 women in the remoxipride group, 33 men and 15 women in the haloperidol group. The median duration of illness was 7 years in both groups. The mean daily dose was 437 mg for remoxipride and 10.6 mg for haloperidol during the last week of treatment. No statistically significant differences in total BPRS scores were found between remoxipride and haloperidol. The median total BPRS scores at the start of active treatment were 26 in the remoxipride and 27 in the haloperidol group; these were reduced to 16 and 12.5, respectively, at the last rating. According to Clinical Global Impression (CGI), 43% of patients in the remoxipride group and 68% of those in the haloperidol group improved much or very much during treatment. This difference was not statistically significant. Treatment-emergent extrapyramidal side effects such as akathisia, tremor, and rigidity occurred significantly more frequently in the haloperidol group; this group also made more frequent use of anticholinergic drugs. Neither of the trial drugs seriously affected laboratory or cardiovascular variables. It is concluded that remoxipride has an antipsychotic effect in a dose range of 150-600 mg per day comparable to that of haloperidol in doses up to 20 mg per day but with fewer extrapyramidal side effects.

Effects of Cannabis sativa extract on haloperidol-induced catalepsy and oxidative stress in the mice

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Abdel-Salam, Omar M.E.; El-Sayed El-Shamarka, Marawa; Salem, Neveen A.; El-Din M. Gaafar, Alaa

2012-01-01

Haloperidol is a classic antipsychotic drug known for its propensity to cause extrapyramidal symptoms due to blockade of dopamine D2 receptors in the striatum. Interest in medicinal uses of cannabis is growing. Cannabis sativa has been suggested as a possible adjunctive in treatment of Parkinson's disease. The present study aimed to investigate the effect of repeated administration of an extract of Cannabis sativa on catalepsy and brain oxidative stress induced by haloperidol administration in mice. Cannabis extract was given by subcutaneous route at 5, 10 or 20 mg/kg (expressed as Δ9-tetrahydrocannabinol) once daily for 18 days and the effect on haloperidol (1 mg/kg, i.p.)-induced catalepsy was examined at selected time intervals using the bar test. Mice were euthanized 18 days after starting cannabis injection when biochemical assays were carried out. Malondialdehyde (MDA), reduced glutathione (GSH) and nitric oxide (the concentrations of nitrite/nitrate) were determined in brain and liver. In saline-treated mice, no catalepsy was observed at doses of cannabis up to 20 mg/kg. Mice treated with haloperidol at the dose of 1 mg/kg, exhibited significant cataleptic response. Mice treated with cannabis and haloperidol showed significant decrease in catalepsy duration, compared with the haloperidol only treated group. This decrease in catalepsy duration was evident on days 1-12 after starting cannabis injection. Later the effect of cannabis was not apparent. The administration of only cannabis (10 or 20 mg/kg) decreased brain MDA by 17.5 and 21.8 %, respectively. The level of nitric oxide decreased by 18 % after cannabis at 20 mg/kg. Glucose in brain decreased by 20.1 % after 20 mg/kg of cannabis extract. The administration of only haloperidol increased MDA (22.2 %), decreased GSH (25.7 %) and increased brain nitric oxide by 44.1 %. The administration of cannabis (10 or 20 mg/kg) to haloperidol-treated mice resulted in a significant decrease in brain MDA and nitric

Compound list: haloperidol [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available haloperidol HPL 00036 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/haloperidol....Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/haloperidol....Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Single/haloperidol...archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/haloperidol.Rat.in_vivo.Liver.Repeat.zip ...

QTc prolongation in Black diabetic subjects with cardiac autonomic ...

African Journals Online (AJOL)

ed QT (QTc) in diabetic individuals with cardiac auto- .... standing compared to the R-R at the 15th beat (30:15) was calculated. Abnormal .... tion between QTc and age (Pearson's univariate analysis r=0.080 ..... Diagnosis and management of.

Efficacy and safety of haloperidol for in-hospital delirium prevention and treatment: A systematic review of current evidence.

Science.gov (United States)

Schrijver, E J M; de Graaf, K; de Vries, O J; Maier, A B; Nanayakkara, P W B

2016-01-01

Haloperidol is generally considered the drug of choice for in-hospital delirium management. We conducted a systematic review to evaluate the evidence for the efficacy and safety of haloperidol for the prevention and treatment of delirium in hospitalized patients. PubMed, Embase, Cumulative Index to Nursing and Allied Health (CINAHL), PsycINFO, and the Cochrane Library were systematically searched up to April 21, 2015. We included English full-text randomized controlled trials using haloperidol for the prevention or treatment of delirium in adult hospitalized patients reporting on delirium incidence, duration, or severity as primary outcome. Quality of evidence was graded. Meta-analysis was not conducted because of between-study heterogeneity. Twelve studies met our inclusion criteria, four prevention and eight treatment trials. Methodological limitations decreased the graded quality of included studies. Results from placebo-controlled prevention studies suggest a haloperidol-induced protective effect for delirium in older patients scheduled for surgery: two studies reported a significant reduction in ICU delirium incidence and one study found a significant reduction in delirium severity and duration. Although placebo-controlled trials are missing, pharmacological treatment of established delirium reduced symptom severity. Haloperidol administration was not associated with treatment-limiting side-effects, but few studies used a systematic approach to identify adverse events. Although results on haloperidol for delirium management seem promising, current prevention trials lack external validity and treatment trials did not include a placebo arm on top of standard nonpharmacological care. We therefore conclude that the current use of haloperidol for in-hospital delirium is not based on robust and generalizable evidence. Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Are ECG monitoring recommendations before prescription of QT-prolonging drugs applied in daily practice?

DEFF Research Database (Denmark)

Warnier, Miriam Jacoba; Rutten, Frans Hendrik; Souverein, Patrick Cyriel

2015-01-01

PURPOSE: Monitoring of the QT duration by electrocardiography (ECG) prior to treatment is frequently recommended in the label of QT-prolonging drugs. It is, however, unknown how often general practitioners in daily clinical practice are adhering to these risk-minimization measures. We assessed...... the frequency of ECG measurements in patients where haloperidol was initiated in primary care. METHODS: Patients (≥18 years) with a first prescription of haloperidol in the UK Clinical Practice Research Datalink (2009-2013) were included. The proportion of ECGs made was determined in two blocks of 4 weeks......: during the exposure period when haloperidol was initiated, and during the control period, 1 year before. Conditional logistic regression analysis was applied to calculate the relative risk of having an ECG in the exposure period compared with the control period. Subgroup analyses were performed to assess...

Increased QTc dispersion is related to blunted circadian blood pressure variation in normoalbuminuric type 1 diabetic patients

DEFF Research Database (Denmark)

Poulsen, P L; Ebbehøj, E; Arildsen, H

2001-01-01

. The association between QTc dispersion and diastolic night BP persisted after controlling for potential confounders such as sex, age, duration of diabetes, urinary albumin excretion, and HbA1c. Power spectral analysis suggested an altered sympathovagal balance in patients with QTc dispersion above the median...... (ratio of low-frequency/high-frequency power: 1.0 vs. 0.85, P fall in BP and an altered sympathovagal balance. This coexistence may be operative in the ability of these parameters......A reduced nocturnal fall in blood pressure (BP) and increased QT dispersion both predict an increased risk of cardiovascular events in diabetic as well as nondiabetic subjects. The relationship between these two parameters remains unclear. The role of diabetic autonomic neuropathy in both QT...

Haloperidol increases false recognition memory of thematically related pictures in healthy volunteers.

Science.gov (United States)

Guarnieri, Regina V; Buratto, Luciano G; Gomes, Carlos F A; Ribeiro, Rafaela L; de Souza, Altay A Lino; Stein, Lilian M; Galduróz, José C; Bueno, Orlando F A

2017-01-01

Dopamine can modulate long-term episodic memory. Its potential role on the generation of false memories, however, is less well known. In a randomized, double-blind, placebo-controlled experiment, 24 young healthy volunteers ingested a 4-mg oral dose of haloperidol, a dopamine D 2 -receptor antagonist, or placebo, before taking part in a recognition memory task. Haloperidol was active during both study and test phases of the experiment. Participants in the haloperidol group produced more false recognition responses than those in the placebo group, despite similar levels of correct recognition. These findings show that dopamine blockade in healthy volunteers can specifically increase false recognition memory. Copyright © 2016 John Wiley & Sons, Ltd.

Invariom based electron density studies on the C/Si analogues haloperidol/sila-haloperidol and venlafaxine/sila-venlafaxine.

Science.gov (United States)

Luger, Peter; Dittrich, Birger; Tacke, Reinhold

2015-09-14

The subjects of this study are the structures and electron densities of the carbon/silicon analogues haloperidol/sila-haloperidol (1a/1b) and venlafaxine/sila-venlafaxine (2a/2b). The parent carbon compounds 1a (an antipsychotic agent) and 2a (an antidepressant) are both in clinical use. For haloperidol/sila-haloperidol, three published structures were studied in more detail: the structures of haloperidol hydrochloride (1a·HCl), haloperidol hydropicrate (1a·HPic) and sila-haloperidol hydrochloride (1b·HCl). For venlafaxine/sila-venlafaxine, the published structures of venlafaxine (2a), venlafaxine hydrochloride (2a·HCl; as orthorhombic (2a·HCl-ortho) and monoclinic polymorph (2a·HCl-mono)) and sila-venlafaxine hydrochloride (2b·HCl) were investigated. Based on these structures, the molecular electron densities were reconstructed by using the invariom formalism. They were further analysed in terms of Bader's quantum theory of atoms in molecules, electrostatic potentials mapped onto electron density isosurfaces and Hirshfeld surfaces. These studies were performed with a special emphasis on the comparison of the corresponding carbon/silicon analogues.

Food and Insulin Effect on QT/QTC Interval of ECG

Science.gov (United States)

2014-08-19

Effects of Different Meals on the QT/QTc Interval; Insulin and Oral Hypoglycemic [Antidiabetic] Drugs Causing Adverse Effects in Therapeutic Use; C-Peptide Effects on the QT/QTc Interval; Moxifloxacin ECG Profile in Fed and Fasted State; Japanese vs. Caucasian TQT Comparison

QTc-prolonging drugs and hospitalizations for cardiac arrhythmias

DEFF Research Database (Denmark)

De Bruin, Marie L; Hoes, Arno W; Leufkens, Hubert G M

2003-01-01

Cardiac arrhythmia as an adverse effect of noncardiac drugs has been an issue of growing importance during the past few years. In this population-based study, we evaluated the risk for serious cardiac arrhythmias during the use of several noncardiac QTc-prolonging drugs in day-to-day practice......, and subsequently focused on several specific groups of patients who could be extremely vulnerable for drug-induced arrhythmias. We performed a case-control study in which patients (cases), hospitalized for nonatrial cardiac arrhythmias from 1987 to 1998, were compared with their matched controls regarding current...... use of QTc-prolonging drugs. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariate conditional logistic regression, adjusting for potential confounding factors. Data were obtained from the PHARMO record linkage system. We identified 501 cases, 39 of whom used QTc...

Uremic retention solute indoxyl sulfate level is associated with prolonged QTc interval in early CKD patients.

Directory of Open Access Journals (Sweden)

Wei-Hua Tang

Full Text Available Total mortality and sudden cardiac death is highly prevalent in patients with chronic kidney disease (CKD. In CKD patients, the protein-bound uremic retention solute indoxyl sulfate (IS is independently associated with cardiovascular disease. However, the underlying mechanisms of this association have yet to be elucidated. The relationship between IS and cardiac electrocardiographic parameters was investigated in a prospective observational study among early CKD patients. IS arrhythmogenic effect was evaluated by in vitro cardiomyocyte electrophysiological study and mathematical computer simulation. In a cohort of 100 early CKD patients, patients with corrected QT (QTc prolongation had higher IS levels. Furthermore, serum IS level was independently associated with prolonged QTc interval. In vitro, the delay rectifier potassium current (IK was found to be significantly decreased after the treatment of IS in a dose-dependent manner. The modulation of IS to the IK was through the regulation of the major potassium ion channel protein Kv 2.1 phosphorylation. In a computer simulation, the decrease of IK by IS could prolong the action potential duration (APD and induce early afterdepolarization, which is known to be a trigger mechanism of lethal ventricular arrhythmias. In conclusion, serum IS level is independently associated with the prolonged QTc interval in early CKD patients. IS down-regulated IK channel protein phosphorylation and the IK current activity that in turn increased the cardiomyocyte APD and QTc interval in vitro and in the computer ORd model. These findings suggest that IS may play a role in the development of arrhythmogenesis in CKD patients.

3H and 125I radioimmunoassays of haloperidol compared with fluoroimmunoassay involving antibody coupled to magnetizable solid phase

International Nuclear Information System (INIS)

Rowell, F.J.; Hui, S.M.; Kamel, S.R.

1981-01-01

Radioimmunoassays for haloperidol are described, involving use of tritium-or 125 I-labeled drug or tritium-labeled spiroperidol, and a rabbit antiserum to a drug/bovine serum albumin conjugate. The 125 I-labeled drug was prepared by the Chloramine T iodination technique. A fluoroimmunoassay for haloperidol is also described in which the antiserum is coupled to magnetizable solid-phase medium, and fluorescein-labeled haloperidol is used. The assays have acceptable accuracy, precision, and reproducibility, and are specific for haloperidol and similar butyrophenones, with no significant interference from known metabolites and other drugs. Only the radioimmunoassays have sufficient sensitivity to cover the whole range of haloperidol concentrations in serum. The fluoroimmunoassay can be used to monitor high concentrations of haloperidol in 150 μL samples or the complete concentration range of 1-mL serum samples that are extracted and concentrated before assay

3H and 125I radioimmunoassays of haloperidol compared with fluoroimmunoassay involving antibody coupled to magnetizable solid phase

International Nuclear Information System (INIS)

Rowell, F.J.; Hui, S.M.; Kamel, S.R.

1981-01-01

Radioimmunoassays for haloperidol are described, involving use of tritium- or 125I-labeled drug or tritium-labeled spiroperidol, and a rabbit antiserum to a drug/bovine serum albumin conjugate. The 125I-labeled drug was prepared by the Chloramine T iodination technique. A fluoroimmunoassay for haloperidol is also described in which the antiserum is coupled to magnetizable solid-phase medium, and fluorescein-labeled haloperidol is used. The assays have acceptable accuracy, precision, and reproducibility, and are specific for haloperidol and similar butyrophenones, with no significant interference from known metabolites and other drugs. Only the radioimmunoassays have sufficient sensitivity to cover the whole range of haloperidol concentrations in serum. The fluoroimmunoassay can be used to monitor high concentrations of haloperidol in 150-microL samples or the complete concentration range of 1-mL serum samples that are extracted and concentrated before assay

Prolonged Q-T(c) interval in mild portal hypertensive cirrhosis

DEFF Research Database (Denmark)

Ytting, Henriette; Henriksen, Jens Henrik; Fuglsang, Stefan

2005-01-01

BACKGROUND/AIMS: The Q-T(c) interval is prolonged in a substantial fraction of patients with cirrhosis, thus indicating delayed repolarisation. However, no information is available in mild portal hypertensive patients. We therefore determined the Q-T(c) interval in cirrhotic patients with hepatic...... venous pressure gradient (HVPG) portal hypertension (HVPG> or = 12 mmHg) and controls without liver disease. RESULTS......), values which are significantly above that of the controls (0.410 s(1/2), P portal hypertensive group, the Q-T(c) interval was inversely related to indicators of liver function, such as indocyanine green clearance (r = -0.34, P

Effect of Lorazepam With Haloperidol vs Haloperidol Alone on Agitated Delirium in Patients With Advanced Cancer Receiving Palliative Care

Science.gov (United States)

Hui, David; Frisbee-Hume, Susan; Wilson, Annie; Dibaj, Seyedeh S.; Nguyen, Thuc; De La Cruz, Maxine; Walker, Paul; Zhukovsky, Donna S.; Delgado-Guay, Marvin; Vidal, Marieberta; Epner, Daniel; Reddy, Akhila; Tanco, Kimerson; Williams, Janet; Hall, Stacy; Liu, Diane; Hess, Kenneth; Amin, Sapna; Breitbart, William; Bruera, Eduardo

2017-01-01

IMPORTANCE The use of benzodiazepines to control agitation in delirium in the last days of life is controversial. OBJECTIVE To compare the effect of lorazepam vs placebo as an adjuvant to haloperidol for persistent agitation in patients with delirium in the setting of advanced cancer. DESIGN, SETTING, AND PARTICIPANTS Single-center, double-blind, parallel-group, randomized clinical trial conducted at an acute palliative care unit at MD Anderson Cancer Center, Texas, enrolling 93 patients with advanced cancer and agitated delirium despite scheduled haloperidol from February 11, 2014, to June 30, 2016, with data collection completed in October 2016. INTERVENTIONS Lorazepam (3 mg) intravenously (n = 47) or placebo (n = 43) in addition to haloperidol (2 mg) intravenously upon the onset of an agitation episode. MAIN OUTCOMES AND MEASURES The primary outcome was change in Richmond Agitation-Sedation Scale (RASS) score (range, −5 [unarousable] to 4 [very agitated or combative]) from baseline to 8 hours after treatment administration. Secondary end points were rescue neuroleptic use, delirium recall, comfort (perceived by caregivers and nurses), communication capacity, delirium severity, adverse effects, discharge outcomes, and overall survival. RESULTS Among 90 randomized patients (mean age, 62 years; women, 42 [47%]), 58 (64%) received the study medication and 52 (90%) completed the trial. Lorazepam + haloperidol resulted in a significantly greater reduction of RASS score at 8 hours (−4.1 points) than placebo + haloperidol (−2.3 points) (mean difference, −1.9 points [95% CI, −2.8 to −0.9]; P haloperidol group required less median rescue neuroleptics (2.0 mg) than the placebo + haloperidol group (4.0 mg) (median difference, −1.0 mg [95% CI, −2.0 to 0]; P = .009) and was perceived to be more comfortable by both blinded caregivers and nurses (caregivers: 84% for the lorazepam + haloperidol group vs 37% for the placebo + haloperidol group; mean difference, 47

Effect of Average Annual Mean Serum Ferritin Levels on QTc Interval and QTc Dispersion in Beta-Thalassemia Major

Directory of Open Access Journals (Sweden)

Yazdan Ghandi

2017-08-01

Full Text Available Background There is evidence indicating impaired cardiomyocytic contractility, delayed electrical conduction and increased electrophysiological heterogeneities due to iron toxicity in beta-thalassemia major patients. In the present study, we compared the electrocardiographic and echocardiographic features of beta-thalassemia major patients with a healthy control group. Materials and Methods The average annual serum ferritin levels of fifty beta-thalassemia major patients were assessed. For each patient, corrected QT (QTc intervals and QTc dispersions (QTcd were calculated and V1S and V5R were measured. All subjects underwent two-dimensional M-mode echocardiography and Doppler study and were compared with 50 healthy subjects as a control group. Results QTc interval and dispersion were significantly higher in beta-thalassemia major patients (P= 0.001. The mean V5R (20.04 ± 4.34 vs. 17.14 ± 2.55 mm and V1S (10.24 ± 2.62 vs. 7.83 ± 0.38 mm showed considerably higher mean values in patients in comparison with control group.Peak mitral inflow velocity at early diastole and early to late ratio in the case- group was markedly higher(P

Parkinson’s Disease: Low-Dose Haloperidol Increases Dopamine Receptor Sensitivity and Clinical Response

Directory of Open Access Journals (Sweden)

Craig J. Hudson

2014-01-01

Full Text Available Background. It is known that ultra-low doses of haloperidol can cause dopamine supersensitivity of dopamine D2 receptors and related behaviour in animals. Objective. The objective was to determine whether a daily ultra-low dose of 40 micrograms of haloperidol could enhance the clinical action of levodopa in Parkinson’s disease patients. Method. While continuing their daily treatment with levodopa, 16 patients with Parkinson’s disease were followed weekly for six weeks. They received an add-on daily dose of 40 micrograms of haloperidol for the first two weeks only. The SPES/SCOPA scale (short scale for assessment of motor impairments and disabilities in Parkinson’s disease was administered before treatment and weekly throughout the trial. Results. The results showed a mean decrease in SPES/SCOPA scores after one week of the add-on treatment. Conclusion. SCOPA scores decreased after the addition of low-dose haloperidol to the standard daily levodopa dose. This finding is consistent with an increase in sensitivity of dopamine D2 receptors induced by haloperidol. Such treatment for Parkinson’s disease may possibly permit the levodopa dose to be reduced and, thus, delay the onset of levodopa side effects.

Effects of a screening and treatment protocol with haloperidol on post-cardiotomy delirium: a prospective cohort study†

Science.gov (United States)

Schrøder Pedersen, Sofie; Kirkegaard, Thomas; Balslev Jørgensen, Martin; Lind Jørgensen, Vibeke

2014-01-01

OBJECTIVES Post-cardiotomy delirium is common and associated with increased morbidity and mortality. No gold standard exists for detecting delirium, and evidence to support the choice of treatment is needed. Haloperidol is widely used for treating delirium, but indication, doses and therapeutic targets vary. Moreover, doubt has been raised regarding overall efficacy. The purpose of this study was to assess the effect of a combination of early detection and standardized treatment with haloperidol on post-cardiotomy delirium, with the hypothesis that the proportion of delirium- and coma-free days could be increased. Length of stay (LOS), complications and 180-day mortality are reported. METHODS Prospective interventional cohort study. One hundred and seventeen adult patients undergoing cardiac surgery were included before introduction of a screening and treatment protocol with haloperidol for delirium, and 123 patients were included after. Nurses screened patients using validated tools (the Delirium Observation Screening (DOS) scale and confusion assessment method for the intensive care unit (CAM-ICU)). In case of delirium, a checklist to eliminate precipitating/ inducing factors and a protocol for standardized dosing with haloperidol was applied. Group comparison was done using non-parametric tests and analysis of fractions, and associations between delirium and predefined covariates were analysed with logistic regression. RESULTS Incidence of delirium after cardiac surgery was 21 (14–29) and 22 (15–30) %, onset was on postoperative day 1 (1–4) and 1 (1–3), duration was 1 (1–4) day and 3 (1–5) days, respectively, with no significant difference (Period 1 vs 2, all values are given as the median and 95% confidence interval). The proportion of delirium- and coma-free days was 67 (61–73) and 65 (60–70) %, respectively (ns). There was no difference in LOS or complication rate. Delirium was associated to increasing age, increased length of stay and

Palbociclib has no clinically relevant effect on the QTc interval in patients with advanced breast cancer.

Science.gov (United States)

Durairaj, Chandrasekar; Ruiz-Garcia, Ana; Gauthier, Eric R; Huang, Xin; Lu, Dongrui R; Hoffman, Justin T; Finn, Richard S; Joy, Anil A; Ettl, Johannes; Rugo, Hope S; Zheng, Jenny; Wilner, Keith D; Wang, Diane D

2018-03-01

The aim of this study was to assess the potential effects of palbociclib in combination with letrozole on QTc. PALOMA-2, a phase 3, randomized, double-blind, placebo-controlled trial, compared palbociclib plus letrozole with placebo plus letrozole in postmenopausal women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. The study included a QTc evaluation substudy carried out as a definitive QT interval prolongation assessment for palbociclib. Time-matched triplicate ECGs were performed at 0, 2, 4, 6, and 8 h at baseline (Day 0) and on Cycle 1 Day 14. Additional ECGs were collected from all patients for safety monitoring. The QT interval was corrected for heart rate using Fridericia's correction (QTcF), Bazett's correction (QTcB), and a study-specific correction factor (QTcS). In total, 666 patients were randomized 2 : 1 to palbociclib plus letrozole or placebo plus letrozole. Of these, 125 patients were enrolled in the QTc evaluation substudy. No patients in the palbociclib plus letrozole arm of the substudy (N=77) had a maximum postbaseline QTcS or QTcF value of ≥ 480 ms, or a maximum increase from clock time-matched baseline for QTcS or QTcF values of ≥ 60 ms. The upper bounds of the one-sided 95% confidence interval for the mean change from time-matched baseline for QTcS, QTcF, and QTcB at all time points and at steady-state Cmax following repeated administration of 125 mg palbociclib were less than 10 ms. Palbociclib, when administered with letrozole at the recommended therapeutic dosing regimen, did not prolong the QT interval to a clinically relevant extent.

CB1 cannabinoid receptor-mediated anandamide signaling mechanisms of the inferior colliculus modulate the haloperidol-induced catalepsy.

Science.gov (United States)

Medeiros, P; de Freitas, R L; Silva, M O; Coimbra, N C; Melo-Thomas, L

2016-11-19

The inferior colliculus (IC), a midbrain structure that processes acoustic information of aversive nature, is distinguished from other auditory nuclei in the brainstem by its connections with structures of the motor system. Previous evidence relating the IC to motor behavior shows that glutamatergic and GABAergic mechanisms in the IC exert influence on systemic haloperidol-induced catalepsy. There is substantial evidence supporting a role played by the endocannabinoid system as a modulator of the glutamatergic neurotransmission, as well as the dopaminergic activity in the basal nuclei and therefore it may be considered as a potential pharmacological target for the treatment of movement disorders. The present study evaluated if the endocannabinoid system in the IC plays a role in the elaboration of systemic haloperidol-induced catalepsy. Male Wistar rats received intracollicular microinjection of either the endogenous cannabinoid anandamide (AEA) at different concentrations (5, 50 or 100pmol/0.2μl), the CB 1 cannabinoid receptor antagonist AM251 at 50, 100 or 200pmol/0.2μl or vehicle, followed by intraperitoneal (IP) administration of either haloperidol at 0.5 or 1mg/kg or physiological saline. Systemic injection of haloperidol at both doses (0.5 or 1mg/kg, IP) produced a cataleptic state, compared to vehicle/physiological saline-treated group, lasting 30 and 50min after systemic administration of the dopaminergic receptors non-selective antagonist. The midbrain microinjection of AEA at 50pmol/0.2μl increased the latency for stepping down from the horizontal bar after systemic administration of haloperidol. Moreover, the intracollicular administration of AEA at 50pmol/0.2μl was able to increase the duration of catalepsy as compared to AEA at 100pmol/0.2-μl-treated group. Intracollicular pretreatment with AM251 at the intermediate concentration (100pmol/0.2μl) was able to decrease the duration of catalepsy after systemic administration of haloperidol. However

Haloperidol plasma levels in relation to antimanic effect

DEFF Research Database (Denmark)

Gjerris, Annette; Bech, P.; Christensen, Christian Broen

2016-01-01

n the treatment of mania, lithium (Li) has been found in several controlled studies as clearly superior to placebo, but haloperidol, when compared to Li, seems to be faster acting, at least with regard to motor activity (Shopsin et al., 1975). Hence, haloperidol has increasingly been recommended...... as the antimanic drug of choice (Shaw, 1979). However, the recommended dose of haloperidol for mania varies extremely, from 4 mg to 100 mg daily (Hollister, 1978). The haloperidol dose required obviously depends on the severity of the manic state, but might also depend on the metabolism of the drug, which varies...... in different patients (Forsman, 1977). To our knowledge the relationship between plasma levels of haloperidol and antimanic effect has not been evaluated. In the present study we have measured plasma levels of haloperidol in manic patients treated with a fixed haloperidol dose and examined the relationship...

Levofloxacin-Induced QTc Prolongation Depends on the Time of Drug Administration

NARCIS (Netherlands)

Kervezee, L; Gotta, V; Stevens, J; Birkhoff, W; Kamerling, Imc; Danhof, M; Meijer, J H; Burggraaf, J

2016-01-01

Understanding the factors influencing a drug's potential to prolong the QTc interval on an electrocardiogram is essential for the correct evaluation of its safety profile. To explore the effect of dosing time on drug-induced QTc prolongation, a randomized, crossover, clinical trial was conducted in

Presence or Absence of QTc Prolongation in Buprenorphine-Naloxone Among Youth With Opioid Dependence.

Science.gov (United States)

Poole, Sabrina A; Pecoraro, Anna; Subramaniam, Geetha; Woody, George; Vetter, Victoria L

2016-01-01

The aim of the study was to evaluate buprenorphine-naloxone effects on the QTc in youth with opioid dependence. Buprenorphine is a partial agonist that is an effective treatment for opioid dependence. Compared with methadone, it has a lower risk of QTc prolongation in adults, but is less studied in the youth. It may also reduce the risk of torsades de pointes (TdP)--an uncommon variant of polymorphic ventricular tachycardia--that can result in syncope, ventricular fibrillation, and sudden death. Secondary analysis of the electrocardiogram data from 95 individuals who participated in a multisite trial for youth with opioid dependence. The participants were randomized to a 2-week (DETOX) or a 12-week course of buprenorphine-naloxone (BUP). At baseline, 12-lead electrocardiograms were done at weeks 4 and 12, and QTc intervals were hand-measured and calculated using Bazett formula. Increases above 60 milliseconds were considered clinically significant, and readings above 450 milliseconds (in men) and 470 milliseconds (in women) indicated a prolonged QTc. Mean QTc intervals were higher for BUP than for DETOX participants at baseline, week 4, and week 12 (P = 0.045), and women had longer mean QTc intervals than men (P DETOX patients. Minimal changes in the QTc were seen at 4 and 12 weeks in a few patients in both groups. There was no evidence that buprenorphine-naloxone alone increased the QTc to a level that increased the risk for TdP.

Effects of a screening and treatment protocol with haloperidol on post-cardiotomy delirium

DEFF Research Database (Denmark)

Schrøder Pedersen, Sofie; Kirkegaard, Thomas; Balslev Jørgensen, Martin

2014-01-01

OBJECTIVES: Post-cardiotomy delirium is common and associated with increased morbidity and mortality. No gold standard exists for detecting delirium, and evidence to support the choice of treatment is needed. Haloperidol is widely used for treating delirium, but indication, doses and therapeutic...... targets vary. Moreover, doubt has been raised regarding overall efficacy. The purpose of this study was to assess the effect of a combination of early detection and standardized treatment with haloperidol on post-cardiotomy delirium, with the hypothesis that the proportion of delirium- and coma-free days...... could be increased. Length of stay (LOS), complications and 180-day mortality are reported. METHODS: Prospective interventional cohort study. One hundred and seventeen adult patients undergoing cardiac surgery were included before introduction of a screening and treatment protocol with haloperidol...

Marked QTc prolongation and Torsades de Pointes in patients with chronic inflammatory arthritis

Directory of Open Access Journals (Sweden)

Pietro Enea Lazzerini

2016-09-01

Full Text Available Mounting evidence indicates that in chronic inflammatory arthritis (CIA, QTc prolongation is frequent and correlates with systemic inflammatory activation. Notably, basic studies demonstrated that inflammatory cytokines induce profound changes in potassium and calcium channels resulting in a prolonging effect on cardiomyocyte action potential duration (APD, thus on the QT interval on the electrocardiogram. Moreover, it has been demonstrated that in RA patients the risk of SCD is significantly increased when compared to non-RA subjects. Conversely, to date no data are available about Torsades de Pointes (TdP prevalence in CIA, and the few case reported considered CIA only an incidental concomitant disease, not contributing factor to TdP development.We report three patients with active CIA developing marked QTc prolongation, in two cases complicated with TdP degenerating to cardiac arrest. In these patients, a blood sample was obtained within 24h from TdP/marked QTc prolongation occurrence and levels of IL-6, TNF-alpha and IL-1 were evaluated. In all three cases, IL-6 was markedly elevated, ~10 to 100 times more than reference values. Moreover, one patient also showed high circulating levels of TNF-alpha and IL-1. In conclusion, active CIA may represent a currently overlooked QT-prolonging risk factor, potentially contributing in the presence of other classical risk factors to TdP occurrence. In particular, a relevant role may be played by elevated circulating IL-6 levels via direct electrophysiological effects on the heart. This observation should be carefully kept in mind, particularly when recognizable risk factors are already present and/or the addition of QT-prolonging drugs is required.

Randomized Controlled Double-blind Trial Comparing Haloperidol Combined With Conventional Therapy to Conventional Therapy Alone in Patients With Symptomatic Gastroparesis.

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Roldan, Carlos J; Chambers, Kimberly A; Paniagua, Linda; Patel, Sonali; Cardenas-Turanzas, Marylou; Chathampally, Yashwant

2017-11-01

Gastroparesis is a debilitating condition that causes nausea, vomiting, and abdominal pain. Management includes analgesics and antiemetics, but symptoms are often refractory. Haloperidol has been utilized in the palliative care setting for similar symptoms. The study objective was to determine whether haloperidol as an adjunct to conventional therapy would improve symptoms in gastroparesis patients presenting to the emergency department (ED). This was a randomized, double-blind, placebo-controlled trial of adult ED patients with acute exacerbation of previously diagnosed gastroparesis. The treatment group received 5 mg of haloperidol plus conventional therapy (determined by the treating physician). The control group received a placebo plus conventional therapy. The severity of each subject's abdominal pain and nausea were assessed before intervention and every 15 minutes thereafter for 1 hour using a 10-point scale for pain and a 5-point scale for nausea. Primary outcomes were decreased pain and nausea 1 hour after treatment. Of the 33 study patients, 15 were randomized to receive haloperidol. Before treatment, the mean intensity of pain was 8.5 in the haloperidol group and 8.28 in the placebo group; mean pretreatment nausea scores were 4.53 and 4.11, respectively. One hour after therapy, the mean pain and nausea scores in the haloperidol group were 3.13 and 1.83 compared to 7.17 and 3.39 in the placebo group. The reduction in mean pain intensity therapy was 5.37 in the haloperidol group (p ≤ 0.001) compared to 1.11 in the placebo group (p = 0.11). The reduction in mean nausea score was 2.70 in the haloperidol group (p ≤ 0.001) and 0.72 in the placebo group (p = 0.05). Therefore, the reductions in symptom scores were statistically significant in the haloperidol group but not in the placebo group. No adverse events were reported. Haloperidol as an adjunctive therapy is superior to placebo for acute gastroparesis symptoms. © 2017 by the Society for Academic

Effectiveness of haloperidol prophylaxis in critically ill patients with a high risk of delirium: a systematic review.

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Santos, Eduardo; Cardoso, Daniela; Neves, Hugo; Cunha, Madalena; Rodrigues, Manuel; Apóstolo, João

2017-05-01

Delirium is associated with increased intensive care unit and hospital length of stay, prolonged duration of mechanical ventilation, unplanned removal of tubes and catheters, and increased morbidity and mortality. Prophylactic treatment with low-dose haloperidol may have beneficial effects for critically ill patients with a high risk of delirium. To identify the effectiveness of haloperidol prophylaxis in critically ill patients with a high risk for delirium. Patients with a predicted high risk of delirium, aged 18 years or over, and in intensive care units. Patients with a history of concurrent antipsychotic medication use were excluded. Haloperidol prophylaxis for preventing delirium. Experimental and epidemiological study designs. Primary outcome is the incidence of delirium. Secondary outcomes are duration of mechanical ventilation, incidence of re-intubation, incidence of unplanned/accidental removal of tubes/lines and catheters, intensive care unit and hospital length of stay, and re-admissions to both settings. An initial search of MEDLINE and CINAHL was undertaken, followed by a second search for published and unpublished studies from January 1967 to September 2015 in major healthcare-related electronic databases. Studies in English, Spanish and Portuguese were included. Two independent reviewers assessed the methodological quality of five studies using the standardized critical appraisal instrument from the Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument. There was general agreement among the reviewers to exclude one relevant study due to methodological quality. Data were extracted using the JBI data extraction form for experimental studies and included details about the interventions, populations, study methods and outcomes of significance to the review questions. Significant differences were found between participants, interventions, outcome measures (clinical heterogeneity) and designs (methodological heterogeneity

Haloperidol Disrupts Opioid-Antinociceptive Tolerance and Physical Dependence

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Yang, Cheng; Chen, Yan; Tang, Lei

2011-01-01

Previous studies from our laboratory and others have implicated a critical role of Ca2+/calmodulin-dependent protein kinase II (CaMKII) in opioid tolerance and dependence. Translational research targeting the CaMKII pathway is challenging, if not impossible, because of a lack of selective inhibitors. We discovered in a preliminary study that haloperidol, a butyrophenone antipsychotic drug, inhibited CaMKII, which led us to hypothesize that haloperidol can attenuate opioid tolerance and dependence by inhibiting CaMKII. The hypothesis was tested in two rodent models of opioid tolerance and dependence. Pretreatment with haloperidol (0.2–1.0 mg/kg i.p.) prevented the development of morphine tolerance and dependence in a dose-dependent manner. Short-term treatment with haloperidol (0.06–0.60 mg/kg i.p.) dose-dependently reversed the established morphine-antinociceptive tolerance and physical dependence. Correlating with behavioral effects, pretreatment or short-term treatment with haloperidol dose-dependently inhibited morphine-induced up-regulation of supraspinal and spinal CaMKIIα activity. Moreover, haloperidol given orally was also effective in attenuating morphine-induced CaMKIIα activity, antinociceptive tolerance, and physical dependence. Taken together, these data suggest that haloperidol attenuates opioid tolerance and dependence by suppressing CaMKII activity. Because haloperidol is a clinically used drug that can be taken orally, we propose that the drug may be of use in attenuating opioid tolerance and dependence. PMID:21436292

Haloperidol plus promethazine for psychosis-induced aggression.

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Huf, Gisele; Alexander, Jacob; Gandhi, Pinky; Allen, Michael H

2016-11-25

Health services often manage agitated or violent people, and such behaviour is particularly prevalent in emergency psychiatric services (10%). The drugs used in such situations should ensure that the person becomes calm swiftly and safely. To examine whether haloperidol plus promethazine is an effective treatment for psychosis-induced aggression. On 6 May 2015 we searched the Cochrane Schizophrenia Group's Register of Trials, which is compiled by systematic searches of major resources (including MEDLINE, EMBASE, AMED, BIOSIS, CINAHL, PsycINFO, PubMed, and registries of clinical trials) and their monthly updates, handsearches, grey literature, and conference proceedings. All randomised clinical trials with useable data focusing on haloperidol plus promethazine for psychosis-induced aggression. We independently extracted data. For binary outcomes, we calculated risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat basis. For continuous data, we estimated the mean difference (MD) between groups and its 95% CI. We employed a fixed-effect model for analyses. We assessed risk of bias for included studies and created 'Summary of findings' tables using GRADE. We found two new randomised controlled trials (RCTs) from the 2015 update searching. The review now includes six studies, randomising 1367 participants and presenting data relevant to six comparisons.When haloperidol plus promethazine was compared with haloperidol alone for psychosis-induced aggression for the outcome not tranquil or asleep at 30 minutes, the combination treatment was clearly more effective (n=316, 1 RCT, RR 0.65, 95% CI 0.49 to 0.87, high-quality evidence). There were 10 occurrences of acute dystonia in the haloperidol alone arm and none in the combination group. The trial was stopped early as haloperidol alone was considered to be too toxic.When haloperidol plus promethazine was compared with olanzapine, high-quality data showed both approaches to be tranquillising. It was

Tranquilização rápida para pacientes agitados nos serviços de emergência psiquiátrica: um ensaio clínico randomisado de olanzapina, ziprasidona, haloperidol mais prometazina, haloperidol mais midazolam e haloperidol em monoterapia

OpenAIRE

Baldaçara, Leonardo; Sanches, Marsal; Cordeiro, Daniel Cruz; Jackowski, Andrea Parolin

2011-01-01

OBJECTIVE: To compare the effectiveness of intramuscular olanzapine, ziprasidone, haloperidol plus promethazine, haloperidol plus midazolam and haloperidol alone as the first medication(s) used to treat patients with agitation and aggressive behavior. METHOD: One hundred fifty patients with agitation caused by psychotic or bipolar disorder were randomly assigned under double-blind conditions to receive olanzapine, ziprasidone, haloperidol plus midazolam, haloperidol plus promethazine or halop...

Effects of haloperidol on Kv4.3 potassium channels.

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Lee, Hong Joon; Sung, Ki-Wug; Hahn, Sang June

2014-10-05

Haloperidol is commonly used in clinical practice to treat acute and chronic psychosis, but it also has been associated with adverse cardiovascular events. We investigated the effects of haloperidol on Kv4.3 currents stably expressed in CHO cells using a whole-cell patch-clamp technique. Haloperidol did not significantly inhibit the peak amplitude of Kv4.3, but accelerated the decay rate of inactivation of Kv4.3 in a concentration-dependent manner. Thus, the effects of haloperidol on Kv4.3 were estimated from the integral of the Kv4.3 currents during the depolarization pulse. The Kv4.3 was decreased by haloperidol in a concentration-dependent manner with an IC50 value of 3.6 μM. Haloperidol accelerated the decay rate of Kv4.3 inactivation and activation kinetics in a concentration-dependent manner, thereby decreasing the time-to-peak. Haloperidol shifted the voltage dependence of the steady-state activation and inactivation of Kv4.3 in a hyperpolarizing direction. Haloperidol also caused an acceleration of the closed-state inactivation of Kv4.3. Haloperidol produced a use-dependent block of Kv4.3, which was accompanied by a slowing of recovery from the inactivation of Kv4.3. These results suggest that haloperidol blocks Kv4.3 by both interacting with the open state of Kv4.3 channels during depolarization and accelerating the closed-state inactivation at subthreshold membrane potentials. Copyright © 2014 Elsevier B.V. All rights reserved.

The Presence or Absence of QTc Prolongation in Buprenorphine-Naloxone Among Youth with Opioid Dependence

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Poole, Sabrina A.; Pecoraro, Anna; Subramaniam, Geetha; Woody, George; Vetter, Victoria L

2015-01-01

Objective To evaluate buprenorphine-naloxone effects on the QTc in youth with opioid dependence. Buprenorphine is a partial agonist that is an effective treatment for opioid dependence. Compared to methadone it has a lower risk of QTc prolongation in adults but is less well studied in youth. It may also reduce the risk for torsades de pointes (TdP) an uncommon variant of polymorphic ventricular tachycardia, that can result in syncope, ventricular fibrillation, and sudden death. Methods Secondary analysis of ECG data from 95 subjects who participated in a multi-site trial for youth with opioid dependence. Subjects were randomized to a 2-week (DETOX), or a 12-week course of buprenorphine-naloxone (BUP). 12-lead ECGs were done at baseline, weeks 4 and 12, and QTc intervals were hand measured and calculated using Bazett's formula. Increases > 60 milliseconds (ms) were considered clinically significant, and readings > 450 ms (males) and 470 ms (females) indicated a prolonged QTc. Results Mean QTc intervals were higher for BUP than DETOX participants at baseline, week 4, and week 12 (p = 0.045), and females had longer mean QTc intervals than males (p DETOX patients. Minimal changes in the QTc were seen at 4 and 12-weeks in a few patients in both groups. There was no evidence that buprenorphine-naloxone alone increased the QTc to a level that increased the risk for TdP. PMID:26690291

Levo-α-acetylmethadol (LAAM induced QTc-prolongation - results from a controlled clinical trial

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Wieneke H

2009-01-01

Full Text Available Abstract Background Due to potential proarrhythmic side-effects levo-α-Acetylmethadol (LAAM is currently not available in EU countries as maintenance drug in the treatment of opiate addiction. However, recent studies and meta-analyses underline the clinical advantages of LAAM with respect to the reduction of heroin use. Thus a reappraisal of LAAM has been demanded. The aim of the present study was to evaluate the relative impact of LAAM on QTc-interval, as a measure of pro-arrhythmic risk, in comparison to methadone, the current standard in substitution therapy. Methods ECG recordings were analysed within a randomized, controlled clinical trial evaluating the efficacy and tolerability of maintenance treatment with LAAM compared with racemic methadone. Recordings were done at two points: 1 during a run-in period with all patients on methadone and 2 24 weeks after randomisation into methadone or LAAM treatment group. These ECG recordings were analysed with respect to QTc-values and QTc-dispersion. Mean values as well as individual changes compared to baseline parameters were evaluated. QTc-intervals were classified according to CPMP-guidelines. Results Complete ECG data sets could be obtained in 53 patients (31 LAAM-group, 22 methadone-group. No clinical cardiac complications were observed in either group. After 24 weeks, patients receiving LAAM showed a significant increase in QTc-interval (0.409 s ± 0.022 s versus 0.418 s ± 0.028 s, p = 0.046, whereas no significant changes could be observed in patients remaining on methadone. There was no statistically significant change in QTc-dispersion in either group. More patients with borderline prolonged and prolonged QTc-intervals were observed in the LAAM than in the methadone treatment group (n = 7 vs. n = 1; p = 0.1. Conclusions In this controlled trial LAAM induced QTc-prolongation in a higher degree than methadone. Given reports of severe arrhythmic events, careful ECG-monitoring is recommended

Piracetam reverses haloperidol-induced catalepsy in mice

OpenAIRE

SALAM, Omar Abdel; NADA, Somaia

2014-01-01

To investigate the memory-enhancing drugs piracetam, vinpocetine, and ginkgo biloba for their ability to reduce catalepsy in mice treated with haloperidol. Haloperidol is a classic neuroleptic drug that induces motor abnormalities and cognitive impairment due to a blockade of dopamine D2 receptors in the striatum. Materials and methods: Catalepsy was induced by intraperitoneal haloperidol (2 mg/kg) administration. The drugs being tested were either administered intraperitoneally (IP) along ...

Haloperidol Injection

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... haloperidol extended-release injection are used to treat schizophrenia (a mental illness that causes disturbed or unusual ... may help control your symptoms but will not cure your condition. Continue to keep appointments to receive ...

QTc interval prolongation in children with Turner syndrome: the results of exercise testing and 24-h ECG.

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Dalla Pozza, Robert; Bechtold, Susanne; Urschel, Simon; Netz, Heinrich; Schwarz, Hans-Peter

2009-01-01

Turner syndrome (TS) is the most common sex chromosome abnormality in females. Recently, a prolongation of the rate-corrected QT (QTc) interval in the electrocardiogram (ECG) of TS patients has been reported. A prolonged QTc interval has been correlated to an increased risk for sudden cardiac death, and medical treatment is warranted in patients with congenital long QT syndrome (LQTS). Additionally, several drugs of common use are contraindicated in LQTS because of their effects on myocardial repolarization. The importance of the QTc prolongation in TS patients is not known at present. Eighteen TS patients with a prolonged QTc interval (group 1) and 11 TS patients with a normal QTc interval (group 2) (mean age 12.6+/-3.1 vs. 11.8+/-2.1 years, respectively) were tested. The QTc interval was calculated during exercise testing and during 24-h ECG recordings. None of the patients experienced adverse cardiac events during the tests. The mean QTc interval decreased from 0.467 to 0.432 s in group 1 and from 0.432 to 0.412 s in group 2. During the 24-h ECG, the maximum QTc interval was significantly prolonged in group 1 (0.51 vs. 0.465 s, pinformation about the cardiac risk in the single TS patient with a prolonged QTc interval. This helps in counseling these girls, as clear therapeutic guidelines are currently lacking.

Prolonged QTc interval and risk of sudden cardiac death in a population of older adults

DEFF Research Database (Denmark)

Straus, Sabine M J M; Kors, Jan A; De Bruin, Marie L

2006-01-01

OBJECTIVES: This study sought to investigate whether prolongation of the heart rate-corrected QT (QTc) interval is a risk factor for sudden cardiac death in the general population. BACKGROUND: In developed countries, sudden cardiac death is a major cause of cardiovascular mortality. Prolongation...... of the QTc interval has been associated with ventricular arrhythmias, but in most population-based studies no consistent association was found between QTc prolongation and total or cardiovascular mortality. Only very few of these studies specifically addressed sudden cardiac death. METHODS: This study......). The association between a prolonged QTc interval and sudden cardiac death was estimated using Cox proportional hazards analysis. RESULTS: During an average follow-up period of 6.7 years (standard deviation, 2.3 years) 125 patients died of sudden cardiac death. An abnormally prolonged QTc interval (>450 ms in men...

Effect of Lorazepam With Haloperidol vs Haloperidol Alone on Agitated Delirium in Patients With Advanced Cancer Receiving Palliative Care: A Randomized Clinical Trial.

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Hui, David; Frisbee-Hume, Susan; Wilson, Annie; Dibaj, Seyedeh S; Nguyen, Thuc; De La Cruz, Maxine; Walker, Paul; Zhukovsky, Donna S; Delgado-Guay, Marvin; Vidal, Marieberta; Epner, Daniel; Reddy, Akhila; Tanco, Kimerson; Williams, Janet; Hall, Stacy; Liu, Diane; Hess, Kenneth; Amin, Sapna; Breitbart, William; Bruera, Eduardo

2017-09-19

The use of benzodiazepines to control agitation in delirium in the last days of life is controversial. To compare the effect of lorazepam vs placebo as an adjuvant to haloperidol for persistent agitation in patients with delirium in the setting of advanced cancer. Single-center, double-blind, parallel-group, randomized clinical trial conducted at an acute palliative care unit at MD Anderson Cancer Center, Texas, enrolling 93 patients with advanced cancer and agitated delirium despite scheduled haloperidol from February 11, 2014, to June 30, 2016, with data collection completed in October 2016. Lorazepam (3 mg) intravenously (n = 47) or placebo (n = 43) in addition to haloperidol (2 mg) intravenously upon the onset of an agitation episode. The primary outcome was change in Richmond Agitation-Sedation Scale (RASS) score (range, -5 [unarousable] to 4 [very agitated or combative]) from baseline to 8 hours after treatment administration. Secondary end points were rescue neuroleptic use, delirium recall, comfort (perceived by caregivers and nurses), communication capacity, delirium severity, adverse effects, discharge outcomes, and overall survival. Among 90 randomized patients (mean age, 62 years; women, 42 [47%]), 58 (64%) received the study medication and 52 (90%) completed the trial. Lorazepam + haloperidol resulted in a significantly greater reduction of RASS score at 8 hours (-4.1 points) than placebo + haloperidol (-2.3 points) (mean difference, -1.9 points [95% CI, -2.8 to -0.9]; P haloperidol group required less median rescue neuroleptics (2.0 mg) than the placebo + haloperidol group (4.0 mg) (median difference, -1.0 mg [95% CI, -2.0 to 0]; P = .009) and was perceived to be more comfortable by both blinded caregivers and nurses (caregivers: 84% for the lorazepam + haloperidol group vs 37% for the placebo + haloperidol group; mean difference, 47% [95% CI, 14% to 73%], P = .007; nurses: 77% for the lorazepam + haloperidol

Haloperidol, a Novel Treatment for Cannabinoid Hyperemesis Syndrome.

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Witsil, Joanne C; Mycyk, Mark B

Cannabinoid hyperemesis syndrome (CHS) is typically unresponsive to conventional pharmacologic antiemetics, and patients often require excessive laboratory and radiographic testing and hospital admission. We report 4 cases of CHS that failed standard emergency department therapy but improved significantly after treatment with haloperidol. Although the exact mechanism for CHS remains unclear, dysregulation at cannabinoid type 1 seems to play a role. Recent animal data demonstrate complex interactions between dopamine and cannabinoid type 1 signaling, a potential mechanism for haloperidol success in patients with CHS. Our success with haloperidol in these 4 patients warrants further investigation of haloperidol as an emergency department treatment for CHS.

QTc interval length and QT dispersion as predictors of mortality in patients with non-insulin-dependent diabetes

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Christensen, P K; Gall, M A; Major-Pedersen, A

2000-01-01

Patients with non-insulin-dependent diabetes (NIDDM) are at independent risk of cardiovascular death. The reason is only partially understood. The aim of our study was therefore to evaluate the impact of corrected QT interval length (QTc) and QT dispersion (QT-disp) on mortality in a cohort of 32....... Our study showed a high prevalence of QTc and QT-disp abnormalities and indicated that QTc-max but not QT-disp is an independent predictor of all cause and cardiovascular mortality in NIDDM patients.......-seven percent of the patients with PQTc died compared with 17% with normal QTc interval (pcause mortality; QTc-max (p....01), retinopathy (pcreatinine (p

Prognostic implications of mutation-specific QTc standard deviation in congenital long QT syndrome

NARCIS (Netherlands)

Mathias, Andrew; Moss, Arthur J.; Lopes, Coeli M.; Barsheshet, Alon; McNitt, Scott; Zareba, Wojciech; Robinson, Jennifer L.; Locati, Emanuela H.; Ackerman, Michael J.; Benhorin, Jesaia; Kaufman, Elizabeth S.; Platonov, Pyotr G.; Qi, Ming; Shimizu, Wataru; Towbin, Jeffrey A.; Michael Vincent, G.; Wilde, Arthur A. M.; Zhang, Li; Goldenberg, Ilan

2013-01-01

Individual corrected QT interval (QTc) may vary widely among carriers of the same long QT syndrome (LQTS) mutation. Currently, neither the mechanism nor the implications of this variable penetrance are well understood. To hypothesize that the assessment of QTc variance in patients with congenital

Haloperidol aggravates transverse aortic constriction-induced heart failure via mitochondrial dysfunction.

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Shinoda, Yasuharu; Tagashira, Hideaki; Bhuiyan, Md Shenuarin; Hasegawa, Hideyuki; Kanai, Hiroshi; Fukunaga, Kohji

2016-07-01

Haloperidol is an antipsychotic drug that inhibits the dopamine D2 receptor among others. Haloperidol also binds the sigma-1 receptor (σ1R) and inhibits it irreversibly. A serious outcome of haloperidol treatment of schizophrenia patients is death due to sudden cardiac failure. Although the cause remains unclear, we hypothesized that these effects were mediated by chronic haloperidol inhibition of cardiac σ1R. To test this, we treated neonatal rat cardiomyocytes with haloperidol, exposed them to angiotensin II and assessed hypertrophy, σ1R expression, mitochondrial Ca(2+) transport and ATP levels. In this context, haloperidol treatment altered mitochondrial Ca(2+) transport resulting in decreased ATP content by inactivating cardiac σ1R and/or reducing its expression. We also performed transverse aortic constriction (TAC) and then treated mice with haloperidol. After two weeks, haloperidol-treated mice showed enhanced heart failure marked by deteriorated cardiac function, reduced ATP production and increasing mortality relative to TAC only mice. ATP supplementation via sodium pyruvate rescued phenotypes seen in haloperidol-treated TAC mice. We conclude that σ1R inactivation or downregulation in response to haloperidol treatment impairs mitochondrial Ca(2+) mobilization, depleting ATP depletion from cardiomyocytes. These findings suggest a novel approach to mitigate haloperidol-related adverse effects in schizophrenia patients by ATP supplementation. Copyright © 2016 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Haloperidol aggravates transverse aortic constriction-induced heart failure via mitochondrial dysfunction

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Yasuharu Shinoda

2016-07-01

Full Text Available Haloperidol is an antipsychotic drug that inhibits the dopamine D2 receptor among others. Haloperidol also binds the sigma-1 receptor (σ1R and inhibits it irreversibly. A serious outcome of haloperidol treatment of schizophrenia patients is death due to sudden cardiac failure. Although the cause remains unclear, we hypothesized that these effects were mediated by chronic haloperidol inhibition of cardiac σ1R. To test this, we treated neonatal rat cardiomyocytes with haloperidol, exposed them to angiotensin II and assessed hypertrophy, σ1R expression, mitochondrial Ca2+ transport and ATP levels. In this context, haloperidol treatment altered mitochondrial Ca2+ transport resulting in decreased ATP content by inactivating cardiac σ1R and/or reducing its expression. We also performed transverse aortic constriction (TAC and then treated mice with haloperidol. After two weeks, haloperidol-treated mice showed enhanced heart failure marked by deteriorated cardiac function, reduced ATP production and increasing mortality relative to TAC only mice. ATP supplementation via sodium pyruvate rescued phenotypes seen in haloperidol-treated TAC mice. We conclude that σ1R inactivation or downregulation in response to haloperidol treatment impairs mitochondrial Ca2+ mobilization, depleting ATP depletion from cardiomyocytes. These findings suggest a novel approach to mitigate haloperidol-related adverse effects in schizophrenia patients by ATP supplementation.

Effects of anthracycline, cyclophosphamide and taxane chemotherapy on QTc measurements in patients with breast cancer.

Science.gov (United States)

Veronese, Pedro; Hachul, Denise Tessariol; Scanavacca, Mauricio Ibrahim; Hajjar, Ludhmila Abrahão; Wu, Tan Chen; Sacilotto, Luciana; Veronese, Carolina; Darrieux, Francisco Carlos da Costa

2018-01-01

Acute and subacute cardiotoxicity are characterized by prolongation of the corrected QT interval (QTc) and other measures derived from the QTc interval, such as QTc dispersion (QTdc) and transmural dispersion of repolarization (DTpTe). Although anthracyclines prolong the QTc interval, it is unclear whether breast cancer patients who undergo the ACT chemotherapy regimen of anthracycline (doxorubicin: A), cyclophosphamide (C) and taxane (T) may present with QTc, QTdc and DTpTe prolongation. Twenty-three consecutive patients with breast cancer were followed prospectively during ACT chemotherapy and were analyzed according to their QT measurements. QTc, QTdc and DTpTe measurements were determined by a 12-lead electrocardiogram (EKG) prior to chemotherapy (baseline), immediately after the first phase of anthracycline and cyclophosphamide (AC) treatment, and immediately after T treatment. Serum troponin and B-type natriuretic peptide (BNP) levels were also measured. Compared to baseline values, the QTc interval was significantly prolonged after the AC phase (439.7 ± 33.2 ms vs. 472.5 ± 36.3 ms, p = 0.001) and after T treatment (439.7 ± 33.2 ms vs. 467.9 ± 42.6 ms, p < 0.001). Troponin levels were elevated after the AC phase (23.0 pg/mL [min-max: 6.0-85.0] vs. 6.0 pg/mL [min-max: 6.0-22.0], p < 0.001) and after T treatment (25.0 pg/mL [min-max: 6.0-80.0] vs. 6.0 pg/mL [min-max: 6.0-22.0], p < 0.001) compared to baseline values. In this prospective study of patients with non-metastatic breast cancer who underwent ACT chemotherapy, significant QTc prolongation and an elevation in serum troponin levels were observed.

QTc interval in patients with schizophrenia receiving antipsychotic treatment as monotherapy or polypharmacy

DEFF Research Database (Denmark)

Elliott, Anja; Mørk, Thibault Johan; Højlund, Mikkel

2017-01-01

Objective: Antipsychotics are associated with a polymorphic ventricular tachycardia, torsades de pointes, which, in the worst case, can lead to sudden cardiac death. The QT interval corrected for heart rate (QTc) is used as a clinical proxy for torsades de pointes. The QTc interval can be prolonged...

Haloperidol aggravates transverse aortic constriction-induced heart failure via mitochondrial dysfunction

OpenAIRE

Yasuharu Shinoda; Hideaki Tagashira; Md. Shenuarin Bhuiyan; Hideyuki Hasegawa; Hiroshi Kanai; Kohji Fukunaga

2016-01-01

Haloperidol is an antipsychotic drug that inhibits the dopamine D2 receptor among others. Haloperidol also binds the sigma-1 receptor (σ1R) and inhibits it irreversibly. A serious outcome of haloperidol treatment of schizophrenia patients is death due to sudden cardiac failure. Although the cause remains unclear, we hypothesized that these effects were mediated by chronic haloperidol inhibition of cardiac σ1R. To test this, we treated neonatal rat cardiomyocytes with haloperidol, exposed them...

Commentary on: ?Levofloxacin?Induced QTc Prolongation Depends on the Time of Drug Administration?

OpenAIRE

Garnett, C; Johannesen, L

2016-01-01

Circadian variations in the corrected QT (QTc) interval have been documented in clinical trials. Animal models show circadian variations in expression of the cardiac ion channels that are necessary to maintain the heart's electrophysiological properties. Can these diurnal rhythms in QTc affect the ability of a drug to delay cardiac repolarization?

Haloperidol-induced changes in neuronal activity in the striatum of the freely moving rat

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Dorin eYael

2013-12-01

Full Text Available The striatum is the main input structure of the basal ganglia, integrating input from the cerebral cortex and the thalamus, which is modulated by midbrain dopaminergic input. Dopamine modulators, including agonists and antagonists, are widely used to relieve motor and psychiatric symptoms in a variety of pathological conditions. Haloperidol, a dopamine D2 antagonist, is commonly used in multiple psychiatric conditions and motor abnormalities. This article reports the effects of haloperidol on the activity of three major striatal subpopulations: medium spiny projection neurons (MSNs, fast spiking interneurons (FSIs and tonically active neurons (TANs. We implanted multi-wire electrode arrays in the rat dorsal striatum and recorded the activity of multiple single units in freely moving animals before and after systemic haloperidol injection. Haloperidol decreased the firing rate of FSIs and MSNs while increasing their tendency to fire in an oscillatory manner in the high voltage spindle (HVS frequency range of 7-9 Hz. Haloperidol led to an increased firing rate of TANs but did not affect their non-oscillatory firing pattern and their typical correlated firing activity. Our results suggest that dopamine plays a key role in tuning both single unit activity and the interactions within and between different subpopulations in the striatum in a differential manner. These findings highlight the heterogeneous striatal effects of tonic dopamine regulation via D2 receptors which potentially enable the treatment of diverse pathological states associated with basal ganglia dysfunction.

Levofloxacin?Induced QTc Prolongation Depends on the Time of Drug Administration

OpenAIRE

Kervezee, L; Gotta, V; Stevens, J; Birkhoff, W; Kamerling, IMC; Danhof, M; Meijer, JH; Burggraaf, J

2016-01-01

Understanding the factors influencing a drug's potential to prolong the QTc interval on an electrocardiogram is essential for the correct evaluation of its safety profile. To explore the effect of dosing time on drug-induced QTc prolongation, a randomized, crossover, clinical trial was conducted in which 12 healthy male subjects received levofloxacin at 02:00, 06:00, 10:00, 14:00, 18:00, and 22:00. Using a pharmacokinetic-pharmacodynamic (PK-PD) modeling approach to account for variations in ...

RELATIONSHIP OF SLEEP DURATION AND QT INTERVAL IN OBESE AND NON-OBESE MEDICAL STUDENTS

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Hariprasad

2016-02-01

Full Text Available BACKGROUND Sleep deprivation has become a major concern in the modern era. It is found to have an inverse relation with obesity increasing cardiovascular diseases. This study was done to correlate effects of sleep deprivation & obesity with QT interval. OBJECTIVES 1. To assess sleep deprivation in medical students. 2. To measure QT interval and QTc in obese and normal weight medical students. 3. To correlate these QT interval and QTc values with sleep deprivation and obesity. METHODOLOGY In this cross sectional study by simple random sampling 30 obese and 30 normal weight individuals were selected based on Quetelet Index. They were further sub- grouped into Group A with 2-4 hrs., Group B with 4-6 hrs. and Group C with 6-8 hrs. of sleep duration, respectively. Electrocardiography was recorded and QT & QTc was measured. The mean and standard deviations were calculated and by 2 tailed t-test for equality of means, significance was established. RESULTS The QT interval measured in Group A has a mean 363±25.1 in normal weight whereas 374±31.6 in obese which is increased. In all groups QTc interval was within normal limits though more in obese individuals. But in group A obese 431±31.6 which shows borderline QTc prolongation (≥430-451ms in men. Thus severe sleep deprivation contributes to obesity and prolongs QTc interval to pathologically. CONCLUSIONS Our study concludes that sleep deprivation has significant correlation with QTc interval. Mild to moderate sleep deprivation affects obese more than normal weight & Severe sleep deprivation with obesity may lead to borderline QTc prolongation.

Cannabidiol attenuates haloperidol-induced catalepsy and c-Fos protein expression in the dorsolateral striatum via 5-HT1A receptors in mice.

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Sonego, Andreza B; Gomes, Felipe V; Del Bel, Elaine A; Guimaraes, Francisco S

2016-08-01

Cannabidiol (CBD) is a major non-psychoactive compound from Cannabis sativa plant. Given that CBD reduces psychotic symptoms without inducing extrapyramidal motor side-effects in animal models and schizophrenia patients, it has been proposed to act as an atypical antipsychotic. In addition, CBD reduced catalepsy induced by drugs with distinct pharmacological mechanisms, including the typical antipsychotic haloperidol. To further investigate this latter effect, we tested whether CBD (15-60mg/kg) would attenuate the catalepsy and c-Fos protein expression in the dorsal striatum induced by haloperidol (0.6mg/kg). We also evaluated if these effects occur through the facilitation of 5-HT1A receptor-mediated neurotransmission. For this, male Swiss mice were treated with CBD and haloperidol systemically and then subjected to the catalepsy test. Independent groups of animals were also treated with the 5-HT1A receptor antagonist WAY100635 (0.1mg/kg). As expected, haloperidol induced catalepsy throughout the experiments, an effect that was prevented by systemic CBD treatment 30min before haloperidol administration. Also, CBD, administered 2.5h after haloperidol, reversed haloperidol-induced catalepsy. Haloperidol also increased c-Fos protein expression in the dorsolateral striatum, an effect attenuated by previous CBD administration. CBD effects on catalepsy and c-Fos protein expression induced by haloperidol were blocked by the 5-HT1A receptor antagonist. We also evaluated the effects of CBD (60nmol) injection into the dorsal striatum on haloperidol-induced catalepsy. Similar to systemic administration, this treatment reduced catalepsy induced by haloperidol. Altogether, these results suggest that CBD acts in the dorsal striatum to improve haloperidol-induced catalepsy via postsynaptic 5-HT1A receptors. Copyright © 2016 Elsevier B.V. All rights reserved.

Risk prediction of cardiovascular death based on the QTc interval

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Nielsen, Jonas B; Graff, Claus; Rasmussen, Peter V

2014-01-01

electrocardiograms from 173 529 primary care patients aged 50-90 years were collected during 2001-11. The Framingham formula was used for heart rate-correction of the QT interval. Data on medication, comorbidity, and outcomes were retrieved from administrative registries. During a median follow-up period of 6......AIMS: Using a large, contemporary primary care population we aimed to provide absolute long-term risks of cardiovascular death (CVD) based on the QTc interval and to test whether the QTc interval is of value in risk prediction of CVD on an individual level. METHODS AND RESULTS: Digital...

Effect of Haloperidol on Survival Among Critically Ill Adults With a High Risk of Delirium: The REDUCE Randomized Clinical Trial.

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van den Boogaard, Mark; Slooter, Arjen J C; Brüggemann, Roger J M; Schoonhoven, Lisette; Beishuizen, Albertus; Vermeijden, J Wytze; Pretorius, Danie; de Koning, Jan; Simons, Koen S; Dennesen, Paul J W; Van der Voort, Peter H J; Houterman, Saskia; van der Hoeven, J G; Pickkers, Peter; van der Woude, Margaretha C. E.; Besselink, Anna; Hofstra, Lieuwe S; Spronk, Peter E; van den Bergh, Walter; Donker, Dirk W; Fuchs, Malaika; Karakus, Attila; Koeman, M; van Duijnhoven, Mirella; Hannink, Gerjon

2018-02-20

Results of studies on use of prophylactic haloperidol in critically ill adults are inconclusive, especially in patients at high risk of delirium. To determine whether prophylactic use of haloperidol improves survival among critically ill adults at high risk of delirium, which was defined as an anticipated intensive care unit (ICU) stay of at least 2 days. Randomized, double-blind, placebo-controlled investigator-driven study involving 1789 critically ill adults treated at 21 ICUs, at which nonpharmacological interventions for delirium prevention are routinely used in the Netherlands. Patients without delirium whose expected ICU stay was at least a day were included. Recruitment was from July 2013 to December 2016 and follow-up was conducted at 90 days with the final follow-up on March 1, 2017. Patients received prophylactic treatment 3 times daily intravenously either 1 mg (n = 350) or 2 mg (n = 732) of haloperidol or placebo (n = 707), consisting of 0.9% sodium chloride. The primary outcome was the number of days that patients survived in 28 days. There were 15 secondary outcomes, including delirium incidence, 28-day delirium-free and coma-free days, duration of mechanical ventilation, and ICU and hospital length of stay. All 1789 randomized patients (mean, age 66.6 years [SD, 12.6]; 1099 men [61.4%]) completed the study. The 1-mg haloperidol group was prematurely stopped because of futility. There was no difference in the median days patients survived in 28 days, 28 days in the 2-mg haloperidol group vs 28 days in the placebo group, for a difference of 0 days (95% CI, 0-0; P = .93) and a hazard ratio of 1.003 (95% CI, 0.78-1.30, P=.82). All of the 15 secondary outcomes were not statistically different. These included delirium incidence (mean difference, 1.5%, 95% CI, -3.6% to 6.7%), delirium-free and coma-free days (mean difference, 0 days, 95% CI, 0-0 days), and duration of mechanical ventilation, ICU, and hospital length of stay (mean difference

Beneficial effects of lycopene against haloperidol induced orofacial dyskinesia in rats: Possible neurotransmitters and neuroinflammation modulation.

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Datta, Swati; Jamwal, Sumit; Deshmukh, Rahul; Kumar, Puneet

2016-01-15

Tardive Dyskinesia is a severe side effect of chronic neuroleptic treatment consisting of abnormal involuntary movements, characterized by orofacial dyskinesia. The study was designed to investigate the protective effect of lycopene against haloperidol induced orofacial dyskinesia possibly by neurochemical and neuroinflammatory modulation in rats. Rats were administered with haloperidol (1mg/kg, i.p for 21 days) to induce orofacial dyskinesia. Lycopene (5 and 10mg/kg, p.o) was given daily 1hour before haloperidol treatment for 21 days. Behavioral observations (vacuous chewing movements, tongue protrusions, facial jerking, rotarod activity, grip strength, narrow beam walking) were assessed on 0th, 7th(,) 14th(,) 21st day after haloperidol treatment. On 22nd day, animals were killed and striatum was excised for estimation of biochemical parameters (malondialdehyde, nitrite and endogenous enzyme (GSH), pro-inflammatory cytokines [Tumor necrosis factor, Interleukin 1β, Interleukin 6] and neurotransmitters level (dopamine, serotonin, nor epinephrine, 5-Hydroxyindole acetic acid (5-HIAA), Homovanillic acid, 3,4- dihydroxyphenylacetic acid. Haloperidol treatment for 21 days impaired muscle co-ordination, motor activity and grip strength with an increased in orofacial dyskinetic movements. Further free radical generation increases MDA and nitrite levels, decreasing GSH levels in striatum. Neuroinflammatory markers were significantly increased with decrease in neurotransmitters levels. Lycopene (5 and 10mg/kg, p.o) treatment along with haloperidol significantly attenuated impairment in behavioral, biochemical, neurochemical and neuroinflammatory markers. Results of the present study attributed the therapeutic potential of lycopene in the treatment (prevented or delayed) of typical antipsychotic induced orofacial dyskinesia. Copyright © 2015 Elsevier B.V. All rights reserved.

[18F]haloperidol binding in baboon brain in vivo

International Nuclear Information System (INIS)

Yousef, Khalil A.; Fowler, Joanna S.; Volkow, Nora D.; Dewey, Stephen L.; Shea, Colleen; Schlyer, David J.; Gatley, S. John; Logan, Jean; Wolf, Alfred P.

1996-01-01

The binding of [ 18 F]haloperidol to dopamine D2 and to sigma recognition sites in baboon brain was examined using positron emission tomography (PET). Studies were performed at baseline and after treatment with either haloperidol (to evaluate saturability), (+)-butaclamol (which has specificity for dopamine D2 receptors) or (-)-butaclamol (which has specificity for sigma sites). Binding was widespread. Treatment with (-)-butaclamol had no effect, whereas (+)-butaclamol selectively reduced the uptake in striatum. Haloperidol increased the clearance rate from all brain regions. These results indicate that the binding profile of [ 18 F]haloperidol does not permit the selective examination of either dopamine D2 or sigma sites using PET

Haloperidol and Rimonabant Increase Delay Discounting in Rats Fed High-Fat and Standard-Chow Diets

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Boomhower, Steven R.; Rasmussen, Erin B.

2016-01-01

The dopamine and endocannabinoid neurotransmitter systems have been implicated in delay discounting, a measure of impulsive choice, and obesity. The current study was designed to determine the extent to which haloperidol and rimonabant affected delay discounting in rats fed standard-chow and high-fat diets. Sprague-Dawley rats were allowed to free-feed under a high-fat diet (4.73 kcal/g) or a standard-chow diet (3.0 kcal/g) for three months. Then, operant sessions began in which rats (n = 9 standard chow; n = 10 high-fat) chose between one sucrose pellet delivered immediately vs. three sucrose pellets after a series of delays. In another condition, carrot-flavored pellets replaced sucrose pellets. After behavior stabilized, acute injections of rimonabant (0.3-10 mg/kg) and haloperidol (0.003-0.1 mg/kg) were administered i.p. before some choice sessions in both pellet conditions. Haloperidol and rimonabant increased discounting in both groups of rats by decreasing percent choice for the larger reinforcer and area-under-the-curve (AUC) values. Rats in the high-fat diet condition demonstrated increased sensitivity to haloperidol compared to chow-fed controls: haloperidol increased discounting in both dietary groups in the sucrose condition,, but only in the high-fat-fed rats in the carrot-pellet condition. These findings indicate that blocking D2 and CB1 receptors results in increased delay discounting, and that a high-fat diet may alter sensitivity to dopaminergic compounds using the delay-discounting task. PMID:25000488

Classics in Chemical Neuroscience: Haloperidol.

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Tyler, Marshall W; Zaldivar-Diez, Josefa; Haggarty, Stephen J

2017-03-15

The discovery of haloperidol catalyzed a breakthrough in our understanding of the biochemical basis of schizophrenia, improved the treatment of psychosis, and facilitated deinstitutionalization. In doing so, it solidified the role for chemical neuroscience as a means to elucidate the molecular underpinnings of complex neuropsychiatric disorders. In this Review, we will cover aspects of haloperidol's synthesis, manufacturing, metabolism, pharmacology, approved and off-label indications, and adverse effects. We will also convey the fascinating history of this classic molecule and the influence that it has had on the evolution of neuropsychopharmacology and neuroscience.

Transcriptional dysregulation causes altered modulation of inhibition by haloperidol.

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Brady, Lillian J; Bartley, Aundrea F; Li, Qin; McMeekin, Laura J; Hablitz, John J; Cowell, Rita M; Dobrunz, Lynn E

2016-12-01

Many neuropsychiatric and neurodevelopmental disorders such as schizophrenia and autism involve interneuron transcriptional dysregulation. The transcriptional coactivator PGC-1α regulates gene expression in GABAergic interneurons, which are important for regulating hippocampal network activity. Genetic deletion of PGC-1α causes a decrease in parvalbumin expression, similar to what is observed in schizophrenia postmortem tissue. Our lab has previously shown that PGC-1α -/- mice have enhanced GABAergic inhibition onto CA1 pyramidal cells, which increases the inhibition/excitation (I/E) ratio, alters hippocampal circuit function, and impairs hippocampal dependent behavior. The typical antipsychotic haloperidol, a dopamine receptor antagonist with selectivity for D2-like receptors, has previously been shown to increase excitation in the CA1 region of hippocampus. We therefore tested whether haloperidol could normalize the I/E balance in CA1 of PGC-1α -/- mice, potentially improving circuit function and behavior. Surprisingly, we discovered instead that interneuron transcriptional dysregulation caused by loss of PGC-1α alters the effects of haloperidol on hippocampal synaptic transmission and circuit function. Acute administration of haloperidol causes disinhibition in CA1 and decreases the I/E ratio onto CA1 pyramidal cells in slices from PGC-1α +/+ mice, but not PGC-1α -/- mice. The spread of activity in CA1, assessed by voltage sensitive dye imaging, is increased by haloperidol in slices from PGC-1α +/+ mice; however haloperidol decreases the spread of activity in slices from PGC-1α -/- mice. Haloperidol increased the power of hippocampal gamma oscillation in slices from PGC-1α +/+ mice but reduced the power of gamma oscillations in slices from PGC-1α -/- mice. Nest construction, an innate hippocampal-dependent behavior, is inhibited by haloperidol in PGC-1α +/+ mice, but not in PGC-1α -/- mice, which already have impaired nest building. The effects of

Prophylactic Use of Haloperidol and Changes in Glucose Levels in Hospitalized Older Patients.

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van Keulen, Kris; Knol, Wilma; Schrijver, Edmée J M; van Marum, Rob J; van Strien, Astrid M; Nanayakkara, Prabath W B

2018-02-01

Treatment with antipsychotic drugs has been associated with glucose dysregulation in older outpatients, especially in the early stage of therapy. The underlying mechanism is, however, unclear. The aim of this study was to investigate changes in glucose levels during haloperidol use compared with the use of placebo among older hospitalized patients. This substudy was part of a larger multicenter, randomized, double blind, placebo-controlled clinical trial among hospitalized patients aged 70 years and older who had an increased risk of in-hospital delirium. Patients who were admitted to the Jeroen Bosch Hospital in 's-Hertogenbosch between June 2014 and February 2015 were invited to participate in the study. Participating patients were randomized for treatment and given 1 mg of haloperidol or a placebo twice daily for a maximum of 7 consecutive days (14 doses). Exclusion criteria for this substudy were the use of corticosteroids and changes in diabetes medication. Random blood samples to determine glucose levels were collected before day 1 and on day 6 of the study. Student independent sample t test was used to determine differences in glucose changes between both groups. Twenty-nine patients were included (haloperidol, n = 14; placebo, n = 15). The mean glucose level for placebo users was 139.3 mg/dL (SD, 50.1) on day 1 and 140.8 mg/dL (SD, 45.7) on day 6, and the mean glucose level for haloperidol users was 139.9 mg/dL (SD, 71.0) on day 1 and 150.2 mg/dL (SD, 39.1) on day 6. The difference was not statistically significant (P = 0.685). Short-term prophylactic use of haloperidol was not associated with changes in glucose levels in older hospitalized patients compared with those given a placebo in this small study.

A Randomized Open Label Comparison of the Effects ofRisperidone and Haloperidol on Sexual Function

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S. Jaber Mousavi

2009-12-01

Full Text Available "n Objective: "nSexual dysfunction in patients who take antipsychotics causes adecline in their quality of life and medication acceptance. Considering the restrictions in cross sectional design of many earlier researches, we used a clinical trial aimed at assessing sexual dysfunction by substituting Risperidone, an atypical antipsychotic drug, with Haloperidol, a typical one . "n "n "nMethod: This clinical trial was conducted on 51 patients who had been using Risperidone with a minimum dose of 2 mg/daily for at least 2 months. The patients were randomly divided into 2 groups. The first group continued taking Risperidone, whereas the second group was given Haloperidol. Sexual function prior to and after the drug substitution was assessed using a sexual questionnaire designed to assess four stages of sexual function . "nResults: Compared to those who changed their medication to Haloperidol, the patients who remained on Risperidone therapy suffered from more sexual dysfunction, especially in their tendency towards having sexual activities (P= 0.01, post menstrual sexual activity (P= 0.002, and reaching orgasm in their sexual activities (P= 0.04; however in the Haloperidol group, no significant difference was observed before and after the change in medication . "nConclusion: Although Risperidone and Haloperidol can both disturb patients'sexual function, the side effects of Risperidone are stronger. Hence toprevent the decline of medication acceptance or irregular consumption by patients which may lead to possible relapse, substitution of Risperidone withanother drug with fewer side effects on sexual activities is definitely to the advantage of the patients .

A thorough QT study to evaluate the QTc prolongation potential of two neuropsychiatric drugs, quetiapine and escitalopram, in healthy volunteers.

Science.gov (United States)

Kim, Anhye; Lim, Kyoung Soo; Lee, Howard; Chung, Hyewon; Yoon, Seo Hyun; Yu, Kyung-Sang; Cho, Joo-Youn; Jang, In-Jin; Chung, Jae-Yong

2016-07-01

Prolongation of the QT interval on an ECG is a surrogate marker for predicting the proarrhythmic potential of a drug under development. The aim of this study was to evaluate the QTc prolongation potential of two neuropsychiatric drugs, quetiapine immediate release (IR) and escitalopram, in healthy individuals. This was a randomized, open-label, 4×4 Williams crossover study, with four single-dose treatments [placebo, 400 mg moxifloxacin (positive control), 20 mg escitalopram, and 100 mg quetiapine IR], conducted in 40 healthy volunteers. Serial blood samples for pharmacokinetics and ECG were collected. Individually, RR-corrected QTc intervals (QTcI) and placebo-adjusted changes from baseline values of QTcI (ΔΔQTcI) were evaluated. Lower-bound values of the one-sided 95% confidence interval for ΔΔQTcI of moxifloxacin with more than 5 ms confirmed the sensitivity of the assay. The maximum upper bound 95% confidence interval for the ΔΔQTcI of quetiapine IR and escitalopram was 13.7 and 10.5 ms, with mean estimates of 10.2 and 6.9 ms, respectively. Peak effects of moxifloxacin and quetiapine IR on ΔΔQTcI were observed at approximately time to maximum concentration (Tmax), whereas that of escitalopram was observed 3 h after Tmax. The concentration-ΔΔQTcI relationships of quetiapine IR and escitalopram were relatively flat, as compared with that of moxifloxacin. The results demonstrated the validity of trial methodology and that quetiapine IR and escitalopram caused QT prolongation in healthy individuals. In addition, hysteresis of escitalopram-induced QTc prolongation. These results indicate that higher doses of these drugs could lead to greater QT prolongation in a dose-response manner.

Effect of Tribulus terrestris on Haloperidol-induced Catalepsy in Mice

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Nishchal, B. S.; Rai, S.; Prabhu, M. N.; Ullal, Sheetal D.; Rajeswari, S.; Gopalakrishna, H. N.

2014-01-01

Haloperidol, an antipsychotic drug, leads to the development of a behavioural state called catalepsy, in which the animal is not able to correct an externally imposed posture. In the present study we have attempted to evaluate the anticataleptic effect of Tribulus terrestris on haloperidol-induced catalepsy in albino mice. Mice were allocated to four groups, each group containing six animals. Both, the test drug, Tribulus terrestris and the standard drug trihexyphenidyl were uniformly suspended in 1% gum acacia solution. Catalepsy was induced in mice with haloperidol (1.0 mg/kg, intraperitoneally). The first group received the vehicle (10 ml/kg, orally), the second group received trihexyphenidyl (10 mg/kg, orally) and the remaining two groups received Tribulus terrestris (100, 200 mg/kg, orally). The animals were assessed after single and repeated dose administration for ten days, 30 min prior to haloperidol, using standard bar test. The result of the present study demonstrates Tribulus terrestris has a protective effect against haloperidol-induced catalepsy, which is comparable to the standard drug used for the same purpose. Our study indicates Tribulus terrestris can be used to prevent haloperidol-induced extrapyramidal side effects. PMID:25593394

Effect of Tribulus terrestris on Haloperidol-induced Catalepsy in Mice.

Science.gov (United States)

Nishchal, B S; Rai, S; Prabhu, M N; Ullal, Sheetal D; Rajeswari, S; Gopalakrishna, H N

2014-01-01

Haloperidol, an antipsychotic drug, leads to the development of a behavioural state called catalepsy, in which the animal is not able to correct an externally imposed posture. In the present study we have attempted to evaluate the anticataleptic effect of Tribulus terrestris on haloperidol-induced catalepsy in albino mice. Mice were allocated to four groups, each group containing six animals. Both, the test drug, Tribulus terrestris and the standard drug trihexyphenidyl were uniformly suspended in 1% gum acacia solution. Catalepsy was induced in mice with haloperidol (1.0 mg/kg, intraperitoneally). The first group received the vehicle (10 ml/kg, orally), the second group received trihexyphenidyl (10 mg/kg, orally) and the remaining two groups received Tribulus terrestris (100, 200 mg/kg, orally). The animals were assessed after single and repeated dose administration for ten days, 30 min prior to haloperidol, using standard bar test. The result of the present study demonstrates Tribulus terrestris has a protective effect against haloperidol-induced catalepsy, which is comparable to the standard drug used for the same purpose. Our study indicates Tribulus terrestris can be used to prevent haloperidol-induced extrapyramidal side effects.

[{sup 18}F]haloperidol binding in baboon brain in vivo

Energy Technology Data Exchange (ETDEWEB)

Yousef, Khalil A; Fowler, Joanna S; Volkow, Nora D; Dewey, Stephen L; Shea, Colleen; Schlyer, David J; Gatley, S John; Logan, Jean; Wolf, Alfred P

1996-01-01

The binding of [{sup 18}F]haloperidol to dopamine D2 and to sigma recognition sites in baboon brain was examined using positron emission tomography (PET). Studies were performed at baseline and after treatment with either haloperidol (to evaluate saturability), (+)-butaclamol (which has specificity for dopamine D2 receptors) or (-)-butaclamol (which has specificity for sigma sites). Binding was widespread. Treatment with (-)-butaclamol had no effect, whereas (+)-butaclamol selectively reduced the uptake in striatum. Haloperidol increased the clearance rate from all brain regions. These results indicate that the binding profile of [{sup 18}F]haloperidol does not permit the selective examination of either dopamine D2 or sigma sites using PET.

QTc-prolonging drugs and hospitalizations for cardiac arrhythmias

NARCIS (Netherlands)

De Bruin, ML; Hoes, AW; Leufkens, HGM

2003-01-01

Cardiac arrhythmia as an adverse effect of noncardiac drugs has been an issue of growing importance during the past few years. In this population-based study, we evaluated the risk for serious cardiac arrhythmias during the use of several noncardiac QTc-prolonging drugs in day-to-day practice, and

Preventing ICU Subsyndromal Delirium Conversion to Delirium With Low-Dose IV Haloperidol: A Double-Blind, Placebo-Controlled Pilot Study.

Science.gov (United States)

Al-Qadheeb, Nada S; Skrobik, Yoanna; Schumaker, Greg; Pacheco, Manuel N; Roberts, Russel J; Ruthazer, Robin R; Devlin, John W

2016-03-01

To compare the efficacy and safety of scheduled low-dose haloperidol versus placebo for the prevention of delirium (Intensive Care Delirium Screening Checklist ≥ 4) administered to critically ill adults with subsyndromal delirium (Intensive Care Delirium Screening Checklist = 1-3). Randomized, double-blind, placebo-controlled trial. Three 10-bed ICUs (two medical and one surgical) at an academic medical center in the United States. Sixty-eight mechanically ventilated patients with subsyndromal delirium without complicating neurologic conditions, cardiac surgery, or requiring deep sedation. Patients were randomly assigned to receive IV haloperidol 1 mg or placebo every 6 hours until delirium occurred (Intensive Care Delirium Screening Checklist ≥ 4 with psychiatric confirmation), 10 days of therapy had elapsed, or ICU discharge. Baseline characteristics were similar between the haloperidol (n = 34) and placebo (n = 34) groups. A similar number of patients given haloperidol (12/34 [35%]) and placebo (8/34 [23%]) developed delirium (p = 0.29). Haloperidol use reduced the hours per study day spent agitated (Sedation Agitation Scale ≥ 5) (p = 0.008), but it did not influence the proportion of 12-hour ICU shifts patients spent alive without coma (Sedation Agitation Scale ≤ 2) or delirium (p = 0.36), the time to first delirium occurrence (p = 0.22), nor delirium duration (p = 0.26). Days of mechanical ventilation (p = 0.80), ICU mortality (p = 0.55), and ICU patient disposition (p = 0.22) were similar in the two groups. The proportion of patients who developed corrected QT-interval prolongation (p = 0.16), extrapyramidal symptoms (p = 0.31), excessive sedation (p = 0.31), or new-onset hypotension (p = 1.0) that resulted in study drug discontinuation was comparable between the two groups. Low-dose scheduled haloperidol, initiated early in the ICU stay, does not prevent delirium and has little therapeutic advantage in mechanically ventilated, critically ill adults

Synthesis of no-carrier-added and carrier-added YF-labelled haloperidol

Energy Technology Data Exchange (ETDEWEB)

Farrokhzad, S; Diksic, M

1985-07-01

Fluorine-18 labelled haloperidol ( YF-HP) was synthesized by a fluorine-fluorine exchange reaction on haloperidol, fluorine-chlorine exchange on a chloro-analog of haloperidol, and from YF-labelled p-fluorobenzonitrile prepared by two different exchange reactions. Nucleophilic fluorine was used in the form of tetra n-butylammonium fluoride. The overall radiochemical yield, expressed at the end of syntheses was 5% for exchange in haloperidol and about 2%-3% for exchange in chloroanalog in a 40 min synthesis (from the end of the irradiation). Specific activities up to 1 Ci/mmol for haloperidol and up to 5000 Ci/mmol for chloro-analog as substrates were obtained. The syntheses using p-substituted chloro-and nitro-benzonitriles as starting materials for the exchange reaction gave a product with an average specific activity of about 2000 Ci/mmol and in general an overall radiochemical yield of 5%-10%. Purification of ( YF)haloperidol was done by HPLC on a C-18 column. The radiochemical purity as assessed by thin layer radiochromatography (TLRC) of the final product was at least 95%, with high chemical purity.

Haloperidol 2 mg impairs inhibition but not visuospatial attention.

Science.gov (United States)

Logemann, H N Alexander; Böcker, Koen B E; Deschamps, Peter K H; van Harten, Peter N; Koning, Jeroen; Kemner, Chantal; Logemann-Molnár, Zsófia; Kenemans, J Leon

2017-01-01

The dopaminergic system has been implicated in visuospatial attention and inhibition, but the exact role has yet to be elucidated. Scarce literature suggests that attenuation of dopaminergic neurotransmission negatively affects attentional focusing and inhibition. To the best of our knowledge, this is the first study that evaluated the effect of dopaminergic antagonism on stopping performance. Dopaminergic neurotransmission was attenuated in 28 healthy male participants by using 2 mg haloperidol. A repeated-measures placebo-controlled crossover design was implemented, and performance indices of attention and inhibition were assessed in the visual spatial cueing task (VSC) and stop signal task (SST). Additionally, the effect of haloperidol on motoric parameters was assessed. It was expected that haloperidol as contrasted to placebo would result in a reduction of the "validity effect," the benefit of valid cueing as opposed to invalid cueing of a target in terms of reaction time. Furthermore, an increase in stop signal reaction time (SSRT) in the SST was expected. Results partially confirmed the hypothesis. Haloperidol negatively affected inhibitory motor control in the SST as indexed by SSRT, but there were no indications that haloperidol affected bias or disengagement in the VSC task as indicated by a lack of an effect on RTs. Pertaining to secondary parameters, motor activity increased significantly under haloperidol. Haloperidol negatively affected reaction time variability and errors in both tasks, as well as omissions in the SST, indicating a decreased sustained attention, an increase in premature responses, and an increase in lapses of attention, respectively.

Short QTc Interval in Males with Klinefelter Syndrome-Influence of CAG Repeat Length, Body Composition, and Testosterone Replacement Therapy

DEFF Research Database (Denmark)

Jørgensen, Inger Norlyk; Skakkebaek, Anne; Andersen, Niels Holmark

2015-01-01

BackgroundKlinefelter syndrome (KS) is a sex chromosomal aneuploidy (47,XXY) affecting 1/660 males. Based on findings in Turner syndrome, we hypothesized that electrocardiogram (ECG) abnormalities would be present in males with KS. ObjectiveTo investigate ECGs in males with KS and compare...... syndrome was determined in participants with a QTc ... interval comparable to controls. No mutations in genes related to short QT syndrome were found. ConclusionWe found short QTc interval in males with KS, with further shortening of the QTc interval by T. These results suggest that genes on the X chromosome could be involved in regulation of the QTc interval...

Quality of life and response of negative symptoms in schizophrenia to haloperidol and the atypical antipsychotic remoxipride. The Canadian Remoxipride Group.

Science.gov (United States)

Awad, A G; Lapierre, Y D; Angus, C; Rylander, A

1997-07-01

In a large, multicenter, double-blind study of the effect of haloperidol and the atypical antipsychotic remoxipride on improvement of negative symptoms in schizophrenia, quality of life was also assessed using a modified version of the Sickness Impact Profile (SIP). Compared with previous studies, this study had a longer duration (28 weeks), and the dose of the comparator, haloperidol, was much lower. At the end of the study, compared with the baseline, both treatment groups reported comparable improvement in negative symptoms as defined by the protocol (at least 20% improvement). Similarly, both groups showed comparable changes on global and multidimensional self-assessments of quality of life. All the subfactors of the modified version of the SIP were similar in both groups, except for the subfactor that relates to alertness behavior, which possibly reflects remoxipride's lack of any sedating properties compared with haloperidol. This study presents an approach for inclusion of quality of life as an outcome measure in the design of clinical trials of new antipsychotic medications.

Is topical haloperidol a useful glaucoma treatment?

OpenAIRE

Lavin, M. J.; Andrews, V.

1986-01-01

A randomised, double blind, single dose study of topical haloperidol, a dopamine receptor blocking drug, was performed on 20 healthy volunteers. After its administration a modest reduction in intraocular pressure was recorded over the six-hour study period, but the difference was not significant at the p less than 0.05 level. Although dopamine blocking agents are effective in reducing intraocular pressure in experimental animals, topical haloperidol appears unlikely to be clinically useful in...

Haloperidol plasmatic levels and their clinical response to the treatment

International Nuclear Information System (INIS)

Cabranes, J.A.; Almoguera, I.; Santos, J.L.; Prieto, P.; Ramos, J.A.

1988-01-01

Schizophrenic patients were treated with haloperidol. Their haloperidol levels in plasma were determined with radioimmunoassay (RIA) and radioreceptor assay (RRA). The results obtained are compared with the clinical improvement. (M.C.B.)

Haloperidol for long-term aggression in psychosis.

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Khushu, Abha; Powney, Melanie J

2016-11-27

Psychotic disorders can lead some people to become agitated. Characterised by restlessness, excitability and irritability, this can result in verbal and physically aggressive behaviour - and both can be prolonged. Aggression within the psychiatric setting imposes a significant challenge to clinicians and risk to service users; it is a frequent cause for admission to inpatient facilities. If people continue to be aggressive it can lengthen hospitalisation. Haloperidol is used to treat people with long-term aggression. To examine whether haloperidol alone, administered orally, intramuscularly or intravenously, is an effective treatment for long-term/persistent aggression in psychosis. We searched the Cochrane Schizophrenia Group Trials Register (July 2011 and April 2015). We included randomised controlled trials (RCT) or double blind trials (implying randomisation) with useable data comparing haloperidol with another drug or placebo for people with psychosis and long-term/persistent aggression. One review author (AK) extracted data. For dichotomous data, one review author (AK) calculated risk ratios (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a fixed-effect model. One review author (AK) assessed risk of bias for included studies and created a 'Summary of findings' table using GRADE. We have no good-quality evidence of the absolute effectiveness of haloperidol for people with long-term aggression. One study randomising 110 chronically aggressive people to three different antipsychotic drugs met the inclusion criteria. When haloperidol was compared with olanzapine or clozapine, skewed data (n=83) at high risk of bias suggested some advantage in terms of scale scores of unclear clinical meaning for olanzapine/clozapine for 'total aggression'. Data were available for only one other outcome, leaving the study early. When compared with other antipsychotic drugs, people allocated to haloperidol were no more likely to leave the study

Effects of phenobarbital and levetiracetam on PR and QTc intervals in patients with post-stroke seizure.

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Siniscalchi, Antonio; Scaglione, Francesco; Sanzaro, Enzo; Iemolo, Francesco; Albertini, Giorgio; Quirino, Gianluca; Manes, Maria Teresa; Gratteri, Santo; Mercuri, Nicola Biagio; De Sarro, Giovambattista; Gallelli, Luca

2014-12-01

Sudden unexplained/unexpected death (SUDEP) is related to high mortality in patients with epilepsy. The prolongation of QT interval, involved in cardiac arrhythmia-related SUDEP, may be precipitated by antiepileptic drugs (AEDs). In this study, we evaluated the effects of phenobarbital and levetiracetam on PR-QTc intervals in patients with post-stroke seizures. We performed an open-label, parallel group, prospective, multicenter study between June 2009 and December 2013 in patients older than 18 years of age with a clinical diagnosis of post-stroke seizure and treated with phenobarbital or levetiracetam. In order to exclude a role of cerebral post-stroke injury on modulation of PR and QTc intervals, patients with cerebral post-stroke injury and without seizures were also enrolled as controls. Interictal electrocardiography analysis revealed no significant difference in PR interval between patients treated with an AED (n = 49) and control patients (n = 50) (181.25 ± 12.05 vs. 182.4 ± 10.3 ms; p > 0.05). In contrast, a significantly longer QTc interval was recorded in patients treated with an AED compared with control patients (441.2 ± 56.6 vs. 396.8 ± 49.3 ms; p phenobarbital showed a significantly longer QTc interval than patients treated with levetiracetam (460.0 ± 57.2 vs. 421.5 ± 50.1 ms; p phenobarbital prolonged QTc interval more so than levetiracetam.

Gender-Specific Differences in Low-Dose Haloperidol Response for Prevention of Postoperative Nausea and Vomiting: A Register-Based Cohort Study.

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Brettner, Florian; Janitza, Silke; Prüll, Kathrin; Weninger, Ernst; Mansmann, Ulrich; Küchenhoff, Helmut; Jovanovic, Alexander; Pollwein, Bernhard; Chappell, Daniel; Zwissler, Bernhard; von Dossow, Vera

2016-01-01

Postoperative nausea and vomiting (PONV) is one of the most common and distressing complications after general anesthesia and surgery, with young non-smoking females receiving postoperative opioids being high-risk patients. This register-based study aims to evaluate the effect of low-dose haloperidol (0.5 mg intravenously) directly after induction of general anesthesia to reduce the incidence of PONV in the postoperative anesthesiological care unit (PACU). Multivariable regression models were used to investigate the association between low-dose haloperidol and the occurrence of PONV using a patient registry containing 2,617 surgical procedures carried out at an university hospital. Haloperidol 0.5 mg is associated with a reduced risk of PONV in the total collective (adjusted odds ratio = 0.75, 95% confidence interval: [0.56, 0.99], p = 0.05). The results indicate that there is a reduced risk in male patients (adjusted odds ratio = 0.45, 95% confidence interval: [0.28, 0.73], p = 0.001) if a dose of 0.5 mg haloperidol was administered while there seems to be no effect in females (adjusted odds ratio = 1.02, 95% confidence interval: [0.71, 1.46], p = 0.93). Currently known risk factors for PONV such as female gender, duration of anesthesia and the use of opioids were confirmed in our analysis. This study suggests that low-dose haloperidol has an antiemetic effect in male patients but has no effect in female patients. A confirmation of the gender-specific effects we have observed in this register-based cohort study might have major implications on clinical daily routine.

The Effect of the Type of Hemodialysis Buffer on the QTc Interval in Patients on Chronic Hemodialysis

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Reza Hekmat

2009-03-01

Full Text Available Background: Identifying the sources of variation in QTc measurementsis important for preventing arrhythmias during and afterhemodialysis. The present study was designed to determine thecorrelation between the type of hemodialysis buffer and thechanges in QTc interval in patients on chronic hemodialysis.Methods: Fifty-nine patients on chronic hemodialysis whoreferred in winter 2007 to hemodialysis centers of Ghaem andHashemi Nejad hospitals, in Mashhad, Iran, were divided intotwo groups according to their last dialysate buffer: acetate orbicarbonate. Electrocardiography, arterial blood gas parameters,serum K+, Na+, ionized calcium, and albumin levels weremeasured prior to and after hemodialysis in all patients.Results: All arterial blood gas parameters and serum electrolytesconcentrations were increased except K+ levels that weresignificantly decreased with hemodialysis. PCO2 and QTc intervalswere slightly increased in all patients, however thisincrease was not statistically significant. We found that thetype of dialysate affected the QTc interval, HCO3, base excess,base excess of extra cellular fluid, and base bufferchanges with no effect on ionized calcium, pH, PCO2, andserum albumin concentration. QTc interval was prolonged byusing bicarbonate and shortened by using acetate dialysatebuffer. We found no correlation between the variations of QTcinterval and serum electrolytes or arterial blood gas parametersin either group.Conclusion: Bicarbonate buffer use in hemodialysis prolongedQTc interval and acetate buffer shortened it. This effectis independent of serum electrolytes and pH changes duringhemodialysis. The effect of bicarbonate buffer is probablydue to more tolerability of ultra filtration, more effectiveedema reduction and augmented body electro-conductivity.

Effects of Haloperidol on Responding Maintained with Food and Sucrose-Water

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Carlos F. Aparicio

2010-02-01

Full Text Available The “hedonic” value of reinforcers is mediated by dopamine. Accordingly,haloperidol diminishes the value of reinforcers, by interfering with the emission of operant behaviors. Alternatively, the interference of dopamine transmission does not prevent animals from eating food. Thus, reinforcers remain intact after the administration of haloperidol. We assessed these possibilities with eight Wistar rats and two types of reinforcers, food-pellets and sucrose-water, delivered under multiple reinforcement schedules. Ingeneral, lever presses maintained by food-pellets were higher than those maintained by sucrose-water. Haloperidol produced dose-related decreases in lever presses and obtained reinforcers. Different doses had no effect on the number of lever presses. Subcutaneous administrations of haloperidol produced higher decreases in lever presses than intra-peritoneal administrations. Decreases in lever pressing were not necessarily accompanied by substantial reductions in obtained food-pellets and sucrose-water reinforcers; underthe effects of haloperidol rats continued to produce a considerable number of both types of reinforcers.

The effects of thioridazine on the QTc interval - cardiovascular safety in a South African setting

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Cathlene Seller

2005-09-01

Full Text Available Background. Thioridazine has long been used as a first-line antipsychotic in South Africa without any apparent problems. Recently the American Food and Drug Administration (FDA and Novartis have warned of potentially lethal arrhythmias that may result from the use of thioridazine. Abnormal QT-interval prolongation on the electrocardiogram (ECG seems to be the most reliable indicator of risk of arrhythmias, such as torsade de pointes and ventricular fibrillation. Objective. The purpose of this study was to determine whether these warnings are of clinical relevance in a setting where there are already a limited number of antipsychotics available. Method. Thirty hospitalised subjects who required switching from a high-potency to a low-potency antipsychotic were included. All subjects were commenced on thioridazine 300 mg per day and had an ECG 1 week after initiation and 48 hours after each dose adjustment. QTc was determined using Bazett’s formula. Results. Thioridazine induced a significant increase (p = 0.0001 in QTc interval from baseline values of 400.6 (± 27.3 milliseconds to 429.1 (± 44.2 milliseconds. The QTc interval increased to above 450 milliseconds in 7 subjects (23% and thioridazine was discontinued in 2 subjects because of a QTc interval greater or equal to 500 milliseconds. Conclusion. Thioridazine caused a significant, although asymptomatic, increase in QTc interval in almost one-quarter of subjects who received the medication as second-line treatment. Thioridazine should no longer be used as a first-line treatment and if used it should be accompanied by regular ECG monitoring.

Interleukin-1β gene variants are associated with QTc interval prolongation following cardiac surgery: a prospective observational study.

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Kertai, Miklos D; Ji, Yunqi; Li, Yi-Ju; Mathew, Joseph P; Daubert, James P; Podgoreanu, Mihai V

2016-04-01

We characterized cardiac surgery-induced dynamic changes of the corrected QT (QTc) interval and tested the hypothesis that genetic factors are associated with perioperative QTc prolongation independent of clinical and procedural factors. All study subjects were ascertained from a prospective study of patients who underwent elective cardiac surgery during August 1999 to April 2002. We defined a prolonged QTc interval as > 440 msec, measured from 24-hr pre- and postoperative 12-lead electrocardiograms. The association of 37 single nucleotide polymorphisms (SNPs) in 21 candidate genes -involved in modulating arrhythmia susceptibility pathways with postoperative QTc changes- was investigated in a two-stage design with a stage I cohort (n = 497) nested within a stage II cohort (n = 957). Empirical P values (Pemp) were obtained by permutation tests with 10,000 repeats. After adjusting for clinical and procedural risk factors, we selected four SNPs (P value range, 0.03-0.1) in stage I, which we then tested in the stage II cohort. Two functional SNPs in the pro-inflammatory cytokine interleukin-1β (IL1β), rs1143633 (odds ratio [OR], 0.71; 95% confidence interval [CI], 0.53 to 0.95; Pemp = 0.02) and rs16944 (OR, 1.31; 95% CI, 1.01 to 1.70; Pemp = 0.04), remained independent predictors of postoperative QTc prolongation. The ability of a clinico-genetic model incorporating the two IL1B polymorphisms to classify patients at risk for developing prolonged postoperative QTc was superior to a clinical model alone, with a net reclassification improvement of 0.308 (P = 0.0003) and an integrated discrimination improvement of 0.02 (P = 0.000024). The results suggest a contribution of IL1β in modulating susceptibility to postoperative QTc prolongation after cardiac surgery.

Multiple neurotoxic effects of haloperidol resulting in neuronal death.

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Nasrallah, Henry A; Chen, Alexander T

2017-08-01

Several published studies have reported an association between antipsychotic medications, especially first-generation agents, and a decline in gray matter volume. This prompted us to review the possible neurotoxic mechanisms of first-generation antipsychotics (FGAs), especially haloperidol, which has been widely used over the past several decades. A PubMed search was conducted using the keywords haloperidol, antipsychotic, neurotoxicity, apoptosis, oxidative stress, and neuroplasticity. No restrictions were placed on the date of the articles or language. Studies with a clearly described methodology were included. Animal, cell culture, and human tissue studies were identified. Thirty reports met the criteria for the search. All studies included haloperidol; a few also included other FGAs (fluphenazine and perphenazine) and/or second-generation agents (SGAs) (aripiprazole, paliperidone, and risperidone). A neurotoxic effect of haloperidol and other FGAs was a common theme across all studies. Minimal (mainly at high doses) or no neurotoxic effects were noted in SGAs. A review of the literature suggests that haloperidol exerts measurable neurotoxic effects at all doses via many molecular mechanisms that lead to neuronal death. A similar effect was observed in 2 other FGAs, but the effect in SGAs was much smaller and occurred mainly at high doses. A stronger binding to serotonin 5HT-2A receptors than to dopamine D2 receptors may have a neuroprotective effect among SGAs. Further studies are warranted to confirm these findings.

Brain Levels of the Neurotoxic Pyridinium Metabolite HPP+ and Extrapyramidal Symptoms in Haloperidol-Treated Mice

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Crowley, James J.; Ashraf-Khorassani, Mehdi; Castagnoli, Neal; Sullivan, Patrick F.

2013-01-01

The typical antipsychotic haloperidol is a highly effective treatment for schizophrenia but its use is limited by a number of serious, and often irreversible, motor side effects. These adverse drug reactions, termed extrapyramidal syndromes (EPS), result from an unknown pathophysiological mechanism. One theory relates to the observation that the haloperidol metabolite HPP+ (4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]-pyridinium) is structurally similar to MPP+ (1-methyl-4-phenylpyridinium), a neurotoxin responsible for an irreversible neurodegenerative condition similar to Parkinson's disease. To determine whether HPP+ contributes to haloperidol-induced EPS, we measured brain HPP+ and haloperidol levels in strains of mice at high (C57BL/6J and NZO/HILtJ) and low (BALB/cByJ and PWK/PhJ) liability to haloperidol-induced EPS following chronic treatment (7–10 adult male mice per strain). Brain levels of HPP+ and the ratio of HPP+ to haloperidol were not significantly different between the haloperidol-sensitive and haloperidol-resistant strain groups (P = 0.50). Within each group, however, strain differences were seen (P haloperidol treatment, the findings from this study are physiologically relevant to humans. The results suggest that strain differences in steady-state HPP+ levels do not explain sensitivity to haloperidol-induced EPS in the mice we studied. PMID:24107597

Haloperidol inhibits the development of atherosclerotic lesions in LDL receptor knockout mice.

Science.gov (United States)

van der Sluis, Ronald J; Nahon, Joya E; Reuwer, Anne Q; Van Eck, Miranda; Hoekstra, Menno

2015-05-01

Antipsychotic drugs have been shown to modulate the expression of ATP-binding cassette transporter A1 (ABCA1), a key factor in the anti-atherogenic reverse cholesterol transport process, in vitro. Here we evaluated the potential of the typical antipsychotic drug haloperidol to modulate the cholesterol efflux function of macrophages in vitro and their susceptibility to atherosclerosis in vivo. Thioglycollate-elicited peritoneal macrophages were used for in vitro studies. Hyperlipidaemic low-density lipoprotein (LDL) receptor knockout mice were implanted with a haloperidol-containing pellet and subsequently fed a Western-type diet for 5 weeks to induce the development of atherosclerotic lesions in vivo. Haloperidol induced a 54% decrease in the mRNA expression of ABCA1 in peritoneal macrophages. This coincided with a 30% decrease in the capacity of macrophages to efflux cholesterol to apolipoprotein A1. Haloperidol treatment stimulated the expression of ABCA1 (+51%) and other genes involved in reverse cholesterol transport, that is, CYP7A1 (+98%) in livers of LDL receptor knockout mice. No change in splenic ABCA1 expression was noted. However, the average size of the atherosclerotic size was significantly smaller (-31%) in the context of a mildly more atherogenic metabolic phenotype upon haloperidol treatment. More importantly, haloperidol markedly lowered MCP-1 expression (-70%) and secretion (-28%) by peritoneal macrophages. Haloperidol treatment lowered the susceptibility of hyperlipidaemic LDL receptor knockout mice to develop atherosclerotic lesions. Our findings suggest that the beneficial effect of haloperidol on atherosclerosis susceptibility can be attributed to its ability to inhibit macrophage chemotaxis. © 2015 The British Pharmacological Society.

No difference in frontal cortical activity during an executive functioning task after acute doses of aripiprazole and haloperidol

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Ingeborg eBolstad

2015-05-01

Full Text Available Background: Aripiprazole is an atypical antipsychotic drug that is characterized by partial dopamine D2 receptor agonism. Its pharmacodynamic profile is proposed to be beneficial in the treatment of cognitive impairment, which is prevalent in psychotic disorders. This study compared brain activation characteristics produced by aripiprazole with that of haloperidol, a typical D2 receptor antagonist, during a task targeting executive functioning.Methods: Healthy participants received an acute oral dose of haloperidol, aripiprazole or placebo before performing an executive functioning task while blood-oxygen-level-dependent (BOLD functional magnetic resonance imaging (fMRI was carried out. Results: There was a tendency towards reduced performance in the aripiprazole group compared to the two other groups. The image analysis yielded a strong task-related BOLD-fMRI response within each group. An uncorrected between-group analysis showed that aripiprazole challenge resulted in stronger activation in the frontal and temporal gyri and the putamen compared with haloperidol challenge, but after correcting for multiple testing there was no significant group difference. Conclusion: No significant group differences between aripiprazole and haloperidol in frontal cortical activation were obtained when corrected for multiple comparisons.This study is registered in ClinicalTrials.gov (identifier: 2009-016222-14; https://clinicaltrials.gov/.

An acute oral intoxication with haloperidol decanoate : A case report

NARCIS (Netherlands)

Dekkers, Bart G J; Eck, Ruben J; Ter Maaten, Jan C; Touw, Daniël J

2017-01-01

Haloperidol decanoate is a typical antipsychotic drug used as maintenance therapy for schizophrenia and mood disorders formulated as an ester for intramuscular injection. Cases of oral haloperidol decanoate intoxications have not been described in literature. In this report, we present for the first

Pharmacologic treatment of acute pediatric methamphetamine toxicity.

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Ruha, Anne-Michelle; Yarema, Mark C

2006-12-01

To report our experience with the use of benzodiazepines and haloperidol for sedation of pediatric patients with acute methamphetamine poisoning. We performed a retrospective chart review of 18 pediatric patients who were admitted to an intensive care unit for methamphetamine toxicity from January 1997 to October 2004 and treated with benzodiazepines or haloperidol. Clinical features, dose of drug received, and laboratory test results were noted. Adverse effects from the use of haloperidol such as prolonged QTc, dystonic reactions, and torsades de pointes were recorded. Eighteen patients received a benzodiazepine, the dose of which varied depending on the agent used. Twelve patients also received parenteral haloperidol. No complications developed from the use of either haloperidol or benzodiazepines. In this case series of pediatric patients poisoned with methamphetamine, parenteral benzodiazepines and haloperidol were used to control agitation. No serious adverse effects were observed from the use of these agents.

Co-treatment with imipramine averted haloperidol-instigated tardive dyskinesia: Association with serotonin in brain regions.

Science.gov (United States)

Samad, Noreen; Yasmin, Farzana; Haleem, Darakhshan Jabeen

2016-11-01

Outcome of imipramine (IMI) treatment was scrutinized on progression of haloperidol instigated tardive dyskinesia (TD). 0.2 mg/kg/rat dosage of haloperidol provided orally to rats for 2 weeks enhanced vacuous chewing movements that escalated when the process proceeded for 5 weeks. Following 2 weeks co-injection 5 mg/kg dosage of IMI was diminished haloperidol-instigated VCMs and fully averted following five weeks. The potency of 8-OH-DPAT-instigated locomotor activity exhibited higher in saline+haloperidol treated rats while not observed in IMI+ haloperidol treated rats. 8-OH-DPAT-instigated low 5-hydroxytryptamine (5-HT; serotonin) metabolism was higher in saline+ haloperidol treated rats when compare to IMI+ haloperidol treated rats in both regions of brain (striatum and midbrain). It is recommended that IMI possibly competent in averting TD, in cases receiving treatment to antipsychotics.

P6 Electroacupuncture Improved QTc Interval Prolongation by Upregulation of Connexin43 in Droperidol Treated Rats

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Feng Zhao

2014-01-01

Full Text Available Aim. This study investigated the effect of P6 EA on droperidol-induced QTc interval prolongation and Cx43 expression in ventricular muscle of rats. Methods. Twenty-four rats were randomly divided into control group (C, droperidol group (D, or EA group (E. C group rats were injected with normal saline. D group rats were injected with droperidol 0.13 mg/kg. E group rats were pretreated with EA at left P6 acupoint for 30 min and then injected with droperidol (0.13 mg/kg. QTc intervals were recorded at lead II in ECG within 120 min. Cx43 expression was measured by RT-PCR and western blotting. Result. Droperidol significantly prolonged QTc intervals compared with controls at 5 min, 10 min, 15 min, and 30 min (P0.05. Conclusion. P6 EA could improve QTc interval prolongation induced by droperidol, which may relate to upregulation of Cx43 mRNA and protein. Antiemetic dose of droperidol had minor effects on Cx43 mRNA and protein expression at 120 min.

New in vitro model for proarrhythmia safety screening: IKs inhibition potentiates the QTc prolonging effect of IKr inhibitors in isolated guinea pig hearts.

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Kui, Péter; Orosz, Szabolcs; Takács, Hedvig; Sarusi, Annamária; Csík, Norbert; Rárosi, Ferenc; Csekő, Csongor; Varró, András; Papp, Julius Gy; Forster, Tamás; Farkas, Attila S; Farkas, András

2016-01-01

Preclinical in vivo QT measurement as a proarrhythmia essay is expensive and not reliable enough. The aim of the present study was to develop a sensitive, cost-effective, Langendorff perfused guinea pig heart model for proarrhythmia safety screening. Low concentrations of dofetilide and cisapride (inhibitors of the rapid delayed rectifier potassium current, IKr) were tested alone and co-perfused with HMR-1556 (inhibitor of the slow delayed rectifier potassium current, IKs) in Langendorff perfused guinea pig hearts. The electrocardiographic rate corrected QT (QTc) interval, the Tpeak-Tend interval and the beat-to-beat variability and instability (BVI) of the QT interval were determined in sinus rhythm. Dofetilide and HMR-1556 alone or co-perfused, prolonged the QTc interval by 20±2%, 10±1% and 55±10%, respectively. Similarly, cisapride and HMR-1556 alone or co-perfused, prolonged the QTc interval by 11±3%, 11±4% and 38±6%, respectively. Catecholamine-induced fast heart rate abolished the QTc prolonging effects of the IKr inhibitors, but augmented the QTc prolongation during IKs inhibition. None of the drug perfusions increased significantly the Tpeak-Tend interval and the sinus BVI of the QT interval. IKs inhibition increased the QTc prolonging effect of IKr inhibitors in a super-additive (synergistic) manner, and the QTc interval was superior to other proarrhythmia biomarkers measured in sinus rhythm in isolated guinea pig hearts. The effect of catecholamines on the QTc facilitated differentiation between IKr and IKs inhibitors. Thus, QTc measurement in Langendorff perfused guinea pig hearts with pharmacologically attenuated repolarization reserve and periodic catecholamine perfusion seems to be suitable for preclinical proarrhythmia screening. Copyright © 2016 Elsevier Inc. All rights reserved.

Haloperidol for psychosis-induced aggression or agitation (rapid tranquillisation).

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Ostinelli, Edoardo G; Brooke-Powney, Melanie J; Li, Xue; Adams, Clive E

2017-07-31

Haloperidol used alone is recommended to help calm situations of aggression or agitation for people with psychosis. It is widely accessible and may be the only antipsychotic medication available in limited-resource areas. To examine whether haloperidol alone is an effective treatment for psychosis-induced aggression or agitation, wherein clinicians are required to intervene to prevent harm to self and others. We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials (26th May 2016). This register is compiled by systematic searches of major resources (including AMED, BIOSIS CINAHL, Embase, MEDLINE, PsycINFO, PubMed, and registries of clinical trials) and their monthly updates, handsearches, grey literature, and conference proceedings, with no language, date, document type, or publication status limitations for inclusion of records into the register. Randomised controlled trials (RCTs) involving people exhibiting aggression and/or agitation thought to be due to psychosis, allocated rapid use of haloperidol alone (by any route), compared with any other treatment. Outcomes of interest included tranquillisation or asleep by 30 minutes, repeated need for rapid tranquillisation within 24 hours, specific behaviours (threat or injury to others/self), adverse effects. We included trials meeting our selection criteria and providing useable data. We independently inspected all citations from searches, identified relevant abstracts, and independently extracted data from all included studies. For binary data we calculated risk ratio (RR), for continuous data we calculated mean difference (MD), and for cognitive outcomes we derived standardised mean difference (SMD) effect sizes, all with 95% confidence intervals (CI) and using a fixed-effect model. We assessed risk of bias for the included studies and used the GRADE approach to produce 'Summary of findings' tables which included our pre-specified main outcomes of interest. We found nine new RCTs from the

Intramuscular ziprasidone versus haloperidol for managing agitation in Chinese patients with schizophrenia.

Science.gov (United States)

Zhang, Hongyan; Wang, Gang; Zhao, Jingping; Xie, Shiping; Xu, Xiufeng; Shi, Jianguo; Deng, Hehuang; Li, Keqing; Gao, Chengge; Wang, Xiaoping; Vanderburg, Douglas; Pan, Sharon; Tang, Haiyun; Shu, Liang; Karayal, Onur N

2013-04-01

Intramuscular (IM) antipsychotics are preferred for efficient control of agitation symptoms. Previous studies have demonstrated that IM ziprasidone is efficacious and safe for treatment of agitation in schizophrenia. However, clinicians now recognize that racial differences may contribute to altered therapeutic response and tolerability. This study compared the efficacy and tolerability of IM ziprasidone versus IM haloperidol for the management of agitation in Chinese subjects with schizophrenia. Subjects with acute schizophrenia were randomized to either ziprasidone (n = 189, 10 to 20 mg as required up to a maximum of 40 mg/d) or haloperidol (n = 187, 5 mg every 4 to 8 hours to a maximum of 20 mg/d) for 3 days. Psychiatric assessments and adverse events were assessed at baseline, 2, 4, 24, 48, and 72 hours. In the ziprasidone group, 2.1% of subjects discontinued versus 3.7% in the haloperidol group. The least squares mean change (SE) from baseline to 72 hours in Brief Psychiatry Rating Scale total score was -17.32 (0.7) for ziprasidone (n = 167) and -18.44 (0.7) for haloperidol (n = 152), with a 95% confidence interval treatment difference of -0.7 to 2.9. Fewer subjects experienced adverse events after ziprasidone (n = 54, 28.6%) than haloperidol (n = 116, 62.0%), with a notably higher incidence of extrapyramidal symptoms in the haloperidol group (n = 69, 36.9%) compared to the ziprasidone group (n = 4, 2.1%). For controlling agitation in schizophrenia in this Chinese study, ziprasidone had a favorable tolerability profile and comparable efficacy and safety compared to haloperidol.

Blood to brain iron uptake in one Rhesus monkey using [Fe-52]-citrate and positron emission tomography (PET): influence of haloperidol

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Leenders, K L [Paul Scherrer Inst., Villigen (Switzerland); [Neurology Dept., Univ. Hospital, Zuerich (Switzerland); Antonini, A; Schwarzbach, R; Smith-Jones, P; Reist, H [Paul Scherrer Inst., Villigen (Switzerland); Youdim, M [Pharmacology Dept., Technion, Haifa (Israel); Henn, V [Neurology Dept., Univ. Hospital, Zuerich (Switzerland)

1994-12-31

Iron is highly concentrated in the basal ganglia of the brain. The involvement of cerebral iron and its handling systems in neurodegenerative brain diseases like Parkinson`s disease and tardive dyskinesia is currently under close investigation. There is evidence from animal studies that neuroleptics can increase iron uptake into brain. This effect appeared to be due to alteration of blood-brain barrier transport by the neuroleptics, particularly chlorpromazine and haloperidol, but not clozapine. We have investigated one Rhesus monkey using positron emission tomography (PET) and [Fe-52]-citrate before and during haloperidol administration. After drug withdrawal during a period of 1.5 year the investigation procedure was repeated. The results show that in the investigated monkey haloperidol induces a reversible marked increase of iron transport across the blood brain barrier concomitant with a large increase in elimination rate of the tracer from the blood. (author).

Blood to brain iron uptake in one Rhesus monkey using [Fe-52]-citrate and positron emission tomography (PET): influence of haloperidol

International Nuclear Information System (INIS)

Leenders, K.L.; Antonini, A.; Schwarzbach, R.; Smith-Jones, P.; Reist, H.; Youdim, M.; Henn, V.

1994-01-01

Iron is highly concentrated in the basal ganglia of the brain. The involvement of cerebral iron and its handling systems in neurodegenerative brain diseases like Parkinson's disease and tardive dyskinesia is currently under close investigation. There is evidence from animal studies that neuroleptics can increase iron uptake into brain. This effect appeared to be due to alteration of blood-brain barrier transport by the neuroleptics, particularly chlorpromazine and haloperidol, but not clozapine. We have investigated one Rhesus monkey using positron emission tomography (PET) and [Fe-52]-citrate before and during haloperidol administration. After drug withdrawal during a period of 1.5 year the investigation procedure was repeated. The results show that in the investigated monkey haloperidol induces a reversible marked increase of iron transport across the blood brain barrier concomitant with a large increase in elimination rate of the tracer from the blood. (author)

Serum albumin and the haloperidol pharmacokinectics. A study using a computational model

Science.gov (United States)

de Morais e Coura, Carla Patrícia; Paulino, Erica Tex; Cortez, Celia Martins; da Silva Fragoso, Viviane Muniz

2016-12-01

Here we are studying the binding of haloperidol with human and bovine sera albumins applying a computational model, based on spectrofluorimetry, statistical and mathematical knowledge. Haloperidol is one of the oldest antipsychotic drug in use for therapy of patients with acute and chronic schizophrenia. It was found that the fluorescence of HSA was quenched in 18.0 (± 0.2)% and for BSA it was 24.0 (± 0.9)%, for a ratio of 1/1000 of haloperidol/albumin. Results suggested that the primary binding site is located in the subdomain IB. Quenching constants of the albumin fluorescence by haloperidol were in the order of 107, approximately 100-fold higher than that found for risperidone, and about 1000-fold higher than that estimated for chlorpromazine and sulpiride.

Lack of an Effect of Standard and Supratherapeutic Doses of Linezolid on QTc Interval Prolongation▿†

Science.gov (United States)

Damle, Bharat; LaBadie, Robert R.; Cuozzo, Cheryl; Alvey, Christine; Choo, Heng Wee; Riley, Steve; Kirby, Deborah

2011-01-01

A double-blind, placebo-controlled, four-way crossover study was conducted in 40 subjects to assess the effect of linezolid on corrected QT (QTc) interval prolongation. Time-matched, placebo-corrected QT intervals were determined predose and at 0.5, 1 (end of infusion), 2, 4, 8, 12, and 24 h after intravenous dosing of linezolid 600 and 1,200 mg. Oral moxifloxacin at 400 mg was used as an active control. The pharmacokinetic profile of linezolid was also evaluated. At each time point, the upper bound of the 90% confidence interval (CI) for placebo-corrected QTcF values (i.e., QTc values adjusted for ventricular rate using the correction methods of Fridericia) for linezolid 600 and 1,200-mg doses were 5 ms, indicating that the study was adequately sensitive to assess QTc prolongation. The pharmacokinetic profile of linezolid at 600 mg was consistent with previous observations. Systemic exposure to linezolid increased in a slightly more than dose-proportional manner at supratherapeutic doses, but the degree of nonlinearity was small. At a supratherapeutic single dose of 1,200 mg of linezolid, no treatment-related increase in adverse events was seen compared to 600 mg of linezolid, and no clinically meaningful effects on vital signs and safety laboratory evaluations were noted. PMID:21709083

The synthesis of no-carrier-added and carrier-added 18F-labelled haloperidol

International Nuclear Information System (INIS)

Farrokhzad, S.; Diksic, M.

1985-01-01

Fluorine-18 labelled haloperidol ( 18 F-HP) was synthesized by a fluorine-fluorine exchange reaction on haloperidol, fluorine-chlorine exchange on a chloro-analog of haloperidol, and from 18 F-labelled p-fluorobenzonitrile prepared by two different exchange reactions. Nucleophilic fluorine was used in the form of tetra n-butylammonium fluoride. The overall radiochemical yield, expressed at the end of syntheses was 5% for exchange in haloperidol and about 2%-3% for exchange in chloroanalog in a 40 min synthesis (from the end of the irradiation). Specific activities up to 1 Ci/mmol for haloperidol and up to 5000 Ci/mmol for chloro-analog as substrates were obtained. The syntheses using p-substituted chloro-and nitro-benzonitriles as starting materials for the exchange reaction gave a product with an average specific activity of about 2000 Ci/mmol and in general an overall radiochemical yield of 5%-10%. Purification of [ 18 F]haloperidol was done by HPLC on a C-18 column. The radiochemical purity as assessed by thin layer radiochromatography (TLRC) of the final product was at least 95%, with high chemical purity. (author)

Single Doses up to 800 mg of E-52862 Do Not Prolong the QTc Interval--A Retrospective Validation by Pharmacokinetic-Pharmacodynamic Modelling of Electrocardiography Data Utilising the Effects of a Meal on QTc to Demonstrate ECG Assay Sensitivity.

Science.gov (United States)

Täubel, Jörg; Ferber, Georg; Lorch, Ulrike; Wang, Duolao; Sust, Mariano; Camm, A John

2015-01-01

E-52862 is a Sigma-1 receptor antagonist (S1RA) currently under investigation as a potential analgesic medicine. We successfully applied a concentration-effect model retrospectively to a four-way crossover Phase I single ascending dose study and utilized the QTc shortening effects of a meal to demonstrate assay sensitivity by establishing the time course effects from baseline in all four periods, independently from any potential drug effects. Thirty two healthy male and female subjects were included in four treatment periods to receive single ascending doses of 500 mg, 600 mg or 800 mg of E-52862 or placebo. PK was linear over the dose range investigated and doses up to 600 mg were well tolerated. The baseline electrocardiography (ECG) measurements on Day-1 were time-matched with ECG and pharmacokinetic (PK) samples on Day 1 (dosing day). In this conventional mean change to time-matched placebo analysis, the largest time-matched difference to placebo QTcI was 1.44 ms (90% CI: -4.04, 6.93 ms) for 500 mg; -0.39 ms (90% CI: -3.91, 3.13 ms) for 600 mg and 1.32 ms (90% CI: -1.89, 4.53 ms) for 800 mg of E-52862, thereby showing the absence of any QTc prolonging effect at the doses tested. In addition concentration-effect models, one based on the placebo corrected change from baseline and one for the change of QTcI from average baseline with time as fixed effect were fitted to the data confirming the results of the time course analysis. The sensitivity of this study to detect small changes in the QTc interval was confirmed by demonstrating a shortening of QTcF of -8.1 (90% CI: -10.4, -5.9) one hour and -7.2 (90% CI: -9.4, -5.0) three hours after a standardised meal. EU Clinical Trials Register EudraCT 2010 020343 13.

Radiation-induced increases in sensitivity of cataleptic behavior to haloperidol: possible involvement of prostaglandins

International Nuclear Information System (INIS)

Joseph, J.A.; Kandasamy, S.B.; Hunt, W.A.; Dalton, T.K.; Stevens, S.

1988-01-01

The effects of radiation exposure on haloperidol-induced catalepsy were examined in order to determine whether elevated prostaglandins, through an action on dopaminergic autoreceptors, could be involved in the radiation-induced increase in the potency of this neuroleptic. Cataleptic behavior was examined in animals irradiated with various doses of gamma photons (1-150 Gy) and pretreated with a subthreshold dose of haloperidol (0.1 mg/kg). This approach was chosen to maximize any synergistic effects of radiation and haloperidol. After irradiation with doses less than or equal to 30 Gy, the combined treatment of haloperidol and radiation produced catalepsy, whereas neither treatment alone had an effect. This observed catalepsy could be blocked with prior administration of indomethacin, a prostaglandin synthesis inhibitor. Animals exposed to doses of radiation less than or equal to 50 Gy and no haloperidol, however, displayed apparent catalepsy. This effect was also antagonized by indomethacin. Prostaglandins can induce catalepsy and when administered in subthreshold doses along with subthreshold doses of haloperidol, catalepsy was observed. In order to assess a possible action of prostaglandins and radiation on dopaminergic activity, the functioning of striatal dopaminergic autoreceptors was examined by determining the effects of varying concentrations of haloperidol on the K+-evoked release of dopamine from striatal slices obtained from parallel groups of animals treated as above. Results indicated that sensitivity to haloperidol increased (higher K+-evoked dopamine release) in slices from irradiated or prostaglandin-treated animals and that this increase in sensitivity was blocked by indomethacin

Anti-idiotypes against a monoclonal anti-haloperidol antibody bind to dopamine receptor

International Nuclear Information System (INIS)

Elazar, Z.; Kanety, H.; Schreiber, M.; Fuchs, S.

1988-01-01

Anti-idiotypic antibodies were raised in rabbits by immunization with a monoclonal anti-haloperidol antibody. Some of these anti-idiotypic antibodies bind in a concentration dependent manner to bovine striatal membranes. Following affinity purification, these antibodies inhibit haloperidol binding to striatal membranes and deplete [ 3 H]-spiperone binding sites from a solubilized preparation of striatal membranes. It is thus concluded that these anti-idiotypic antibodies are an internal image of haloperidol and as such can interact with D 2 -dopamine receptors

Reversal of haloperidol-induced tardive vacuous chewing movements and supersensitive somatodendritic serotonergic response by imipramine in rats

International Nuclear Information System (INIS)

Samad, N.; Haleem, D.J.

2013-01-01

The study was designed to test the hypothesis that a decrease in the responsiveness of somatodendritic 5-HT-1A receptors by co- administration of imipramine could reverse the induction of VCMs and supersensitivity at 5-HT-IA receptors by haloperidol. Rats treated with haloperidol 0.2mg/rat/day for 2 weeks induced VCMs with twitching of facial musculature that increased in a time dependent manner as the treatment continued to 5 weeks. Co administration of imipramine (5mg/kg/m1) attenuated haloperidol-induced VCMs after 2 weeks and completely reversed it after 5 weeks. The intensity of 8-hydroxy -2-di(n-propyleamino)tetraline (8-OH-DPAT)-induced locomotion and forepaw treading were greater in saline+haloperidol injected but not in imipramine+haloperidol injected animals. 8-OH-DPAT induced decreases of 5-HT metabolism were greater in saline+haloperidol injected animals but not in imipramine+haloperidol injected animals. The mechanism involved in reversal/attenuation of haloperidol-induced tardive dyskinesia by imipramine is discussed. (author)

Haloperidol, a sigma receptor 1 antagonist, promotes ferroptosis in hepatocellular carcinoma cells.

Science.gov (United States)

Bai, Tao; Wang, Shuai; Zhao, Yipu; Zhu, Rongtao; Wang, Weijie; Sun, Yuling

2017-09-30

Ferroptosis is a novel form of cell death, which is characterized by accumulation of reactive oxygen species (ROS). Sigma 1 receptor (S1R) has been suggested to function in oxidative stress metabolism. Both erastin and sorafenib significantly induced S1R protein expression. Haloperidol strongly promoted erastin- and sorafenib-induced cell death, which was blocked by ferrostatin-1 but not ZVAD-FMK or necrosulfonamide. During ferroptosis, haloperidol substantially increased the cellular levels of Fe 2+ , GSH and lipid peroxidation. Furthermore, several ferroptosis-related protein targets were up-regulated in the absence of haloperidol. Thus, Our study identified an association between haloperidol and ferroptosis for the first time. Our analyses of a combination of drugs may provide a novel strategy of hepatocellular carcinoma (HCC) therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

Contribution of the central histaminergic transmission in the cataleptic and neuroleptic effects of haloperidol.

Science.gov (United States)

Jain, Nishant S; Tandi, Lakshyapati; Verma, Lokesh

2015-12-01

The antipsychotic properties of haloperidol are primarily attributed to its ability to block dopamine D2 receptors. Histaminergic transmission modulates some of the behavioral effects of haloperidol. Hence, the present study investigated the contribution of central histaminergic transmission in the cataleptic and neuroleptic effect of haloperidol respectively, using bar test and conditioned avoidance response (CAR) in a two-way shuttle box. The studies revealed that haloperidol (0.50 or 1 mg/kg, i.p.) exhibited cataleptic behavior and inhibited conditioned avoidance response (CAR) in the doses 0.25 or 0.50 mg in rats. The rats, pretreated centrally (i.c.v.) with histamine precursor, L-histidine (1, 2.5 μg) or histamine neuronal inducer (H3 receptor antagonist), thioperamide (20, 50 μg/rat), showed an enhanced cataleptic effect with sub-maximal dose of haloperidol (0.5 mg/kg, i.p.). Similarly, the neuroleptic effect of haloperidol (0.25 mg/kg, i.p.) in CAR was also potentiated in the rats pretreated with L-histidine (2.5 μg) or thioperamide (50 μg/rat). Further, the cataleptic effect of haloperidol (1 mg/kg, i.p.) was attenuated in rats pretreated with the H1 receptor antagonist, chlorpheniramine (60, 80 μg/rat, i.c.v.) or H2 receptor antagonist, ranitidine (60 μg/rat, i.c.v.). However, the neuroleptic effect of haloperidol (0.5 mg/kg, i.p.) was completely reversed by pretreatment with ranitidine (60 μg/rat, i.c.v.), and partially attenuated by chlorpheniramine (80 μg/rat, i.c.v.). These findings suggest the possible involvement of histaminergic transmission in the cataleptic and neuroleptic effects of haloperidol probably via H1 or H2 receptor stimulation. Copyright © 2015 Elsevier Inc. All rights reserved.

Brain Targeting of a Water Insoluble Antipsychotic Drug Haloperidol via the Intranasal Route Using PAMAM Dendrimer.

Science.gov (United States)

Katare, Yogesh K; Daya, Ritesh P; Sookram Gray, Christal; Luckham, Roger E; Bhandari, Jayant; Chauhan, Abhay S; Mishra, Ram K

2015-09-08

Delivery of therapeutics to the brain is challenging because many organic molecules have inadequate aqueous solubility and limited bioavailability. We investigated the efficiency of a dendrimer-based formulation of a poorly aqueous soluble drug, haloperidol, in targeting the brain via intranasal and intraperitoneal administration. Aqueous solubility of haloperidol was increased by more than 100-fold in the developed formulation. Formulation was assessed via different routes of administration for behavioral (cataleptic and locomotor) responses, and for haloperidol distribution in plasma and brain tissues. Dendrimer-based formulation showed significantly higher distribution of haloperidol in the brain and plasma compared to a control formulation of haloperidol administered via intraperitoneal injection. Additionally, 6.7 times lower doses of the dendrimer-haloperidol formulation administered via the intranasal route produced behavioral responses that were comparable to those induced by haloperidol formulations administered via intraperitoneal injection. This study demonstrates the potential of dendrimer in improving the delivery of water insoluble drugs to brain.

Use of haloperidol versus atypical antipsychotics and risk of in-hospital death in patients with acute myocardial infarction: cohort study.

Science.gov (United States)

Park, Yoonyoung; Bateman, Brian T; Kim, Dae Hyun; Hernandez-Diaz, Sonia; Patorno, Elisabetta; Glynn, Robert J; Mogun, Helen; Huybrechts, Krista F

2018-03-28

To compare the risk of in-hospital mortality associated with haloperidol compared with atypical antipsychotics in patients admitted to hospital with acute myocardial infarction. Cohort study using a healthcare database. Nationwide sample of patient data from more than 700 hospitals across the United States. 6578 medical patients aged more than 18 years who initiated oral haloperidol or oral atypical antipsychotics (olanzapine, quetiapine, risperidone) during a hospital admission with a primary diagnosis of acute myocardial infarction between 2003 and 2014. In-hospital mortality during seven days of follow-up from treatment initiation. Among 6578 patients (mean age 75.2 years) treated with an oral antipsychotic drug, 1668 (25.4%) initiated haloperidol and 4910 (74.6%) initiated atypical antipsychotics. The mean time from admission to start of treatment (5.3 v 5.6 days) and length of stay (12.5 v 13.6 days) were similar, but the mean treatment duration was shorter in patients using haloperidol compared with those using atypical antipsychotics (2.4 v 3.9 days). 1:1 propensity score matching was used to adjust for confounding. In intention to treat analyses with the matched cohort, the absolute rate of death per 100 person days was 1.7 for haloperidol (129 deaths) and 1.1 for atypical antipsychotics (92 deaths) during seven days of follow-up from treatment initiation. The survival probability was 0.93 in patients using haloperidol and 0.94 in those using atypical antipsychotics at day 7, accounting for the loss of follow-up due to hospital discharge. The unadjusted and adjusted hazard ratios of death were 1.51 (95% confidence interval 1.22 to 1.85) and 1.50 (1.14 to 1.96), respectively. The association was strongest during the first four days of follow-up and decreased over time. By day 5, the increased risk was no longer evident (1.12, 0.79 to 1.59). In the as-treated analyses, the unadjusted and adjusted hazard ratios were 1.90 (1.43 to 2.53) and 1.93 (1.34 to 2

Neurochemical metabolomics reveals disruption to sphingolipid metabolism following chronic haloperidol administration

Science.gov (United States)

McClay, Joseph L.; Vunck, Sarah A.; Batman, Angela M.; Crowley, James J.; Vann, Robert E.; Beardsley, Patrick M.; van den Oord, Edwin J.

2015-01-01

Haloperidol is an effective antipsychotic drug for treatment of schizophrenia, but prolonged use can lead to debilitating side effects. To better understand the effects of long-term administration, we measured global metabolic changes in mouse brain following 3 mg/kg/day haloperidol for 28 days. These conditions lead to movement-related side effects in mice akin to those observed in patients after prolonged use. Brain tissue was collected following microwave tissue fixation to arrest metabolism and extracted metabolites were assessed using both liquid and gas chromatography mass spectrometry (MS). Over 300 unique compounds were identified across MS platforms. Haloperidol was found to be present in all test samples and not in controls, indicating experimental validity. Twenty-one compounds differed significantly between test and control groups at the p haloperidol-treated mice (p = 0.004), a marker previously associated with demyelination. This study further demonstrates the utility of murine neurochemical metabolomics as a method to advance understanding of CNS drug effects. PMID:25850894

Haloperidol for the treatment of nausea and vomiting in palliative care patients.

Science.gov (United States)

Murray-Brown, Fay; Dorman, Saskie

2015-11-02

Nausea and vomiting are common symptoms in patients with terminal, incurable illnesses. Both nausea and vomiting can be distressing. Haloperidol is commonly prescribed to relieve these symptoms. This is an updated version of the original Cochrane review published in Issue 2, 2009, of Haloperidol for the treatment of nausea and vomiting in palliative care patients. To evaluate the efficacy and adverse events associated with the use of haloperidol for the treatment of nausea and vomiting in palliative care patients. For this updated review, we performed updated searches of CENTRAL, EMBASE and MEDLINE in November 2013 and in November 2014. We searched controlled trials registers in March 2015 to identify any ongoing or unpublished trials. We imposed no language restrictions. For the original review, we performed database searching in August 2007, including CENTRAL, MEDLINE, EMBASE, CINAHL and AMED, using relevant search terms and synonyms. Handsearching complemented the electronic searches (using reference lists of included studies, relevant chapters and review articles) for the original review. We considered randomised controlled trials (RCTs) of haloperidol for the treatment of nausea or vomiting, or both, in any setting, for inclusion. The studies had to be conducted with adults receiving palliative care or suffering from an incurable progressive medical condition. We excluded studies where nausea or vomiting, or both, were thought to be secondary to pregnancy or surgery. We imported records from each of the electronic databases into a bibliographic package and merged them into a core database where we inspected titles, keywords and abstracts for relevance. If it was not possible to accept or reject an abstract with certainty, we obtained the full text of the article for further evaluation. The two review authors independently assessed studies in accordance with the inclusion criteria. There were no differences in opinion between the authors with regard to the

Central nervous system effects of haloperidol on THC in healthy male volunteers

NARCIS (Netherlands)

Liem-Moolenaar, Marieke; te Beek, Erik T; de Kam, Marieke L; Franson, Kari L; Kahn, René S; Hijman, Ron; Touw, Daan; van Gerven, Joop M A

2010-01-01

In this study, the hypothesis that haloperidol would lead to an amelioration of Δ9-tetrahydrocannabinol (THC)-induced 'psychotomimetic' effects was investigated. In a double-blind, placebo-controlled, partial three-way crossover ascending dose study the effects of THC, haloperidol and their

Central nervous system effects of haloperidol on THC in healthy male volunteers

NARCIS (Netherlands)

Liem-Moolenaar, Marieke; te Beek, Erik T; de Kam, Marieke L; Franson, Kari L; Kahn, René S; Hijman, Ron; Touw, Daan; van Gerven, Joop M A

In this study, the hypothesis that haloperidol would lead to an amelioration of Δ9-tetrahydrocannabinol (THC)-induced 'psychotomimetic' effects was investigated. In a double-blind, placebo-controlled, partial three-way crossover ascending dose study the effects of THC, haloperidol and their

Metabolic syndrome and drug discontinuation in schizophrenia: a randomized trial comparing aripiprazole olanzapine and haloperidol.

Science.gov (United States)

Parabiaghi, A; Tettamanti, M; D'Avanzo, B; Barbato, A

2016-01-01

To determine whether the prescription of aripiprazole, compared with olanzapine and haloperidol, was associated with a lower frequency of metabolic syndrome (MS) and treatment discontinuation at 1 year. Patients were randomly assigned to be treated open-label and according to usual clinical practice with either aripiprazole, olanzapine, or haloperidol and followed up for 1 year. Three hundred out-patients with persistent schizophrenia were recruited in 35 mental health services. The intention-to-treat (ITT) analysis found no significant differences in the rate of MS between aripiprazole (37%), olanzapine (47%), and haloperidol (42%). Treatment discontinuation for any cause was higher for aripiprazole (52%) than for olanzapine (33%; OR, 0.41; P = 0.004), or haloperidol (37%; OR, 0.51; P = 0.030). No significant difference was found between olanzapine and haloperidol. Time to discontinuation for any cause was longer for olanzapine than for aripiprazole (HR, 0.55; P haloperidol and aripiprazole, or between olanzapine and haloperidol. The prescription of aripiprazole did not significantly reduce the rates of MS, but its treatment retention was worse. Aripiprazole cannot be considered the safest and most effective drug for maintenance treatment of schizophrenia in routine care, although it may have a place in antipsychotic therapy. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

High free thyroxine levels are associated with QTc prolongation in males

NARCIS (Netherlands)

C. van Noord (Charlotte); W.M. van der Deure (Wendy); M.C.J.M. Sturkenboom (Miriam); S.M.J.M. Straus (Sabine); A. Hofman (Albert); T.J. Visser (Theo); J.A. Kors (Jan); J.C.M. Witteman (Jacqueline); B.H.Ch. Stricker (Bruno)

2008-01-01

textabstractThe literature on the effect of excess thyroid hormone on ventricular repolarization is controversial. To study whether free thyroxine (T4) and TSH are associated with QTc prolongation we conducted population-based cohort study. This study was conducted as part of the Rotterdam Study and

Immunohistochemical evidence for the involvement of gonadotropin releasing hormone in neuroleptic and cataleptic effects of haloperidol in mice.

Science.gov (United States)

Fegade, Harshal A; Umathe, Sudhir N

2016-04-01

Blockade of dopamine D2 receptor by haloperidol is attributed for neuroleptic and cataleptic effects; and also for the release of gonadotropin releasing hormone (GnRH) from the hypothalamus. GnRH agonist is reported to exhibit similar behavioural effects as that of haloperidol, and pre-treatment with GnRH antagonist is shown to attenuate the effects of haloperidol, suggesting a possibility that GnRH might mediate the effects of haloperidol. To substantiate such possibility, the influence of haloperidol on GnRH immunoreactivity (GnRH-ir) in the brain was studied in vehicle/antide pre-treated mice by peroxidase-antiperoxidase method. Initially, an earlier reported antide-haloperidol interaction in rat was confirmed in mice, wherein haloperidol (250μg/kg, i.p.) exhibited suppression of conditioned avoidance response (CAR) on two-way shuttle box, and induced catalepsy in bar test; and pre-treatment with antide (50μg/kg, s.c., GnRH antagonist) attenuated both effects of haloperidol. Immunohistochemical study was carried out to identify GnRH-ir in the brain, isolated 1h after haloperidol treatment to mice pre-treated with vehicle/antide. The morphometric analysis of microphotographs of brain sections revealed that haloperidol treatment increased integrated density units of GnRH-ir in various regions of the limbic system. Considering basal GnRH-ir in vehicle treated group as 100%, the increase in GnRH-ir after haloperidol treatment was by 100.98% in the medial septum; 54.26% in the bed nucleus of the stria terminalis; 1152.85% in the anteroventral periventricular nucleus; 120.79% in the preoptic area-organum vasculosum of the lamina terminalis and 138.82% in the arcuate nucleus. Antide did not influence basal and haloperidol induced increase in GnRH-ir in any of the regions. As significant increase in GnRH-ir after haloperidol treatment was observed in such regions of the brain which are reported to directly or indirectly communicate with the hippocampus and basal

Effects of debrisoquin and haloperidol on plasma homovanillic acid concentration in schizophrenic patients.

Science.gov (United States)

Davidson, M; Losonczy, M F; Mohs, R C; Lesser, J C; Powchik, P; Freed, L B; Davis, B M; Mykytyn, V V; Davis, K L

1987-12-01

Plasma levels of the dopamine metabolite homovanillic acid (pHVA) may potentially reflect upon central dopamine activity. This study examines the effects of debrisoquin, haloperidol, and the two drugs combined on pHVA concentrations of schizophrenic patients. Debrisoquin is a drug that suppresses the peripheral formation of homovanillic acid without affecting the central formation. Acute haloperidol administration consistently increased pHVA concentrations in patients pretreated or not pretreated with debrisoquin, suggesting that this increment reflects haloperidol's central and not peripheral effects.

Corrected QT changes during antipsychotic treatment of children and adolescents

DEFF Research Database (Denmark)

Jensen, Karsten Gjessing; Juul, Klaus; Fink-Jensen, Anders

2015-01-01

covering 9 antipsychotics and including 5,423 patients with QTc data (mean age = 12.8 ± 3.6 years, female = 32.1%). Treatments included aripiprazole: studies = 14; n = 814; haloperidol: studies = 1; n = 15; molindone: studies = 3; n = 125; olanzapine: studies = 5; n = 212; paliperidone: studies = 3; n...

Effect of Tribulus terrestris on Haloperidol-induced Catalepsy in Mice

OpenAIRE

Nishchal, B. S.; Rai, S.; Prabhu, M. N.; Ullal, Sheetal D.; Rajeswari, S.; Gopalakrishna, H. N.

2014-01-01

Haloperidol, an antipsychotic drug, leads to the development of a behavioural state called catalepsy, in which the animal is not able to correct an externally imposed posture. In the present study we have attempted to evaluate the anticataleptic effect of Tribulus terrestris on haloperidol-induced catalepsy in albino mice. Mice were allocated to four groups, each group containing six animals. Both, the test drug, Tribulus terrestris and the standard drug trihexyphenidyl were uniformly suspend...

Time dependent effects of haloperidol on glutamine and GABA homeostasis and astrocyte activity in the rat brain

Science.gov (United States)

Konopaske, Glenn T.; Bolo, Nicolas R.; Basu, Alo C.; Renshaw, Perry F.; Coyle, Joseph T.

2013-01-01

Rationale Schizophrenia is a severe, persistent, and fairly common mental illness. Haloperidol is widely used and is effective against the symptoms of psychosis seen in schizophrenia. Chronic oral haloperidol administration decreased the number of astrocytes in the parietal cortex of macaque monkeys (Konopaske et al. Biol Psych, 2008). Since astrocytes play a key role in glutamate metabolism, chronic haloperidol administration was hypothesized to modulate astrocyte metabolic function and glutamate homeostasis. Objectives This study investigated the effects of chronic haloperidol administration on astrocyte metabolic activity and glutamate, glutamine, and GABA homeostasis. Methods We used ex vivo 13C magnetic resonance spectroscopy along with high performance liquid chromatography after [1-13C]glucose and [1,2-13C]acetate administration to analyze forebrain tissue from rats administered oral haloperidol for 1 or 6 months. Results Administration of haloperidol for 1 month produced no changes in 13C labeling of glutamate, glutamine, or GABA, or in their total levels. However, a 6 month haloperidol administration increased 13C labeling of glutamine by [1,2-13C]acetate. Moreover, total GABA levels were also increased. Haloperidol administration also increased the acetate/glucose utilization ratio for glutamine in the 6 month cohort. Conclusions Chronic haloperidol administration in rats appears to increase forebrain GABA production along with astrocyte metabolic activity. Studies exploring these processes in subjects with schizophrenia should take into account the potential confounding effects of antipsychotic medication treatment. PMID:23660600

Further evaluation of the tropane analogs of haloperidol.

Science.gov (United States)

Sampson, Dinithia; Bricker, Barbara; Zhu, Xue Y; Peprah, Kwakye; Lamango, Nazarius S; Setola, Vincent; Roth, Bryan L; Ablordeppey, Seth Y

2014-09-01

Previous work from our labs has indicated that a tropane analog of haloperidol with potent D2 binding but designed to avoid the formation of MPP(+)-like metabolites, such as 4-(4-chlorophenyl)-1-(4-(4-fluorophenyl)-4-oxobutyl)pyridin-1-ium (BCPP(+)) still produced catalepsy, suggesting a strong role for the D2 receptor in the production of catalepsy in rats, and hence EPS in humans. This study tested the hypothesis that further modifications of the tropane analog to produce compounds with less potent binding to the D2 receptor than haloperidol, would produce less catalepsy. These tests have now revealed that while haloperidol produced maximum catalepsy, these compounds produced moderate to low levels of catalepsy. Compound 9, with the least binding affinity to the D2R, produced the least catalepsy and highest Minimum Adverse Effective Dose (MAED) of the analogs tested regardless of their affinities at other receptors including the 5-HT1AR. These observations support the hypothesis that moderation of the D2 binding of the tropane analogs could reduce catalepsy potential in rats and consequently EPS in man. Published by Elsevier Ltd.

Haloperidol response and plasma catecholamines and their metabolites.

Science.gov (United States)

Green, A I; Alam, M Y; Boshes, R A; Waternaux, C; Pappalardo, K M; Fitzgibbon, M E; Tsuang, M T; Schildkraut, J J

1993-06-01

Eleven acutely psychotic patients with schizophrenia or schizoaffective disorder underwent a 5-7 day drug-washout period (with lorazepam allowed) prior to participating in a 6-week controlled dose haloperidol trial. Patients were evaluated longitudinally with clinical ratings and with plasma measures of the catecholamines dopamine (pDA) and norepinephrine (pNE) and their metabolites, homovanillic acid (pHVA) and 3-methoxy-4-hydroxyphenylglycol (pMHPG). All patients exhibited clinical improvement with haloperidol; the decrease in their Brief Psychiatric Rating Scale (BPRS) scores ranged from 32 to 89%. Measures of pHVA increased within the first week of treatment and returned to baseline by week 5. The pattern of change of pDA resembled that of pHVA. The pattern of change of pNE and pMHPG revealed a decrease over the course of treatment. The early increase and the subsequent decrease in pHVA were strongly correlated with improvement in positive symptoms on the BPRS. These data are consistent with previous reports on the change in pHVA and pMHPG during clinical response to haloperidol. The data on change of pDA and pNE further describe the nature of the biochemical response to this drug.

Efficacy of Oral Risperidone, Haloperidol, or Placebo for Symptoms of Delirium Among Patients in Palliative Care: A Randomized Clinical Trial.

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Agar, Meera R; Lawlor, Peter G; Quinn, Stephen; Draper, Brian; Caplan, Gideon A; Rowett, Debra; Sanderson, Christine; Hardy, Janet; Le, Brian; Eckermann, Simon; McCaffrey, Nicola; Devilee, Linda; Fazekas, Belinda; Hill, Mark; Currow, David C

2017-01-01

active arms had more extrapyramidal effects (risperidone, 0.73; 95% CI, 0.09-1.37; P = .03; and haloperidol, 0.79; 95% CI, 0.17-1.41; P = .01). Participants in the placebo group had better overall survival than those receiving haloperidol (hazard ratio, 1.73; 95% CI, 1.20-2.50; P = .003), but this was not significant for placebo vs risperidone (hazard ratio, 1.29; 95% CI, 0.91-1.84; P = .14). In patients receiving palliative care, individualized management of delirium precipitants and supportive strategies result in lower scores and shorter duration of target distressing delirium symptoms than when risperidone or haloperidol are added. anzctr.org.au Identifier: ACTRN12607000562471.

[Comparison of basic carboxypeptidases activity in male rats tissues at a single injection of haloperidol].

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Pravosudova, N A; Bykova, I O

2014-01-01

The influence of a single injection of haloperidol on basic carboxypeptidases (biologically active peptide processing enzymes) activity in rat tissues was studied. Acute exposure to haloperidol increased the activity of carboxypeptidases H (CP H) in hypothalamic-pituitary-adrenal system and cerebellum and reduced such activity in testes. Multidirectional changes of PMSF-inhibited carboxypeptidases activity (PMSF-CP) were observed after a single haloperidol injection in all studied tissues except testes. It is suggested that changes of CP H and PMSF-CP activity might affect levels of regulatory peptides in the brain and blood and thus may be involved in general and side effects of haloperidol on the organism.

Rat brain CYP2D enzymatic metabolism alters acute and chronic haloperidol side-effects by different mechanisms.

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Miksys, Sharon; Wadji, Fariba Baghai; Tolledo, Edgor Cole; Remington, Gary; Nobrega, Jose N; Tyndale, Rachel F

2017-08-01

Risk for side-effects after acute (e.g. parkinsonism) or chronic (e.g. tardive dyskinesia) treatment with antipsychotics, including haloperidol, varies substantially among people. CYP2D can metabolize many antipsychotics and variable brain CYP2D metabolism can influence local drug and metabolite levels sufficiently to alter behavioral responses. Here we investigated a role for brain CYP2D in acutely and chronically administered haloperidol levels and side-effects in a rat model. Rat brain, but not liver, CYP2D activity was irreversibly inhibited with intracerebral propranolol and/or induced by seven days of subcutaneous nicotine pre-treatment. The role of variable brain CYP2D was investigated in rat models of acute (catalepsy) and chronic (vacuous chewing movements, VCMs) haloperidol side-effects. Selective inhibition and induction of brain, but not liver, CYP2D decreased and increased catalepsy after acute haloperidol, respectively. Catalepsy correlated with brain, but not hepatic, CYP2D enzyme activity. Inhibition of brain CYP2D increased VCMs after chronic haloperidol; VCMs correlated with brain, but not hepatic, CYP2D activity, haloperidol levels and lipid peroxidation. Baseline measures, hepatic CYP2D activity and plasma haloperidol levels were unchanged by brain CYP2D manipulations. Variable rat brain CYP2D alters side-effects from acute and chronic haloperidol in opposite directions; catalepsy appears to be enhanced by a brain CYP2D-derived metabolite while the parent haloperidol likely causes VCMs. These data provide novel mechanistic evidence for brain CYP2D altering side-effects of haloperidol and other antipsychotics metabolized by CYP2D, suggesting that variation in human brain CYP2D may be a risk factor for antipsychotic side-effects. Copyright © 2017 Elsevier Inc. All rights reserved.

Dose-response relationship of sertindole and haloperidol using the pharmacopsychometric triangle

DEFF Research Database (Denmark)

Bech, P; Tanghøj, P; Andreasson, K

2011-01-01

Renewed insight into dose-related effects of sertindole and haloperidol was sought by re-analysing published data for antipsychotic effect, extrapyramidal effect, and patient wellbeing - i.e., the important pharmacopsychometric triangle domains.......Renewed insight into dose-related effects of sertindole and haloperidol was sought by re-analysing published data for antipsychotic effect, extrapyramidal effect, and patient wellbeing - i.e., the important pharmacopsychometric triangle domains....

Solution-mediated phase transformation of haloperidol mesylate in the presence of sodium lauryl sulfate.

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Greco, Kristyn; Bogner, Robin

2011-09-01

Forming a salt is a common way to increase the solubility of a poorly soluble compound. However, the solubility enhancement gained by salt formation may be lost due to solution-mediated phase transformation (SMPT) during dissolution. The SMPT of a salt can occur due to a supersaturated solution near the dissolving surface caused by pH or other solution conditions. In addition to changes in pH, surfactants are also known to affect SMPT. In this study, SMPT of a highly soluble salt, haloperidol mesylate, at pH 7 in the presence of a commonly used surfactant, sodium lauryl sulfate (SLS), was investigated. Dissolution experiments were performed using a flow-through dissolution apparatus with solutions containing various concentrations of SLS. Compacts of haloperidol mesylate were observed during dissolution in the flow-through apparatus using a stereomicroscope. Raman microscopy was used to characterize solids. The dissolution of haloperidol mesylate was significantly influenced by the addition of sodium lauryl sulfate. In conditions where SMPT was expected, the addition of SLS at low concentrations (0.1-0.2 mM) reduced the dissolution of haloperidol mesylate. In solutions containing concentrations of SLS above the critical micelle concentration (CMC) (10-15 mM), the dissolution of haloperidol mesylate increased compared to below the CMC. The solids recovered from solubility experiments of haloperidol mesylate indicated that haloperidol free base precipitated at all concentrations of SLS. Above 5 mM of SLS, Raman microscopy suggested a new form, perhaps the estolate salt. The addition of surfactant in solids that undergo solution-mediated phase transformation can add complexity to the dissolution profiles and conversion.

Beneficial effect of candesartan and lisinopril against haloperidol-induced tardive dyskinesia in rat.

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Thakur, Kuldeep Singh; Prakash, Atish; Bisht, Rohit; Bansal, Puneet Kumar

2015-12-01

Tardive dyskinesia is a serious motor disorder of the orofacial region, resulting from chronic neuroleptic treatment of schizophrenia. Candesartan (AT1 antagonist) and lisinopril (ACE inhibitor) has been reported to possess antioxidant and neuroprotective effects. The present study is designed to investigate the effect of candesartan and lisinopril on haloperidol-induced orofacial dyskinesia and oxidative damage in rats. Tardive dyskinesia was induced by administering haloperidol (1 mg/kg i.p.) and concomitantly treated with candesartan (3 and 5 mg/kg p.o.) and lisinopril (10 and 15 mg/kg p.o.) for 3 weeks in male Wistar rats. Various behavioral parameters were assessed on days 0, 7, 14 and 21 and biochemical parameters were estimated at day 22. Chronic administration of haloperidol significantly increased stereotypic behaviors in rats, which were significantly improved by administration of candesartan and lisinopril. Chronic administration of haloperidol significantly increased oxidative stress and neuro-inflammation in the striatum region of the rat's brain. Co-administration of candesartan and lisinopril significantly attenuated the oxidative damage and neuro-inflammation in the haloperidol-treated rat. The present study supports the therapeutic use of candesartan and lisinopril in the treatment of typical antipsychotic-induced orofacial dyskinesia and possible antioxidant and neuro-inflammatory mechanisms. © The Author(s) 2014.

Haloperidol Versus Ondansetron for Treatment of Established Nausea and Vomiting Following General Anesthesia: A Randomized Clinical Trial.

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Yazbeck-Karam, Vanda G; Siddik-Sayyid, Sahar M; Barakat, Hanane B; Korjian, Serge; Aouad, Marie T

2017-02-01

Haloperidol is an antipsychotic. At low doses, it is a useful agent for the prophylaxis of postoperative nausea and vomiting (PONV). However, its use for treating established PONV has not been well studied. This randomized double-blinded trial tested whether haloperidol is noninferior to ondansetron for the early treatment of established PONV in adult patients undergoing general anesthesia. The primary outcome is whether patients were PONV free during the first 4 hours. The noninferiority margin was set at 15%. One hundred twenty patients with PONV received either haloperidol 1 mg intravenously (n = 60) or ondansetron 4 mg intravenously (n = 60). Data from 112 patients (59 in the haloperidol group and 53 in the ondansetron group) were analyzed. Thirty-five patients (52%) in the haloperidol group received 1 or 2 prophylactic antiemetics compared with 42 (79%) in the ondansetron group. Haloperidol was noninferior to ondansetron for the end point of complete response to treatment (defined as the rate of PONV-free patients) for the early (0-4 hour) and the 0- to 24-hour postoperative periods by both the per-protocol and intention-to-treat analyses. In the per-protocol analysis, complete responses in the early period were noted in 35 of 59 patients (59%) and 29 of 53 patients (55%) for the haloperidol and ondansetron groups, respectively (difference 5%; 95% confidence interval [CI]: -13% to 22 %), and in the 0- to 24-hour period in 31 of 59 patients (53%) and 26 of 53 patients (49%) for the haloperidol and ondansetron groups, respectively (difference 4%; 95% CI of the difference: -15% to 21%). In the intention-to-treat analysis, complete responses in the early period were noted in 35 of 60 patients (58%) and 29 of 60 patients (48%) for the haloperidol and ondansetron groups, respectively (difference 10%; 95% CI of difference: -8% to 27%) and in the 0- to 24-hour period in 31 of 60 patients (52%) and 26 of 60 patients (43%) for the haloperidol and ondansetron groups

Nicotine and caffeine modulate haloperidol-induced changes in postsynaptic density transcripts expression: Translational insights in psychosis therapy and treatment resistance.

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de Bartolomeis, Andrea; Iasevoli, Felice; Marmo, Federica; Buonaguro, Elisabetta Filomena; Avvisati, Livia; Latte, Gianmarco; Tomasetti, Carmine

2018-04-01

Caffeine and nicotine are widely used by schizophrenia patients and may worsen psychosis and affect antipsychotic therapies. However, they have also been accounted as augmentation strategies in treatment-resistant schizophrenia. Despite both substances are known to modulate dopamine and glutamate transmission, little is known about the molecular changes induced by these compounds in association to antipsychotics, mostly at the level of the postsynaptic density (PSD), a site of dopamine-glutamate interplay. Here we investigated whether caffeine and nicotine, alone or combined with haloperidol, elicited significant changes in the levels of both transcripts and proteins of the PSD members Homer1 and Arc, which have been implicated in synaptic plasticity, schizophrenia pathophysiology, and antipsychotics molecular action. Homer1a mRNA expression was significantly reduced by caffeine and nicotine, alone or combined with haloperidol, compared to haloperidol. Haloperidol induced significantly higher Arc mRNA levels than both caffeine and caffeine plus haloperidol in the striatum. Arc mRNA expression was significantly higher by nicotine plus haloperidol vs. haloperidol in the cortex, while in striatum gene expression by nicotine was significantly lower than that by both haloperidol and nicotine plus haloperidol. Both Homer1a and Arc protein levels were significantly increased by caffeine, nicotine, and nicotine plus haloperidol. Homer1b mRNA expression was significantly increased by nicotine and nicotine plus haloperidol, while protein levels were unaffected. Locomotor activity was not significantly affected by caffeine, while it was reduced by nicotine. These data indicate that both caffeine and nicotine trigger relevant molecular changes in PSD sites when given in association with haloperidol. Copyright © 2018 Elsevier B.V. and ECNP. All rights reserved.

Event-related potentials reflect impaired temporal interval learning following haloperidol administration.

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Forster, Sarah E; Zirnheld, Patrick; Shekhar, Anantha; Steinhauer, Stuart R; O'Donnell, Brian F; Hetrick, William P

2017-09-01

Signals carried by the mesencephalic dopamine system and conveyed to anterior cingulate cortex are critically implicated in probabilistic reward learning and performance monitoring. A common evaluative mechanism purportedly subserves both functions, giving rise to homologous medial frontal negativities in feedback- and response-locked event-related brain potentials (the feedback-related negativity (FRN) and the error-related negativity (ERN), respectively), reflecting dopamine-dependent prediction error signals to unexpectedly negative events. Consistent with this model, the dopamine receptor antagonist, haloperidol, attenuates the ERN, but effects on FRN have not yet been evaluated. ERN and FRN were recorded during a temporal interval learning task (TILT) following randomized, double-blind administration of haloperidol (3 mg; n = 18), diphenhydramine (an active control for haloperidol; 25 mg; n = 20), or placebo (n = 21) to healthy controls. Centroparietal positivities, the Pe and feedback-locked P300, were also measured and correlations between ERP measures and behavioral indices of learning, overall accuracy, and post-error compensatory behavior were evaluated. We hypothesized that haloperidol would reduce ERN and FRN, but that ERN would uniquely track automatic, error-related performance adjustments, while FRN would be associated with learning and overall accuracy. As predicted, ERN was reduced by haloperidol and in those exhibiting less adaptive post-error performance; however, these effects were limited to ERNs following fast timing errors. In contrast, the FRN was not affected by drug condition, although increased FRN amplitude was associated with improved accuracy. Significant drug effects on centroparietal positivities were also absent. Our results support a functional and neurobiological dissociation between the ERN and FRN.

Haloperidol Selectively Remodels Striatal Indirect Pathway Circuits

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Sebel, Luke E; Graves, Steven M; Chan, C Savio; Surmeier, D James

2017-01-01

Typical antipsychotic drugs are widely thought to alleviate the positive symptoms of schizophrenia by antagonizing dopamine D2 receptors expressed by striatal spiny projection neurons (SPNs). What is less clear is why antipsychotics have a therapeutic latency of weeks. Using a combination of physiological and anatomical approaches in ex vivo brain slices from transgenic mice, it was found that 2 weeks of haloperidol treatment induced both intrinsic and synaptic adaptations specifically within indirect pathway SPNs (iSPNs). Perphenazine treatment had similar effects. Some of these adaptations were homeostatic, including a drop in intrinsic excitability and pruning of excitatory corticostriatal glutamatergic synapses. However, haloperidol treatment also led to strengthening of a subset of excitatory corticostriatal synapses. This slow remodeling of corticostriatal iSPN circuitry is likely to play a role in mediating the delayed therapeutic action of neuroleptics. PMID:27577602

Efficacy and Safety of Levosulpiride Versus Haloperidol Injection in Patients With Acute Psychosis: A Randomized Double-Blind Study.

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Lavania, Sagar; Praharaj, Samir Kumar; Bains, Hariender Singh; Sinha, Vishal; Kumar, Abhinav

2016-01-01

Injectable antipsychotics are frequently required for controlling agitation and aggression in acute psychosis. No study has examined the use of injectable levosulpiride for this indication. To compare the efficacy and safety of injectable levosulpiride and haloperidol in patients with acute psychosis. This was a randomized, double-blind, parallel-group study in which 60 drug-naive patients having acute psychosis were randomly assigned to receive either intramuscular haloperidol (10-20 mg/d) or levosulpiride (25-50 mg/d) for 5 days. All patients were rated on Brief Psychiatric Rating Scale (BPRS), Overt Agitation Severity Scale (OASS), Overt Aggression Scale-Modified (OAS-M) scores, Simpson Angus Scale (SAS), and Barnes Akathisia Rating Scale (BARS). Repeated-measures ANOVA for BPRS scores showed significant effect of time (P haloperidol group as shown by group × time interaction (P = 0.076). Repeated-measures ANOVA for OASS showed significant effect of time (P haloperidol group as shown by group × time interaction (P = 0.032). Lorazepam requirement was much lower in haloperidol group as compared with those receiving levosulpiride (P = 0.022). Higher rates of akathisia and extrapyramidal symptoms were noted in the haloperidol group. Haloperidol was more effective than levosulpiride injection for psychotic symptoms, aggression, and severity of agitation in acute psychosis, but extrapyramidal adverse effects were less frequent with levosulpiride as compared with those receiving haloperidol.

Interactions between estradiol and haloperidol on perseveration and reversal learning in amphetamine-sensitized female rats.

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Almey, Anne; Arena, Lauren; Oliel, Joshua; Shams, Waqqas M; Hafez, Nada; Mancinelli, Cynthia; Henning, Lukas; Tsanev, Aleks; Brake, Wayne G

2017-03-01

There are sex differences associated with schizophrenia, as women exhibit later onset of the disorder, less severe symptomatology, and better response to antipsychotic medications. Estrogens are thought to play a role in these sex differences; estrogens facilitate the effects of antipsychotic medications to reduce the positive symptoms of schizophrenia, but it remains unclear whether estrogens protect against the cognitive symptoms of this disorder. Amphetamine sensitization is used to model some symptoms of schizophrenia in rats, including cognitive deficits like excessive perseveration and slower reversal learning. In this experiment female rats were administered a sensitizing regimen of amphetamine to mimic these cognitive symptoms. They were ovariectomized and administered either low or high estradiol replacement as well as chronic administration of the antipsychotic haloperidol, and were assessed in tests of perseveration and reversal learning. Results of these experiments demonstrated that, in amphetamine-sensitized rats, estradiol alone does not affect perseveration or reversal learning. However, low estradiol facilitates a 0.25mg/day dose of haloperidol to reduce perseveration and improve reversal learning. Combined high estradiol and 0.25mg/day haloperidol has no effect on perseveration or reversal learning, but high estradiol facilitates the effects of 0.13mg/day haloperidol to reduce perseveration and improve reversal learning. Thus, in amphetamine-sensitized female rats, 0.25mg/day haloperidol only improved perseveration and reversal learning when estradiol was low, while 0.13mg/day haloperidol only improved these cognitive processes when estradiol was high. These findings suggest that estradiol facilitates the effects of haloperidol to improve perseveration and reversal learning in a dose-dependent manner. Copyright © 2017 Elsevier Inc. All rights reserved.

Analysis of the potential effect of ponatinib on the QTc interval in patients with refractory hematological malignancies.

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Sonnichsen, Daryl; Dorer, David J; Cortes, Jorge; Talpaz, Moshe; Deininger, Michael W; Shah, Neil P; Kantarjian, Hagop M; Bixby, Dale; Mauro, Michael J; Flinn, Ian W; Litwin, Jeffrey; Turner, Christopher D; Haluska, Frank G

2013-06-01

Cardiac dysfunction, particularly QT interval prolongation, has been observed with tyrosine kinase inhibitors approved to treat chronic myeloid leukemia. This study examines the effects of ponatinib on cardiac repolarization in patients with refractory hematological malignancies enrolled in a phase 1 trial. Electrocardiograms (ECGs) were collected at 3 dose levels (30, 45, and 60 mg) at 6 time points. Electrocardiographic parameters, including QTc interval, were measured, and 11 morphological analyses were conducted. Central tendency analyses of ECG parameters were performed using time-point and time-averaged approaches. All patients with at least 2 baseline ECGs and 1 on-treatment ECG were included in the analyses. Patients with paired ECGs and plasma samples were included in the pharmacokinetic/pharmacodynamic analysis to examine the relationship between ponatinib plasma concentration and change from baseline in QT intervals. Thirty-nine patients at the 30-, 45-, and 60-mg dose levels were included in the central tendency and morphological analyses. There was no significant effect on cardiac repolarization, as evidenced by non-clinically significant mean QTcF changes from baseline of -10.9, -3.6, and -5.0 ms for the 30-, 45-, and 60-mg dose levels, respectively. The morphological analysis revealed 2 patients with atrial fibrillation and 2 with T wave inversion. Seventy-five patients were included in the pharmacokinetic/pharmacodynamic analysis across all dose levels. The slope of the relationship for QTcF versus plasma ponatinib concentration was not positive (-0.0171), indicating no exposure-effect relationship. Ponatinib is associated with a low risk of QTc prolongation in patients with refractory hematological malignancies.

Unexplained Graft Dysfunction after Heart Transplantation—Role of Novel Molecular Expression Test Score and QTc-Interval: A Case Report

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Khurram Shahzad

2010-01-01

Full Text Available In the current era of immunosuppressive medications there is increased observed incidence of graft dysfunction in the absence of known histological criteria of rejection after heart transplantation. A noninvasive molecular expression diagnostic test was developed and validated to rule out histological acute cellular rejection. In this paper we present for the first time, longitudinal pattern of changes in this novel diagnostic test score along with QTc-interval in a patient who was admitted with unexplained graft dysfunction. Patient presented with graft failure with negative findings on all known criteria of rejection including acute cellular rejection, antibody mediated rejection and cardiac allograft vasculopathy. The molecular expression test score showed gradual increase and QTc-interval showed gradual prolongation with the gradual decline in graft function. This paper exemplifies that in patients presenting with unexplained graft dysfunction, GEP test score and QTc-interval correlate with the changes in the graft function.

Haloperidol for delirium in critically ill patients - protocol for a systematic review

DEFF Research Database (Denmark)

Barbateskovic, M; Kraus, S R; Collet, M O

2018-01-01

, relatives, and societies is considerable. The objective of this systematic review was to critically access the evidence of randomised clinical trials on the effects of haloperidol vs. placebo or any other agents for delirium in critically ill patients. METHODS: We will search for randomised clinical trials...... decision makers on the use of or future trials with haloperidol for the management of delirium in critically ill patients....

Psychopharmacological correlates of post-psychotic depression: a double-blind investigation of haloperidol vs thiothixene in outpatient schizophrenia.

Science.gov (United States)

Abuzzahab, F S; Zimmerman, R L

1982-03-01

A 24-week double-blind study was conducted to compare haloperidol and thiothixene for efficacy and safety in 46 schizophrenic outpatients. In addition to the standard psychiatric rating scales, Brief Psychiatric Rating Scale (BPRS), Nurses' Observation Scale for Inpatient Evaluation (NOSIE), and Evaluation of Social Functioning Rating (ESFR), two scales more sensitive to the incidence of treatment emergent depression were utilized. They were the Hamilton Depression Scale (HPRSD) and the Zung Self-rating Depression Scale (ZUNG). On the BPRS factors, haloperidol was significantly superior to thiothixene in Thought Disturbance and Hostility-Suspiciousness, and in Total symptomatology. Haloperidol was also significantly superior to thiothixene in Cognitive Disturbance on the HPRSD. Results of global evaluations suggested haloperidol produced slightly more rapid relief of symptoms than did thiothixene. The inclusion of the depression scales was useful in following patients who exhibited depressive symptoms; clinically significant depression was seen in 5 patients receiving haloperidol and 3 receiving thiothixene. A high incidence of akathisia in the thiothixene group was responsible for a statistically significant difference between groups in the number of central nervous system symptoms. Mean doses of test drugs were 17.5 mg/day for haloperidol an 31.8 mg/day for thiothixene. The study showed that haloperidol was equal to and in some parameters superior to thiothixene in producing improvement in the symptoms of psychosis.

Haloperidol Suppresses NF-kappaB to Inhibit Lipopolysaccharide-Induced Pro-Inflammatory Response in RAW 264 Cells.

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Yamamoto, Shunsuke; Ohta, Noriyuki; Matsumoto, Atsuhiro; Horiguchi, Yu; Koide, Moe; Fujino, Yuji

2016-02-04

BACKGROUND Haloperidol, a tranquilizing agent, is administered both to treat symptoms of psychotic disorders and to sedate agitated and delirious patients. Notably, haloperidol has been suggested to inhibit the immune response through unknown mechanisms. We hypothesized that the sedative modulates the immune response via NF-κB. MATERIAL AND METHODS Using flow cytometry, we analyzed the effects of haloperidol on expression CD80 and CD86 in RAW 264 cells and in primary macrophages derived from bone marrow. Secretion of interleukin (IL)-1β, IL-6, and IL-12 p40 was measured by enzyme-linked immunosorbent assay. In addition, NF-κB activation was evaluated using a reporter assay based on secretory embryonic alkaline phosphatase. Finally, synthetic antagonists were used to identify the dopamine receptor that mediates the effects of haloperidol. RESULTS Haloperidol inhibited NF-κB activation, and thereby suppressed expression of CD80, as well as secretion of IL-1β, IL-6, and IL-12 p40. CD80 and IL-6 levels were similarly attenuated by a D2-like receptor antagonist, but not by a D1-like receptor antagonist. CONCLUSIONS The data strongly suggest that haloperidol inhibits the immune response by suppressing NF-kB signaling via the dopamine D2 receptor.

QT Interval Prolongation Associated with Intramuscular Ziprasidone in Chinese Patients: A Case Report and a Comprehensive Literature Review with Meta-Analysis

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Xian-Bin Li

2014-01-01

Full Text Available Intramuscular (IM ziprasidone has been associated with QTc interval prolongations in patients with preexisting risk factors. A 23-year-old male Chinese schizophrenia patient experienced an increase of QTc interval of 83 milliseconds (ms after receiving 20 mg IM ziprasidone (baseline and increased QT/QTc were, respectively, 384/418 and 450/501. This was rated as a probable adverse drug reaction (ADR by the Liverpool ADR causality assessment tool. A systematic review including all types of trials reporting the effect of IM ziprasidone on the QTc interval prolongation identified 19 trials with a total of 1428 patients. Mean QTc change from baseline to end of each study was −3.7 to 12.8 ms after IM ziprasidone. Four randomized trials (3 of 4 published in Chinese were used to calculate a meta-analysis of QTc interval prolongation which showed no significant differences between IM ziprasidone and IM haloperidol groups (risk ratio 0.49 to 4.31, 95% confidence interval 0.09 to 19.68, P = 0.06 to 0.41. However, our review included two cases of patients who experienced symptoms probably related to QTc prolongation after IM ziprasidone. Thus, careful screening and close monitoring, including baseline ECG, should be considered in patients receiving IM ziprasidone for the first time.

Haloperidol Abrogates Matrix Metalloproteinase-9 Expression by Inhibition of NF-κB Activation in Stimulated Human Monocytic Cells

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Yueh-Lun Lee

2018-01-01

Full Text Available Much evidence has indicated that matrix metalloproteinases (MMPs participate in the progression of neuroinflammatory disorders. The present study was undertaken to investigate the inhibitory effect and mechanism of the antipsychotic haloperidol on MMP activation in the stimulated THP-1 monocytic cells. Haloperidol exerted a strong inhibition on tumor necrosis factor- (TNF- α-induced MMP-9 gelatinolysis of THP-1 cells. A concentration-dependent inhibitory effect of haloperidol was observed in TNF-α-induced protein and mRNA expression of MMP-9. On the other hand, haloperidol slightly affected cell viability and tissue inhibition of metalloproteinase-1 levels. It significantly inhibited the degradation of inhibitor-κB-α (IκBα in activated cells. Moreover, it suppressed activated nuclear factor-κB (NF-κB detected by a mobility shift assay, NF-κB reporter gene, and chromatin immunoprecipitation analyses. Consistent with NF-κB inhibition, haloperidol exerted a strong inhibition of lipopolysaccharide- (LPS- induced MMP-9 gelatinolysis but not of transforming growth factor-β1-induced MMP-2. In in vivo studies, administration of haloperidol significantly attenuated LPS-induced intracerebral MMP-9 activation of the brain homogenate and the in situ in C57BL/6 mice. In conclusion, the selective anti-MMP-9 activation of haloperidol could possibly involve the inhibition of the NF-κB signal pathway. Hence, it was found that haloperidol treatment may represent a bystander of anti-MMP actions for its conventional psychotherapy.

Neuroleptic binding sites: specific labeling in mice with [18F]haloperidol, a potential tracer for positron emission tomography

International Nuclear Information System (INIS)

Zanzonico, P.B.; Bigler, R.E.; Schmall, B.

1983-01-01

Haloperidol labeled with fluorine- 18 (T 1/2 . 110 min, positron emission 97%), prepared yielding .04 Ci/millimole by the Balz-Schiemann reaction, was evaluated in a murine model as a potential radiotracer for noninvasive determination, by positron-emission tomography, of regional concentrations of brain dopamine receptors in patients. As the haloperidol dose in mice was increased from 0.01 to 1000 micrograms/kg, the relative concentration of [ 18 F]haloperidol (microCi per g specimen/microCi per g of body mass), at one hour after injection decreased from 30 to 1.0 in the striatum and from 8.0 to 1.0 in the cerebellum. The striatal radioactivity, plotted as relative concentration against log of dose, decreased sigmoidally, presumably reflecting competition between labeled and unlabeled haloperidol for a single class of accessible binding sites. Because the cerebellum is relatively deficient in dopamine receptors, the observed decrease in cerebellar radioactivity may reflect a saturable component of haloperidol transport into brain. The high brain concentrations and the unexpectedly high striatum-to-cerebellum concentration ratios (greater than 4 at haloperidol doses less than or equal to 1 microgram/kg) suggest that [ 18 F]haloperidol warrants further investigation as a potential radiotracer for dopamine receptors

Ferrocene, ruthenocene or rhodocene analogues of Haloperidol. Synthesis and organ distribution after labelling with 103Ru or 103mRh

International Nuclear Information System (INIS)

Wenzel, M.; Wu, Y.

1988-01-01

Ferrocene-Haloperidol was synthesized by N-alkylation of 4-(4'-chlorophenyl)-4-hydroxypiperidine with 1-ferrocenyl-4-chlor-butan-1-on. By heating the ferrocene-haloperidol with 103 RuCl 3 the 103 Ru-labelled ruthenocene-haloperidol was obtained. This compound showed a high affinity for lung but not for brain in rats and mice. The decay of the 103 Ru labelled compound results in the formation of the 103m Rh labelled rhodocene-haloperidol, which is rapidly oxidized by air to the corresponding rhodocinium-haloperidol. This compound can be separated by extraction and TLC. (author)

The Power of Phase I Studies to Detect Clinical Relevant QTc Prolongation: A Resampling Simulation Study

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Georg Ferber

2015-01-01

Full Text Available Concentration-effect (CE models applied to early clinical QT data from healthy subjects are described in the latest E14 Q&A document as promising analysis to characterise QTc prolongation. The challenges faced if one attempts to replace a TQT study by thorough ECG assessments in Phase I based on CE models are the assurance to obtain sufficient power and the establishment of a substitute for the positive control to show assay sensitivity providing protection against false negatives. To demonstrate that CE models in small studies can reliably predict the absence of an effect on QTc, we investigated the role of some key design features in the power of the analysis. Specifically, the form of the CE model, inclusion of subjects on placebo, and sparse sampling on the performance and power of this analysis were investigated. In this study, the simulations conducted by subsampling subjects from 3 different TQT studies showed that CE model with a treatment effect can be used to exclude small QTc effects. The number of placebo subjects was also shown to increase the power to detect an inactive drug preventing false positives while an effect can be underestimated if time points around tmax are missed.

Effects of d-Amphetamine and Haloperidol on Modulation of the Human Acoustic Startle Response

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Hossein Kaviani

2006-04-01

Full Text Available "nObjective:This study aimed to examine the effects of haloperidol and amphetamine on human startle response modulated by emotionally-toned film clips. "n "n Method:Sixty participants, in two groups (one receiving haloperidol and the other receiving amphetamine were tested using electromyography (EMG to measure eye-blink muscle (orbicular oculi while different emotions were induced by six 2-minute film clips. Results:An affective rating shows the negative and positive effects of the two drugs on emotional reactivity, neither amphetamine nor haloperidol had any impact on the modulation of the startle response. Conclusion: The methodological and theoretical aspects of the study and findings will be discussed.

Effects of Antipsychotic Drugs Haloperidol and Clozapine on Visual Responses of Retinal Ganglion Cells in a Rat Model of Retinitis Pigmentosa.

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Jensen, Ralph J

2016-12-01

In the P23H rat model of retinitis pigmentosa, the dopamine D2 receptor antagonists sulpiride and eticlopride appear to improve visual responses of retinal ganglion cells (RGCs) by increasing light sensitivity of RGCs and transforming abnormal, long-latency ON-center RGCs into OFF-center cells. Antipsychotic drugs are believed to mediate their therapeutic benefits by blocking D2 receptors. This investigation was conducted to test whether haloperidol (a typical antipsychotic drug) and clozapine (an atypical antipsychotic drug) could similarly alter the light responses of RGCs in the P23H rat retina. Extracellular recordings were made from RGCs in isolated P23H rat retinas. Responses of RGCs to flashes of light were evaluated before and during bath application of a drug. Both haloperidol and clozapine increased light sensitivity of RGCs on average by ∼0.3 log unit. For those ON-center RGCs that exhibit an abnormally long-latency response to the onset of a small spot of light, both haloperidol and clozapine brought out a short-latency OFF response and markedly reduced the long-latency ON response. The selective serotonin 5-HT2A antagonist MDL 100907 had similar effects on RGCs. The effects of haloperidol on light responses of RGCs can be explained by its D2 receptor antagonism. The effects of clozapine on light responses of RGCs on the other hand may largely be due to its 5-HT2A receptor antagonism. Overall, the results suggest that antipsychotic drugs may be useful in improving vision in patients with retinitis pigmentosa.

The influence of chronic exposure to antipsychotic medications on brain size before and after tissue fixation: a comparison of haloperidol and olanzapine in macaque monkeys

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Dorph-Petersen, Karl-Anton; Pierri, Joseph N; Perel, James M

2005-01-01

exposed to oral haloperidol, olanzapine or sham for a 17-27 month period. The resulting plasma drug levels were comparable to those seen in subjects with schizophrenia treated with these medications. After the exposure, we observed an 8-11% reduction in mean fresh brain weights as well as left cerebrum...

Prevalence and risk factors related to haloperidol use for delirium in adult intensive care patients

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Collet, Marie O; Caballero, Jesús; Sonneville, Romain

2018-01-01

PURPOSE: We assessed the prevalence and variables associated with haloperidol use for delirium in ICU patients and explored any associations of haloperidol use with 90-day mortality. METHODS: All acutely admitted, adult ICU patients were screened during a 2-week inception period. We followed...... the patient throughout their ICU stay and assessed 90-day mortality. We assessed patients and their variables in the first 24 and 72 h in ICU and studied their association together with that of ICU characteristics with haloperidol use. RESULTS: We included 1260 patients from 99 ICUs in 13 countries. Delirium...... occurred in 314/1260 patients [25% (95% confidence interval 23-27)] of whom 145 received haloperidol [46% (41-52)]. Other interventions for delirium were benzodiazepines in 36% (31-42), dexmedetomidine in 21% (17-26), quetiapine in 19% (14-23) and olanzapine in 9% (6-12) of the patients with delirium...

Activation of the sigma-1 receptor by haloperidol metabolites facilitates brain-derived neurotrophic factor secretion from human astroglia.

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Dalwadi, Dhwanil A; Kim, Seongcheol; Schetz, John A

2017-05-01

Glial cells play a critical role in neuronal support which includes the production and release of the neurotrophin brain-derived neurotrophic factor (BDNF). Activation of the sigma-1 receptor (S1R) has been shown to attenuate inflammatory stress-mediated brain injuries, and there is emerging evidence that this may involve a BDNF-dependent mechanism. In this report we studied S1R-mediated BDNF release from human astrocytic glial cells. Astrocytes express the S1R, which mediates BDNF release when stimulated with the prototypical S1R agonists 4-PPBP and (+)-SKF10047. This effect could be antagonized by a selective concentration of the S1R antagonist BD1063. Haloperidol is known to have high affinity interactions with the S1R, yet it was unable to facilitate BDNF release. Remarkably, however, two metabolites of haloperidol, haloperidol I and haloperidol II (reduced haloperidol), were discovered to facilitate BDNF secretion and this effect was antagonized by BD1063. Neither 4-PPBP, nor either of the haloperidol metabolites affected the level of BDNF mRNA as assessed by qPCR. These results demonstrate for the first time that haloperidol metabolites I and II facilitate the secretion of BDNF from astrocytes by acting as functionally selective S1R agonists. Copyright © 2017 Elsevier Ltd. All rights reserved.

Report: Protective effects of rice bran oil in haloperidol-induced tardive dyskinesia and serotonergic responses in rats.

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Samad, Noreen; Haleem, Muhammad Abdul; Haleem, Darakhshan Jabeen

2016-07-01

Effect of administration of Rice bran oil (RBO) was evaluated on haloperidol elicited tardive dyskinesia in rats. Albino Wistar rats treated with haloperidol in drinking water at a dose of 0.2mg/kg/day and RBO by oral tubes at a dose of 0.4 mL/day for 5 weeks. Motor coordination, VCMs and 8-hydroxy-2-(di-n-propylamino) tetraline)[8-OH-DPAT] _syndrome were monitored. Striatal serotonin (5-hydroxytryptamine; 5-HT) and 5-hydroxyindolacetic acid (5-HIAA) levels were determined by high performance liquid chromatography (HPLC-EC). Rats treated with haloperidol orally at a dose of for a period of 5 weeks developed VCMs, which increased progressively as the treatment continued for 5 weeks. Motor coordination impairment started after the 1st week and was maximally impaired after 3 weeks and gradually returned to the 1st week value. Co-administration of RBO prevented haloperidol_induced VCMs as well impairment of motor coordination. The intensity of 8-OH-DPAT_induced syndrome and decreased 5-HT metabolism were greater in water + haloperidol treated animals than RBO + haloperidol treated animals. The present study suggested that involvement of free radical in the development of TD and point to RBO as a possible therapeutic option to treat this hyperkinetic motor disorder.

Long-Term Haloperidol Treatment Prolongs QT Interval and Increases Expression of Sigma 1 and IP3 Receptors in Guinea Pig Hearts.

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Stracina, Tibor; Slaninova, Iva; Polanska, Hana; Axmanova, Martina; Olejnickova, Veronika; Konecny, Petr; Masarik, Michal; Krizanova, Olga; Novakova, Marie

2015-07-01

Haloperidol is a neuroleptic drug used for a medication of various psychoses and deliria. Its administration is frequently accompanied by cardiovascular side effects, expressed as QT interval prolongation and occurrence of even lethal arrhythmias. Despite these side effects, haloperidol is still prescribed in Europe in clinical practice. Haloperidol binds to sigma receptors that are coupled with inositol 1,4,5-trisphosphate (IP3) receptors. Sigma receptors are expressed in various tissues, including heart muscle, and they modulate potassium channels. Together with IP3 receptors, sigma receptors are also involved in calcium handling in various tissues. Therefore, the present work aimed to study the effects of long-term haloperidol administration on the cardiac function. Haloperidol (2 mg/kg once a day) or vehiculum was administered by intraperitoneal injection to guinea pigs for 21 consecutive days. We measured the responsiveness of the hearts isolated from the haloperidol-treated animals to additional application of haloperidol. Expression of the sigma 1 receptor and IP3 receptors was studied by real time-PCR and immunohistochemical analyses. Haloperidol treatment caused the significant decrease in the relative heart rate and the prolongation of QT interval of the isolated hearts from the haloperidol-treated animals, compared to the hearts isolated from control animals. The expression of sigma 1 and IP3 type 1 and type 2 receptors was increased in both atria of the haloperidol-treated animals but not in ventricles. The modulation of sigma 1 and IP3 receptors may lead to altered calcium handling in cardiomyocytes and thus contribute to changed sensitivity of cardiac cells to arrhythmias.

First-Generation Antipsychotic Haloperidol Alters the Functionality of the Late Endosomal/Lysosomal Compartment in Vitro.

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Canfrán-Duque, Alberto; Barrio, Luis C; Lerma, Milagros; de la Peña, Gema; Serna, Jorge; Pastor, Oscar; Lasunción, Miguel A; Busto, Rebeca

2016-03-18

First- and second-generation antipsychotics (FGAs and SGAs, respectively), have the ability to inhibit cholesterol biosynthesis and also to interrupt the intracellular cholesterol trafficking, interfering with low-density lipoprotein (LDL)-derived cholesterol egress from late endosomes/lysosomes. In the present work, we examined the effects of FGA haloperidol on the functionality of late endosomes/lysosomes in vitro. In HepG2 hepatocarcinoma cells incubated in the presence of 1,1'-dioctadecyl-3,3,3,3'-tetramethylindocarbocyanineperchlorate (DiI)-LDL, treatment with haloperidol caused the enlargement of organelles positive for late endosome markers lysosome-associated membrane protein 2 (LAMP-2) and LBPA (lysobisphosphatidic acid), which also showed increased content of both free-cholesterol and DiI derived from LDL. This indicates the accumulation of LDL-lipids in the late endosomal/lysosomal compartment caused by haloperidol. In contrast, LDL traffic through early endosomes and the Golgi apparatus appeared to be unaffected by the antipsychotic as the distribution of both early endosome antigen 1 (EEA1) and coatomer subunit β (β-COP) were not perturbed. Notably, treatment with haloperidol significantly increased the lysosomal pH and decreased the activities of lysosomal protease and β-d-galactosidase in a dose-dependent manner. We conclude that the alkalinization of the lysosomes' internal milieu induced by haloperidol affects lysosomal functionality.

Haloperidol and sudden cardiac death in dementia: autopsy findings in psychiatric inpatients.

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Ifteni, Petru; Grudnikoff, Eugene; Koppel, Jeremy; Kremen, Neil; Correll, Christoph U; Kane, John M; Manu, Peter

2015-12-01

Treatment with haloperidol has been shown, in studies using death certificates and prescription files, to be associated with an excess of sudden cardiac deaths, and regulatory warnings highlight this risk in patients with dementia. We used autopsy findings to determine whether the rate of sudden cardiac death is greater in cases of unexpected deaths of patients with dementia treated with haloperidol. From 1989 through 2013, 1219 patients with a primary diagnosis of dementia with behavioral disturbance were admitted to a psychiatric hospital, and 65 (5.3%) died suddenly. Sixty-five patients (5.3%) died unexpectedly. Complete post-mortem examinations after the sudden death were performed in 55 (84.6%) patients. Twenty-seven of the autopsied cases (49.1%) had been treated with haloperidol orally (2.2 mg ± 2.1 mg/day), the only antipsychotic used in this cohort. Univariable comparisons and multivariable regression analyses compared the groups of patients with or without sudden cardiac death. The leading causes of death were sudden cardiac death (32.7%), myocardial infarction (25.5% of patients), pneumonia (23.6%), and stroke (10.9%). Patients with sudden cardiac death and those with anatomically established cause of death were similar regarding the use of haloperidol (p = 0.5). Sudden cardiac death patients were more likely to suffer from Alzheimer's dementia (p = 0.027) and to have a past history of heart disease (p = 0.0094), and less likely to have been treated with a mood stabilizer (p = 0.024), but none of these variables were independent predictors of sudden cardiac death. Autopsy data suggest that oral haloperidol is not associated with increased risk of sudden cardiac death in psychiatric inpatients with dementia. Copyright © 2015 John Wiley & Sons, Ltd.

Movement disorders induced in monkeys by chronic haloperidol treatment

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Weiss, B; Santelli, S; Lusink, G

1977-01-01

After several months of treatment, Cebus apella, Cebus albifrons, and Saimiri sciurea monkeys maintained on haloperidol, in doses of 0.5 or 1.0 mg/kg orally 5 days per week, began to display severe movement disorders, typically 1 to 6 h post-drug. Cebus monkeys exhibited violent, uncontrolled movements that flung the animals about the cage. Such episodes usually lasted only a few minutes, recurring several times during the period following drug ingestion. Writhing and bizarre postures dominated the response in S. sciurea. Cessation of drug treatment produced no distinctive after-effects. When tested as long as 508 days after the last administration, however, Cebus monkeys responded to haloperidol with several episodes of hyperkinesis, even at challenge doses considerably lower than those in the original treatment.

In-hospital cardiac arrest is associated with use of non-antiarrhythmic QTc-prolonging drugs

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De Bruin, Marie L; Langendijk, Pim N J; Koopmans, Richard P

2007-01-01

a case-control study in which patients, for whom intervention of the advanced life support resuscitation team was requested for cardiac arrest between 1995 and 2003 in the Academic Medical Centre, Amsterdam, were compared with controls regarding current use of non-antiarrhythmic QTc-prolonging drugs...

Quetiapine versus haloperidol in the treatment of delirium: a double-blind, randomized, controlled trial

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Maneeton B

2013-07-01

Full Text Available Benchalak Maneeton,1 Narong Maneeton,1 Manit Srisurapanont,1 Kaweesak Chittawatanarat2 1Department of Psychiatry, 2Department of Surgery, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand Background: Atypical antipsychotic drugs may have low propensity to induce extrapyramidal side effects in delirious patients. This study aimed to compare the efficacy and tolerability between quetiapine and haloperidol in controlling delirious behavior. Methods: A 7-day prospective, double-blind, randomized controlled trial was conducted from June 2009 to April 2011 in medically ill patients with delirium. Measures used for daily assessment included the Delirium Rating Scale-revised-98 (DRS-R-98 and total sleep time. The Clinical Global Impression, Improvement (CGI–I and the Modified (nine-item Simpson–Angus Scale were applied daily. The primary outcome was the DRS-R-98 severity scores. The data were analyzed on an intention-to-treat basis. Results: Fifty-two subjects (35 males and 17 females were randomized to receive 25–100 mg/day of quetiapine (n = 24 or 0.5–2.0 mg/day of haloperidol (n = 28. Mean (standard deviation doses of quetiapine and haloperidol were 67.6 (9.7 and 0.8 (0.3 mg/day, respectively. Over the trial period, means (standard deviation of the DRS-R-98 severity scores were not significantly different between the quetiapine and haloperidol groups (-22.9 [6.9] versus -21.7 [6.7]; P = 0.59. The DRS-R-98 noncognitive and cognitive subscale scores were not significantly different. At end point, the response and remission rates, the total sleep time, and the Modified (nine-item Simpson–Angus scores were also not significantly different between groups. Hypersomnia was common in the quetiapine-treated patients (33.3%, but not significantly higher than that in the haloperidol-treated group (21.4%. Limitations: Patients were excluded if they were not able to take oral medications, and the sample size was small. Conclusion: Low

Changes caused by haloperidol are blocked by music in Wistar rat.

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Tasset, Inmaculada; Quero, Ismael; García-Mayórgaz, Ángel D; del Río, Manuel Causse; Túnez, Isaac; Montilla, Pedro

2012-06-01

This study sought to evaluate the effect of classical music, using Mozart's sonata for two pianos (K. 448), on changes in dopamine (DA) levels in the striatal nucleus (SN), prefrontal cortex (PFC) and mesencephalon, and on prolactin (PRL) and corticosterone secretion in adult male Wistar rats. Rats were divided into four groups: (1) control, (2) haloperidol treatment (single dose of 2 mg/kg s.c.), (3) music (two 2-h sessions per day) and (4) haloperidol plus music. Rats were sacrificed 2 h after haloperidol injection. Music prompted a fall in plasma PRL and corticosterone levels in healthy rats (P music was associated with a significant increase in DA levels in all groups, with the increase being particularly marked in PFC and SN (P music, by contrast, enhances DA activity and turnover in the brain. The results obtained here bear out reports that music triggers a reduction in systolic pressure and an increase in mesencephalon dopamine levels in human and rats treated with ecstasy, through a calmodulin-dependent system.

Evolution of plasma homovanillic acid (HVA) in chronic schizophrenic patients treated with haloperidol.

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Galinowski, A; Poirier, M F; Aymard, N; Leyris, A; Beauverie, P; Bourdel, M C; Loo, H

1998-06-01

In a 4-week study of 14 drug-free schizophrenic patients (according to DSM-III-R), free and conjugated fractions of plasma homovanillic acid (pHVA) were repeatedly measured. Free HVA levels decreased during the first 2 h of haloperidol intake (P pHVA may be a better reflection of the action of haloperidol than free pHVA levels and it may be of prognostic value in terms of drug response.

Carnitine congener mildronate protects against stress- and haloperidol-induced impairment in memory and brain protein expression in rats.

Science.gov (United States)

Beitnere, Ulrika; Dzirkale, Zane; Isajevs, Sergejs; Rumaks, Juris; Svirskis, Simons; Klusa, Vija

2014-12-15

The present study investigates the efficacy of mildronate, a carnitine congener, to protect stress and haloperidol-induced impairment of memory in rats and the expression of brain protein biomarkers involved in synaptic plasticity, such as brain-derived neurotrophic factor (BDNF), acetylcholine esterase and glutamate decarboxylase 67 (GAD67). Two amnesia models were used: 2h immobilization stress and 3-week haloperidol treatment. Stress caused memory impairment in the passive avoidance test and induced a significant 2-fold BDNF elevation in hippocampal and striatal tissues that was completely inhibited by mildronate. Mildronate decreased the level of GAD67 (but not acetylcholine esterase) expression by stress. Haloperidol decrease by a third hippocampal BDNF and acetylcholine esterase (but not GAD67) expression, which was normalized by mildronate; it also reversed the haloperidol-induced memory impairment in Barnes test. The results suggest the usefulness of mildronate as protector against neuronal disturbances caused by stress or haloperidol. Copyright © 2014 Elsevier B.V. All rights reserved.

Antagonism by supidimide of haloperidol-induced augmentation of [3H]-spiperone binding in rat striatum

International Nuclear Information System (INIS)

Hennies, H.H.; Hess, V.; Flohe, L.

1984-01-01

Rats were treated for two weeks with haloperidol alone or with additional test drugs and the D 2 receptor density in the striatum was investigated after a drug-free period of five days. The D 2 receptor system as analysed by [ 3 H]-spinerone binding was best characterized by a model with two binding sites of different affinity. Chronic haloperidol treatment substantially augmented the total binding capacity 2-(2-Oxo-3-piperidyl)-1,2-benzisothiazoline-3-one-1,1-dioxide (supidimide), a functional synergist of neuroleptics in acute experiments, surprisingly antagonized the haloperidol-induced receptor augmentation, whereas other CNS depressants (diazepam and phenobarbital) were ineffective. (orig./MG) [de

Neurochemical Metabolomics Reveals Disruption to Sphingolipid Metabolism Following Chronic Haloperidol Administration.

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McClay, Joseph L; Vunck, Sarah A; Batman, Angela M; Crowley, James J; Vann, Robert E; Beardsley, Patrick M; van den Oord, Edwin J

2015-09-01

Haloperidol is an effective antipsychotic drug for treatment of schizophrenia, but prolonged use can lead to debilitating side effects. To better understand the effects of long-term administration, we measured global metabolic changes in mouse brain following 3 mg/kg/day haloperidol for 28 days. These conditions lead to movement-related side effects in mice akin to those observed in patients after prolonged use. Brain tissue was collected following microwave tissue fixation to arrest metabolism and extracted metabolites were assessed using both liquid and gas chromatography mass spectrometry (MS). Over 300 unique compounds were identified across MS platforms. Haloperidol was found to be present in all test samples and not in controls, indicating experimental validity. Twenty-one compounds differed significantly between test and control groups at the p < 0.05 level. Top compounds were robust to analytical method, also being identified via partial least squares discriminant analysis. Four compounds (sphinganine, N-acetylornithine, leucine and adenosine diphosphate) survived correction for multiple testing in a non-parametric analysis using false discovery rate threshold < 0.1. Pathway analysis of nominally significant compounds (p < 0.05) revealed significant findings for sphingolipid metabolism (p = 0.015) and protein biosynthesis (p = 0.024). Altered sphingolipid metabolism is suggestive of disruptions to myelin. This interpretation is supported by our observation of elevated N-acetyl-aspartyl-glutamate in the haloperidol-treated mice (p = 0.004), a marker previously associated with demyelination. This study further demonstrates the utility of murine neurochemical metabolomics as a method to advance understanding of CNS drug effects.

Synthesis and evaluation of three iodinated haloperidol derivatives as potential dopamine receptor imaging agents

International Nuclear Information System (INIS)

Hunter, D.H.; Strickland, L.A.; Zabel, P.L.

1990-01-01

Haloperidol, a neuroleptic which shows D-2 receptor affinity and selectivity, has been labelled primarily with positron emitting isotopes. The authors have synthesized three iodinated analogues of Haloperidol to investigate the possibility of an iodine-123 labelled agent for SPECT imaging. These compounds were obtained from the substitution of halogenated butyrophenones by halogenated arylpiperidols. In vitro and in vivo experiments will be discussed

Magnitude of increase in QTc interval after initiation of dofetilide in patients with persistent atrial fibrillation is associated with increased rates of pharmacological cardioversion and long-term freedom from recurrent atrial fibrillation.

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Huang, Henry D; Waks, Jonathan W; Steinhaus, Daniel A; Zimetbaum, Peter

2016-07-01

Dofetilide is a class III antiarrhythmic drug approved for the treatment of atrial fibrillation (AF). Dofetilide-induced corrected QT (QTc) interval prolongation is a surrogate for the degree of drug effect, but the relationships between drug-induced QTc interval prolongation, pharmacological cardioversion (PCV), and freedom from recurrent AF are unclear. The purpose of this study was to assess associations between QTc interval change during dofetilide initiation and PCV and long-term AF recurrence. We performed retrospective analyses of a prospective cohort of patients with AF admitted for dofetilide initiation between 2001 and 2014. Clinical characteristics and electrocardiographic variables were assessed. We evaluated outcomes of successful PCV in patients with persistent AF and time to recurrence of AF in patients with paroxysmal and persistent AF. During the study, 243 patients with persistent AF and 176 patients with paroxysmal AF initiated dofetilide. PCV occurred in 93/243 (41.7%) patients with persistent AF. After multivariable adjustment, QTc interval change was associated with PCV (adjusted odds ratio 1.21; P = .003 per 10-ms QTc increase). Inhospital QTc interval change was associated with long-term freedom from AF in patients with persistent AF (adjusted hazard ratio 0.92; P = .011 at 4 years per 10-ms QTc increase), but not in patients with paroxysmal AF. In patients with persistent AF, PCV was also associated with long-term freedom from recurrent AF (adjusted hazard ratio 0.62; P = .009 at 4 years). The magnitude of QTc interval prolongation during dofetilide initiation is an independent predictor of successful PCV and long-term freedom from arrhythmia in patients with persistent AF. QTc interval change had no association with AF recurrence in patients with paroxysmal AF, suggesting that different mechanisms of arrhythmogenesis may be operant in different AF types. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

First-Generation Antipsychotic Haloperidol Alters the Functionality of the Late Endosomal/Lysosomal Compartment in Vitro

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Alberto Canfrán-Duque

2016-03-01

Full Text Available First- and second-generation antipsychotics (FGAs and SGAs, respectively, have the ability to inhibit cholesterol biosynthesis and also to interrupt the intracellular cholesterol trafficking, interfering with low-density lipoprotein (LDL-derived cholesterol egress from late endosomes/lysosomes. In the present work, we examined the effects of FGA haloperidol on the functionality of late endosomes/lysosomes in vitro. In HepG2 hepatocarcinoma cells incubated in the presence of 1,1′-dioctadecyl-3,3,3,3′-tetramethylindocarbocyanineperchlorate (DiI-LDL, treatment with haloperidol caused the enlargement of organelles positive for late endosome markers lysosome-associated membrane protein 2 (LAMP-2 and LBPA (lysobisphosphatidic acid, which also showed increased content of both free-cholesterol and DiI derived from LDL. This indicates the accumulation of LDL-lipids in the late endosomal/lysosomal compartment caused by haloperidol. In contrast, LDL traffic through early endosomes and the Golgi apparatus appeared to be unaffected by the antipsychotic as the distribution of both early endosome antigen 1 (EEA1 and coatomer subunit β (β-COP were not perturbed. Notably, treatment with haloperidol significantly increased the lysosomal pH and decreased the activities of lysosomal protease and β-d-galactosidase in a dose-dependent manner. We conclude that the alkalinization of the lysosomes’ internal milieu induced by haloperidol affects lysosomal functionality.

First-Generation Antipsychotic Haloperidol Alters the Functionality of the Late Endosomal/Lysosomal Compartment in Vitro

Science.gov (United States)

Canfrán-Duque, Alberto; Barrio, Luis C.; Lerma, Milagros; de la Peña, Gema; Serna, Jorge; Pastor, Oscar; Lasunción, Miguel A.; Busto, Rebeca

2016-01-01

First- and second-generation antipsychotics (FGAs and SGAs, respectively), have the ability to inhibit cholesterol biosynthesis and also to interrupt the intracellular cholesterol trafficking, interfering with low-density lipoprotein (LDL)-derived cholesterol egress from late endosomes/lysosomes. In the present work, we examined the effects of FGA haloperidol on the functionality of late endosomes/lysosomes in vitro. In HepG2 hepatocarcinoma cells incubated in the presence of 1,1′-dioctadecyl-3,3,3,3′-tetramethylindocarbocyanineperchlorate (DiI)-LDL, treatment with haloperidol caused the enlargement of organelles positive for late endosome markers lysosome-associated membrane protein 2 (LAMP-2) and LBPA (lysobisphosphatidic acid), which also showed increased content of both free-cholesterol and DiI derived from LDL. This indicates the accumulation of LDL-lipids in the late endosomal/lysosomal compartment caused by haloperidol. In contrast, LDL traffic through early endosomes and the Golgi apparatus appeared to be unaffected by the antipsychotic as the distribution of both early endosome antigen 1 (EEA1) and coatomer subunit β (β-COP) were not perturbed. Notably, treatment with haloperidol significantly increased the lysosomal pH and decreased the activities of lysosomal protease and β-d-galactosidase in a dose-dependent manner. We conclude that the alkalinization of the lysosomes’ internal milieu induced by haloperidol affects lysosomal functionality. PMID:26999125

Haloperidol counteracts the ketamine-induced disruption of processing negativity, but not that of the P300 amplitude

DEFF Research Database (Denmark)

Oranje, Bob; Gispen-de Wied, Christine C; Westenberg, Herman G M

2009-01-01

. Besides exerting an antagonistic effect on NMDA receptors, they have agonistic effects on dopamine D2 receptors. Can haloperidol (D2 antagonist) counteract the disruptive effects of ketamine on psychophysiological parameters of human attention? In a randomized, double-blind, placebo-controlled experiment...... 18 healthy male volunteers received placebo/placebo, placebo/ketamine (0.3 mg/kg i.v.) and haloperidol (2 mg)/ketamine (0.3 mg/kg i.v.) on three separate test days, after which they were tested in an auditory selective-attention paradigm. Haloperidol/ketamine reduced task performance compared...... to placebo/placebo, while the task performance in these two treatments did not differ from placebo/ketamine. Furthermore, placebo/ketamine reduced processing negativity compared to both placebo/placebo and haloperidol/ketamine, while processing negativity did not differ between placebo...

Comparison between risperidone, an atypical antipsychotic agent and haloperidol, a conventional agent used to treat schizophrenia

International Nuclear Information System (INIS)

Rehman, A.; Jawed, M.; Maheshwari, M.P.

2012-01-01

An observational and comparative study was conducted to compare the functional outcome between the patients treated with conventional antipsychotic agent haloperidol and typical antipsychotic agent, Risperidone (Risperidal). A total of 32 patients were included in the study with established schizophrenia according to (DSM iv). The data was processed on SSPE 10th version. The primary outcome measure was the improvement of negative symptoms of schizophrenia and secondary outcome measure was to observe the superiority of the atypical drug Risperid one over conventional agent haloperidol regarding side effects. Patients were assessed at baseline, 2nd and 8th week, using four tools of assessment. For treatment group receiving haloperidol mean was 47.2+-11.50 at 8th week and for Risperidone treatment group mean was 43+-14.68. The P values for all the parameters in the Clozapine group were significant as compared to haloperidol. (author)

Ferrocene, ruthenocene or rhodocene analogues of Haloperidol. Synthesis and organ distribution after labelling with /sup 103/Ru or /sup 103m/Rh

Energy Technology Data Exchange (ETDEWEB)

Wenzel, M; Wu, Y

1988-01-01

Ferrocene-Haloperidol was synthesized by N-alkylation of 4-(4'-chlorophenyl)-4-hydroxypiperidine with 1-ferrocenyl-4-chlor-butan-1-on. By heating the ferrocene-haloperidol with /sup 103/RuCl/sub 3/ the /sup 103/Ru-labelled ruthenocene-haloperidol was obtained. This compound showed a high affinity for lung but not for brain in rats and mice. The decay of the /sup 103/Ru labelled compound results in the formation of the /sup 103m/Rh labelled rhodocene-haloperidol, which is rapidly oxidized by air to the corresponding rhodocinium-haloperidol. This compound can be separated by extraction and TLC.

Mucuna pruriens attenuates haloperidol-induced orofacial dyskinesia in rats.

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Pathan, Amjadkhan A; Mohan, Mahalaxmi; Kasture, Ameya S; Kasture, Sanjay B

2011-04-01

Neuroleptic-induced tardive dyskinesia (TD) is a motor disorder of the orofacial region resulting from chronic neuroleptic treatment. The agents improving dopaminergic transmission improve TD. Mucuna pruriens seed contains levodopa and amino acids. The effect of methanolic extract of M. pruriens seeds (MEMP) was studied on haloperidol-induced TD, alongside the changes in lipid peroxidation, reduced glutathione, superoxide dismutase (SOD) and catalase levels. The effect of MEMP was also evaluated in terms of the generation of hydroxyl and 1,1-diphenyl,2-picrylhydrazyl (DPPH) radical. MEMP (100 and 200 mg kg⁻¹) inhibited haloperidol-induced vacuous chewing movements, orofacial bursts and biochemical changes. MEMP also inhibited hydroxyl radical generation and DPPH. The results of the present study suggest that MEMP by virtue of its free radical scavenging activity prevents neuroleptic-induced TD.

Effects of haloperidol and aripiprazole on the human mesolimbic motivational system: A pharmacological fMRI study.

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Bolstad, Ingeborg; Andreassen, Ole A; Groote, Inge; Server, Andres; Sjaastad, Ivar; Kapur, Shitij; Jensen, Jimmy

2015-12-01

The atypical antipsychotic drug aripiprazole is a partial dopamine (DA) D2 receptor agonist, which differentiates it from most other antipsychotics. This study compares the brain activation characteristic produced by aripiprazole with that of haloperidol, a typical D2 receptor antagonist. Healthy participants received an acute oral dose of haloperidol, aripiprazole or placebo, and then performed an active aversive conditioning task with aversive and neutral events presented as sounds, while blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) was carried out. The fMRI task, targeting the mesolimbic motivational system that is thought to be disturbed in psychosis, was based on the conditioned avoidance response (CAR) animal model - a widely used test of therapeutic potential of antipsychotic drugs. In line with the CAR animal model, the present results show that subjects given haloperidol were not able to avoid more aversive than neutral task trials, even though the response times were shorter during aversive events. In the aripiprazole and placebo groups more aversive than neutral events were avoided. Accordingly, the task-related BOLD-fMRI response in the mesolimbic motivational system was diminished in the haloperidol group compared to the placebo group, particularly in the ventral striatum, whereas the aripiprazole group showed task-related activations intermediate of the placebo and haloperidol groups. The current results show differential effects on brain function by aripiprazole and haloperidol, probably related to altered DA transmission. This supports the use of pharmacological fMRI to study antipsychotic properties in humans. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Syntheses of 18F-labeled reduced haloperidol and 11C-labeled reduced 3-N-methylspiperone

International Nuclear Information System (INIS)

Ravert, H.T.; Dannals, R.F.; Wilson, A.A.; Wong, D.F.; Wagner, H.N. Jr.

1991-01-01

18 F-Labeled reduced haloperidol and 11 C-labeled reduced 3-N-methylspiperone were synthesized in a convenient and quantitative one step reduction from 18 F-labeled haloperidol and 11 C-labeled N-methylspiperone, respectively. Both products were purified by semipreparative HPLC and were obtained at high specific activity and radiochemical purity. (author)

The QT dispersion and QTc dispersion in patients presenting with acute neurological events and its impact on early prognosis

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Kailash Kumar Rahar

2016-01-01

Full Text Available Aims: To find out and investigate whether the QT dispersion and QTc dispersion is related to type and prognosis of the acute stroke in patients presenting within 24 h of the onset of stroke. Settings and Design: This was a observational study conducted at Mahatma Gandhi Hospital, Dr. SN. Medical College, Jodhpur, during January 2014 to January 2015. Subjects and Methods: The patients presented within 24 h of onset of acute stroke (hemorrhagic, infarction, or transient ischemic event were included in the study. The stroke was confirmed by computed tomography scan and magnetic resonance imaging. Patients with (i altered sensorium because of metabolic, infective, seizures, trauma, or tumor; (ii prior history of cardiovascular disease, electrocardiographic abnormalities' because of dyselectrolytemia; and (iii and patients who were on drugs (antiarrhythmic drugs, antipsychotic drugs, erythromycin, theophylline, etc., which known to cause electrocardiogram changes, were excluded from the study. National Institute of Health Stroke Score (NIHSS was calculated at the time of admission and Modified Rankin Scale (MRS at the time of discharge. Fifty age- and sex-matched healthy controls included. Statistical Analysis Used: Student's t-test, ANOVA, and area under curve for sensitivity and specificity for the test. Results: We included 52 patients (male/female: 27/25 and 50 controls (26/24. The mean age of patients was 63.17 ± 08.90 years. Of total patients, infarct was found in 32 (61.53%, hemorrhage in 18 (34.61%, transient ischemic attack (TIA in 1 (1.9%, and subarachnoid hemorrhage in 1 (1.9% patient. The QT dispersion and QTc dispersion were significantly higher in cases as compare to controls. (87.30 ± 24.42 vs. 49.60 ± 08.79 ms; P < 0.001 and (97.53 ± 27.36 vs. 56.28 ± 09.86 ms; P < 0.001. Among various types of stroke, the mean QT dispersion and QTc dispersion were maximum and significantly higher in hemorrhagic stroke as compared to infarct and

Lack of cross-tolerance between haloperidol and clozapine towards Fos-protein induction in rat forebrain regions

NARCIS (Netherlands)

Sebens, JB; Koch, T; Korf, J

1996-01-01

We investigated whether the acute effects of haloperidol and clozapine on Fos expression in the rat forebrain are mediated by the same receptors through evaluation of cross-tolerance, particularly in the commonly affected areas. Acutely administered haloperidol (1 mg/kg, i.p.) and clozapine (20

Midazolam Plus Haloperidol as Adjuvant Analgesics to Morphine in Opium Dependent Patients: A Randomized Clinical Trial.

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Afzalimoghaddam, Mohammad; Edalatifard, Maryam; Nejati, Amir; Momeni, Mehdi; Isavi, Nader; Karimialavijeh, Ehsan

2016-01-01

Tolerance to opioids among opium-dependent patients creates obstacles for proper pain management of these patients in the emergency department (ED). The aim of the present study was to investigate the efficacy of intramuscular (IM) haloperidol plus midazolam on morphine analgesia among opium-dependent patients. Opium-dependent adults who were admitted to the ED for new-onset severe pain in the limbs or abdomen (within 24 hours of admission and a pain score of over six, using a numerical rating scale [NRS]) were recruited. Participants were randomly assigned into two groups. Group A received morphine 0.05 mg/kg intravenously (IV) and a mixture of midazolam 2.5 mg and haloperidol 2.5 mg (diluted in 5 cc of distilled water, IM); group B received morphine 0.05 mg/kg IV and distilled water 5 cc, IM. Measured outcomes were related to: 1) pain intensity; 2) total doses of morphine; 3) changes in hemodynamic status and level of consciousness of patients. NRS scores (zero to 10) before and one, three and six hours following intervention, as well as total doses of morphine, were recorded. We recruited 68 males (78.16%) and 19 females (21.83%). The mean age was 38.28±6.59 years. The pain score in group A declined more rapidly over six hours than that in group B. Moreover, as compared to group B, the amount of morphine use decreased significantly in group A. Based on the present data, adding haloperidol plus midazolam to morphine for pain management improved pain scores and lowered morphine consumption among opium-dependent patients. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Chronic lithium treatment with or without haloperidol fails to affect the morphology of the rat cerebellum

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Licht, R W; Larsen, Jytte Overgaard; Smith, D

2003-01-01

We used unbiased stereological principles to determine whether long-term administration of lithium at human therapeutic levels, with or without haloperidol, affects the number or sizes of cerebellar Purkinje cells or the volume of histological layers in the rat cerebellum. Twenty-eight rats were...... randomly divided into three groups, receiving either no treatment, lithium, or lithium combined with haloperidol. The serum lithium levels ranged from 0.50 to 0.77 mmol/l. Haloperidol was given at a daily dose of 1 mg/kg. After 30 weeks of treatment, the animals were killed and the cerebelli were...

Intranasal haloperidol-loaded miniemulsions for brain targeting: Evaluation of locomotor suppression and in-vivo biodistribution.

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El-Setouhy, Doaa Ahmed; Ibrahim, A B; Amin, Maha M; Khowessah, Omneya M; Elzanfaly, Eman S

2016-09-20

Haloperidol is a commonly prescribed antipsychotic drug currently administered as oral and injectable preparations. This study aimed to prepare haloperidol intranasal miniemulsion helpful for psychiatric emergencies and exhibiting lower systemic exposure and side effects associated with non-target site delivery. Haloperidol miniemulsions were successfully prepared by spontaneous emulsification adopting 2(3) factorial design. The effect of three independent variables at two levels each namely; oil type (Capmul®-Capryol™90), lipophilic emulsifier type (Span 20-Span 80) and HLB value (12-14) on globule size, PDI and percent locomotor activity inhibition in mice was evaluated. The optimized formula (F4, Capmul®, Tween 80/Span 20, HLB 14) showed globule size of 209.5±0.98nm, PDI of 0.402±0.03 and locomotor inhibition of 83.89±9.15% with desirability of 0.907. Biodistribution study following intranasal and intravenous administration of the radiolabeled (99m)Tc mucoadhesive F4 revealed that intranasal administration achieved 1.72-fold higher and 6 times faster peak brain levels compared with intravenous administration. Drug targeting efficiency percent and brain/blood exposure ratios remained above 100% and 1 respectively after intranasal instillation compared to a maximum brain/blood exposure ratio of 0.8 post intravenous route. Results suggested the CNS delivery of major fraction of haloperidol via direct transnasal to brain pathway that can be a promising alternative to oral and parenteral routes in chronic and acute situations. Haloperidol concentration of 275.6ng/g brain 8h post intranasal instillation, higher than therapeutic concentration range of haloperidol (0.8 to 5.15ng/ml), suggests possible sustained delivery of the drug through nasal route. Copyright © 2016 Elsevier B.V. All rights reserved.

Antipsychotics, chlorpromazine and haloperidol inhibit voltage-gated proton currents in BV2 microglial cells.

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Shin, Hyewon; Song, Jin-Ho

2014-09-05

Microglial dysfunction and neuroinflammation are thought to contribute to the pathogenesis of schizophrenia. Some antipsychotic drugs have anti-inflammatory activity and can reduce the secretion of pro-inflammatory cytokines and reactive oxygen species from activated microglial cells. Voltage-gated proton channels on the microglial cells participate in the generation of reactive oxygen species and neuronal toxicity by supporting NADPH oxidase activity. In the present study, we examined the effects of two typical antipsychotics, chlorpromazine and haloperidol, on proton currents in microglial BV2 cells using the whole-cell patch clamp method. Chlorpromazine and haloperidol potently inhibited proton currents with IC50 values of 2.2 μM and 8.4 μM, respectively. Chlorpromazine and haloperidol are weak bases that can increase the intracellular pH, whereby they reduce the proton gradient and affect channel gating. Although the drugs caused a marginal positive shift of the activation voltage, they did not change the reversal potential. This suggested that proton current inhibition was not due to an alteration of the intracellular pH. Chlorpromazine and haloperidol are strong blockers of dopamine receptors. While dopamine itself did not affect proton currents, it also did not alter proton current inhibition by the two antipsychotics, indicating dopamine receptors are not likely to mediate the proton current inhibition. Given that proton channels are important for the production of reactive oxygen species and possibly pro-inflammatory cytokines, the anti-inflammatory and antipsychotic activities of chlorpromazine and haloperidol may be partly derived from their ability to inhibit microglial proton currents. Copyright © 2014 Elsevier B.V. All rights reserved.

Prolonged Tp-e Interval, Tp-e/QT Ratio and Tp-e/QTc Ratio in Patients with Type 2 Diabetes Mellitus

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Alptug Tokatli

2016-03-01

Full Text Available BackgroundType 2 diabetes mellitus (T2DM is associated with increased risk of malignant ventricular arrhythmias. Cardiac electrical inhomogeneity may be the leading cause of the increased arrhythmic risk in patients with T2DM. The peak and the end of the T wave (Tp-e interval and associated Tp-e/QT ratio are promising measures of ventricular repolarization indicating transmural dispersion of repolarization. The aim of this study was to assess ventricular repolarization in patients with T2DM by using Tp-e interval, Tp-e/QT ratio and Tp-e/corrected QT interval (QTc ratio.MethodsForty-three patients with T2DM and 43 healthy control subjects, matched by gender and age, were studied. All participants underwent electrocardiography (ECG recording. PR, RR and QT intervals represents the ECG intervals. These are not abbreviations. In all literature these ECG intervals are written like in this text. Tp-e intervals were measured from 12-lead ECG. Rate QTc was calculated by using the Bazett's formula. Tp-e/QT ratio and Tp-e/QTc ratio were also calculated.ResultsMean Tp-e interval was significantly prolonged in patients with T2DM compared to controls (79.4±10.3, 66.4±8.1 ms, respectively; P<0.001. We also found significantly higher values of Tp-e/QT ratio and Tp-e/QTc ratio in patients with diabetes than controls (0.21±0.03, 0.17±0.02 and 0.19±0.02, 0.16±0.02, respectively; P<0.001. There was no difference in terms of the other ECG parameters between the groups.ConclusionTp-e interval, Tp-e/QT ratio and Tp-e/QTc ratio were prolonged in patients with T2DM. We concluded that T2DM leads to augmentation of transmural dispersion of repolarization suggesting increased risk for ventricular arrhythmogenesis.

Haloperidol normalized prenatal vitamin D depletion-induced reduction of hippocampal cell proliferation in adult rats.

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Keilhoff, Gerburg; Grecksch, Gisela; Becker, Axel

2010-05-31

Considering the fact that schizophrenia is a highly complex disorder of the human brain, different models are needed to test specific causative or mechanistic hypotheses. The pathogenesis of schizophrenia is also characterized by abnormal neuronal development. It was found that schizophrenia as well as antipsychotic treatment are accompanied by alterations in neuronal proliferation. Recently we reported on increased neurogenesis and their controllability by neuroleptics in a pharmacological (ketamine) model of schizophrenia. To complete our understanding, here we studied neurogenesis and its sensitivity to the classical neuroleptic haloperidol in a developmental model of schizophrenia (maternal vitamin D deficiency). It was found that maternal vitamin D deficiency resulted in decreased neurogenesis. This effect was ameliorated by subchronic treatment with haloperidol. Thus, the results complete previous findings concerning the ability of haloperidol to ameliorate behavioral abnormalities induced by prenatal vitamin D deficiency and introduce the possibility to explain the curative effects of haloperidol, at least in part, due to re-establishment of disturbed cell proliferation. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Effect of risperidone versus haloperidol on emotional responding in schizophrenic patients.

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Fakra, E; Khalfa, S; Da Fonseca, D; Besnier, N; Delaveau, P; Azorin, J M; Blin, O

2008-10-01

Studies on emotional processing report that schizophrenic patients present a specific pattern of emotional responding that usually includes deficits in emotional expressiveness, increased feelings of unpleasant emotion but decreased feelings of pleasant emotion, and increased physiological reactivity. However, studies have rarely controlled the nature of antipsychotic medication. Yet, the influence of these drugs on emotional response is uncertain and could vary depending on their pharmacological profile. This prospective and randomized study aimed to compare the effects of an atypical antipsychotic, risperidone, to a typical one, haloperidol, on patients' emotional responding during an emotional induction task. Twenty-five schizophrenic patients underwent two emotional and clinical evaluations: one before treatment initiation and a second 4 weeks after. Emotional states of fear, sadness, anger, joy, and disgust were induced, as well as a neutral baseline state. Video recordings of patients during the induction task allowed for assessment of emotional expressiveness. Self-reports and measures of skin conductance and heart rate were performed to determine both subjective and physiological reactions to emotional experience. Compared to haloperidol, risperidone did not reduce patients' facial expressiveness, decreased physiological reactivity, and decreased experience of unpleasant emotion but maintained experience of pleasant emotion. Emotional expressiveness was negatively correlated to parkisonism. Our preliminary results suggest that atypical antipsychotics allow for better-adapted patterns of emotional responding than typical ones do. We suggest that this effect is due to reduced striatal D2 blockade, therefore, attenuating akinesia, coupled with increased 5HT and DA levels in prefrontal cortex, which improves emotional regulation.

Quetiapine versus haloperidol in the treatment of delirium: a double-blind, randomized, controlled trial

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Maneeton, Benchalak; Maneeton, Narong; Srisurapanont, Manit; Chittawatanarat, Kaweesak

2013-01-01

Background Atypical antipsychotic drugs may have low propensity to induce extrapyramidal side effects in delirious patients. This study aimed to compare the efficacy and tolerability between quetiapine and haloperidol in controlling delirious behavior. Methods A 7-day prospective, double-blind, randomized controlled trial was conducted from June 2009 to April 2011 in medically ill patients with delirium. Measures used for daily assessment included the Delirium Rating Scale-revised-98 (DRS-R-98) and total sleep time. The Clinical Global Impression, Improvement (CGI–I) and the Modified (nine-item) Simpson– Angus Scale were applied daily. The primary outcome was the DRS-R-98 severity scores. The data were analyzed on an intention-to-treat basis. Results Fifty-two subjects (35 males and 17 females) were randomized to receive 25–100 mg/day of quetiapine (n = 24) or 0.5–2.0 mg/day of haloperidol (n = 28). Mean (standard deviation) doses of quetiapine and haloperidol were 67.6 (9.7) and 0.8 (0.3) mg/day, respectively. Over the trial period, means (standard deviation) of the DRS-R-98 severity scores were not significantly different between the quetiapine and haloperidol groups (−22.9 [6.9] versus −21.7 [6.7]; P = 0.59). The DRS-R-98 noncognitive and cognitive subscale scores were not significantly different. At end point, the response and remission rates, the total sleep time, and the Modified (nine-item) Simpson–Angus scores were also not significantly different between groups. Hypersomnia was common in the quetiapine-treated patients (33.3%), but not significantly higher than that in the haloperidol-treated group (21.4%). Limitations Patients were excluded if they were not able to take oral medications, and the sample size was small. Conclusion Low-dose quetiapine and haloperidol may be equally effective and safe for controlling delirium symptoms. Clinical trials registration number clinicaltrials.gov NCT00954603. PMID:23926422

Genetics of Adverse Reactions to Haloperidol in a Mouse Diallel: A Drug–Placebo Experiment and Bayesian Causal Analysis

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Crowley, James J.; Kim, Yunjung; Lenarcic, Alan B.; Quackenbush, Corey R.; Barrick, Cordelia J.; Adkins, Daniel E.; Shaw, Ginger S.; Miller, Darla R.; de Villena, Fernando Pardo-Manuel; Sullivan, Patrick F.; Valdar, William

2014-01-01

Haloperidol is an efficacious antipsychotic drug that has serious, unpredictable motor side effects that limit its utility and cause noncompliance in many patients. Using a drug–placebo diallel of the eight founder strains of the Collaborative Cross and their F1 hybrids, we characterized aggregate effects of genetics, sex, parent of origin, and their combinations on haloperidol response. Treating matched pairs of both sexes with drug or placebo, we measured changes in the following: open field activity, inclined screen rigidity, orofacial movements, prepulse inhibition of the acoustic startle response, plasma and brain drug level measurements, and body weight. To understand the genetic architecture of haloperidol response we introduce new statistical methodology linking heritable variation with causal effect of drug treatment. Our new estimators, “difference of models” and “multiple-impute matched pairs”, are motivated by the Neyman–Rubin potential outcomes framework and extend our existing Bayesian hierarchical model for the diallel (Lenarcic et al. 2012). Drug-induced rigidity after chronic treatment was affected by mainly additive genetics and parent-of-origin effects (accounting for 28% and 14.8% of the variance), with NZO/HILtJ and 129S1/SvlmJ contributions tending to increase this side effect. Locomotor activity after acute treatment, by contrast, was more affected by strain-specific inbreeding (12.8%). In addition to drug response phenotypes, we examined diallel effects on behavior before treatment and found not only effects of additive genetics (10.2–53.2%) but also strong effects of epistasis (10.64–25.2%). In particular: prepulse inhibition showed additivity and epistasis in about equal proportions (26.1% and 23.7%); there was evidence of nonreciprocal epistasis in pretreatment activity and rigidity; and we estimated a range of effects on body weight that replicate those found in our previous work. Our results provide the first

Haloperidol plasmatic levels and their clinical response to the treatment. Comparison between the radioimmunoassay and radioreceptorassay: preliminary data

Energy Technology Data Exchange (ETDEWEB)

Cabranes, J A; Almoguera, I; Santos, J L; Prieto, P; Ramos, J A

1988-06-01

Schizophrenic patients were treated with haloperidol. Their haloperidol levels in plasma were determined with radioimmunoassay (RIA) and radioreceptor assay (RRA). The results obtained are compared with the clinical improvement. (M.C.B.).

Significance of screening electrocardiogram before the initiation of amitriptyline therapy in children with functional abdominal pain.

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Patra, Kamakshya P; Sankararaman, Senthilkumar; Jackson, Robert; Hussain, Sunny Z

2012-09-01

Amitriptyline (AMT) is commonly used in the management of children with irritable bowel syndrome. AMT is pro-arrhythmogenic and increases the risk of sudden cardiac death. However, there is not enough data regarding the cardiac toxicity in therapeutic doses of AMT in children and the need for screening electrocardiogram (EKG). Errors in computer EKG interpretation are not uncommon. In a risk-prevention study, the authors sought to identify the true incidence of prolonged corrected QT (QTc) interval and other arrhythmias in children with irritable bowel syndrome before the initiation of AMT. Out of the 760 EKGs screened, 3 EKGs demonstrated a true prolonged QTc after the careful manual reading by a pediatric cardiologist and they were not picked by computer-generated reading. The authors conclude that screening EKG should always be performed on children before initiating AMT therapy. Also, the computer-generated EKG needs to be verified by a pediatric cardiologist to avoid serious misinterpretations.

Genetic basis of haloperidol resistance in Saccharomyces cerevisiae is complex and dose dependent.

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Xin Wang

2014-12-01

Full Text Available The genetic basis of most heritable traits is complex. Inhibitory compounds and their effects in model organisms have been used in many studies to gain insights into the genetic architecture underlying quantitative traits. However, the differential effect of compound concentration has not been studied in detail. In this study, we used a large segregant panel from a cross between two genetically divergent yeast strains, BY4724 (a laboratory strain and RM11_1a (a vineyard strain, to study the genetic basis of variation in response to different doses of a drug. Linkage analysis revealed that the genetic architecture of resistance to the small-molecule therapeutic drug haloperidol is highly dose-dependent. Some of the loci identified had effects only at low doses of haloperidol, while other loci had effects primarily at higher concentrations of the drug. We show that a major QTL affecting resistance across all concentrations of haloperidol is caused by polymorphisms in SWH1, a homologue of human oxysterol binding protein. We identify a complex set of interactions among the alleles of the genes SWH1, MKT1, and IRA2 that are most pronounced at a haloperidol dose of 200 µM and are only observed when the remainder of the genome is of the RM background. Our results provide further insight into the genetic basis of drug resistance.

Genetic Basis of Haloperidol Resistance in Saccharomyces cerevisiae Is Complex and Dose Dependent

Science.gov (United States)

Wang, Xin; Kruglyak, Leonid

2014-01-01

The genetic basis of most heritable traits is complex. Inhibitory compounds and their effects in model organisms have been used in many studies to gain insights into the genetic architecture underlying quantitative traits. However, the differential effect of compound concentration has not been studied in detail. In this study, we used a large segregant panel from a cross between two genetically divergent yeast strains, BY4724 (a laboratory strain) and RM11_1a (a vineyard strain), to study the genetic basis of variation in response to different doses of a drug. Linkage analysis revealed that the genetic architecture of resistance to the small-molecule therapeutic drug haloperidol is highly dose-dependent. Some of the loci identified had effects only at low doses of haloperidol, while other loci had effects primarily at higher concentrations of the drug. We show that a major QTL affecting resistance across all concentrations of haloperidol is caused by polymorphisms in SWH1, a homologue of human oxysterol binding protein. We identify a complex set of interactions among the alleles of the genes SWH1, MKT1, and IRA2 that are most pronounced at a haloperidol dose of 200 µM and are only observed when the remainder of the genome is of the RM background. Our results provide further insight into the genetic basis of drug resistance. PMID:25521586

Adjunctive treatment of manic agitation with lorazepam versus haloperidol: a double-blind study.

Science.gov (United States)

Lenox, R H; Newhouse, P A; Creelman, W L; Whitaker, T M

1992-02-01

While lithium is effective in treating the majority of bipolar patients during a manic episode, the addition of neuroleptic during the early phase of treatment has been common clinical practice in inpatient settings. In an earlier open study, we demonstrated the utility of the short-acting benzodiazepine lorazepam as an adjunct to lithium for the clinical management of manic agitation. We now present data from a randomized, double-blind clinical study of lorazepam versus haloperidol in 20 hospitalized patients with a DSM-III-R diagnosis of bipolar disorder who were being treated concomitantly with lithium. Patients were rated using the Mania Rating Scale, Brief Psychiatric Rating Scale, Physician Global Impression Scale, and side effects scales. Data were analyzed using standard group comparisons and survival analysis. There was no evidence for a significant difference between the two treatment groups in the magnitude of or time to response (5.0 +/- .82 days for haloperidol; 6.5 +/- .93 days for lorazepam). Of the patients who were terminated from the protocol early, nonresponse was the primary reason in the lorazepam group while side effects were the reason in the haloperidol group. Lorazepam may offer an efficacious and safe alternative to haloperidol as an adjunctive treatment to lithium in the clinical management of the early phase of manic agitation in a subgroup of bipolar patients.

Antagonism by supidimide of haloperidol-induced augmentation of (/sup 3/H)-spiperone binding in rat striatum

Energy Technology Data Exchange (ETDEWEB)

Hennies, H H; Hess, V; Flohe, L

1984-01-01

Rats were treated for two weeks with haloperidol alone or with additional test drugs and the D/sub 2/ receptor density in the striatum was investigated after a drug-free period of five days. The D/sub 2/ receptor system as analysed by (/sup 3/H)-spinerone binding was best characterized by a model with two binding sites of different affinity. Chronic haloperidol treatment substantially augmented the total binding capacity 2-(2-Oxo-3-piperidyl)-1,2-benzisothiazoline-3-one-1,1-dioxide (supidimide), a functional synergist of neuroleptics in acute experiments, surprisingly antagonized the haloperidol-induced receptor augmentation, whereas other CNS depressants (diazepam and phenobarbital) were ineffective.

Characterization with 3H-haloperidol of the dopamine receptor in the rat kidney particulate preparation

International Nuclear Information System (INIS)

Nakajima, Tohru; Kuruma, Isami

1980-01-01

The dopamine receptor of rat kidney particulate preparation was identified and characterized by the use of 3 H-haloperidol binding. Binding of 3 H-haloperidol to the kidney particulate preparation was slow and saturable. The dissociation constants (K sub(D)) were 0.41 nM and 5.88 nM, respectively, according to the model of two classes of independent binding sites. Maximal binding of high affinity site was obtained with 166 fmole/mg protein which was about 40% of the total receptor density. A wide variety of neuroleptics at specifically low concentrations in nanomolar range inhibited the 3 H-haloperidol binding. There was an excellent correlation between the affinity of numerous neuroleptics for the kidney particulate preparation and that for the brain striatum. (author)

Effect of haloperidol on the synthesis of DNA in the pituitary gland of the rat.

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Machiavelli, G A; Jahn, G A; Kalbermann, L E; Szijan, I; Alonso, G E; Burdman, J A

1982-03-01

The administration of haloperidol increased serum prolactin and decreased the pituitary concentration of prolactin 15 min after its administration. Concomitantly there was a stimulation in the synthesis of DNA and the activity of DNA polymerase alpha in the anterior pituitary gland that was greater in oestrogenized than in non-oestrogenized male rats. Both these effects were greatly reduced by clomiphene in the oestrogenized male rats, although it did not affect the release of prolactin produced by haloperidol. In non-oestrogenized animals clomiphene abolished the stimulatory effect of haloperidol on the synthesis of DNA. These results suggest that the reduction in the intracellular levels of prolactin are a primary event in the oestrogen mediated stimulation of cell proliferation by prolactin releasing agents.

Bauhinia forficata prevents vacuous chewing movements induced by haloperidol in rats and has antioxidant potential in vitro.

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Peroza, Luis Ricardo; Busanello, Alcindo; Leal, Caroline Queiroz; Röpke, Jivago; Boligon, Aline Augusti; Meinerz, Daiane; Libardoni, Milena; Athayde, Margareth Linde; Fachinetto, Roselei

2013-04-01

Classical antipsychotics can produce motor disturbances like tardive dyskinesia in humans and orofacial dyskinesia in rodents. These motor side effects have been associated with oxidative stress production in specific brain areas. Thus, some studies have proposed the use of natural compounds with antioxidant properties against involuntary movements induced by antipsychotics. Here, we examined the possible antioxidant activity of Bauhinia forficata (B. forficata), a plant used in folk medicine as a hypoglycemic, on brain lipid peroxidation induced by different pro-oxidants. B. forficata prevented the formation of lipid peroxidation induced by both pro-oxidants tested. However, it was effective against lipid peroxidation induced by sodium nitroprusside (IC50 = 12.08 μg/mL) and Fe(2+)/EDTA (IC50 = 41.19 μg/mL). Moreover, the effects of B. forficata were analyzed on an animal model of orofacial dyskinesia induced by long-term treatment with haloperidol, where rats received haloperidol each 28 days (38 mg/kg) and/or B. forficata decoction daily (2.5 g/L) for 16 weeks. Vacuous chewing movements (VCMs), locomotor and exploratory activities were evaluated. Haloperidol treatment induced VCMs, and co-treatment with B. forficata partially prevented this effect. Haloperidol reduced the locomotor and exploratory activities of animals in the open field test, which was not modified by B. forficata treatment. Our present data showed that B. forficata has antioxidant potential and partially protects against VCMs induced by haloperidol in rats. Taken together, our data suggest the protection by natural compounds against VCMs induced by haloperidol in rats.

Ramipril and haloperidol as promising approaches in managing rheumatoid arthritis in rats.

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Fahmy Wahba, Mariam Gamal; Shehata Messiha, Basim Anwar; Abo-Saif, Ali Ahmed

2015-10-15

Rheumatoid arthritis (RA) is a challenging autoimmune disorder, whose treatments usually cause severe gastrointestinal, renal and other complications. We aimed to evaluate the beneficial anti-arthritic effects of an angiotensin converting enzyme (ACE) inhibitor, ramipril and a dopamine receptor blocker, haloperidol, on Complete Freund's Adjuvant-induced RA in adult female albino rats. Rats were allocated into a normal control group, an arthritis control group, two reference treatment groups receiving dexamethasone (1.5 mg/kg/day) and methotrexate (1 mg/kg/day), and two treatment groups receiving ramipril (0.9 mg/kg/day) and haloperidol (1 mg/kg/day). Serum rheumatoid factor, matrix metalloprotinease-3 (MMP-3) and cartilage oligomeric matrix protein as specific rheumatoid biomarkers, serum immunoglobulin G and antinuclear antibody as immunological biomarkers, serum tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10) as immunomodulatory cytokines, serum myeloperoxidase and C-reactive protein as inflammatory biomarkers, as well as malondialdehyde and glutathione reduced (GSH) as oxidative stress biomarkers were assessed. A histopathological study on joints and spleens was performed to support the results of biochemical estimations. Ramipril administration significantly corrected all the measured biomarkers, being restored back to normal levels except for MMP-3, TNF-α and IL-10. Haloperidol administration restored all the measured biomarkers back to normal levels except for TNF-α, IL-10 and GSH. In conclusion, ACE inhibitors represented by ramipril and dopamine receptor blockers represented by haloperidol may represent new promising protective strategies against RA, at least owing to their immunomodulatory, anti-inflammatory and antioxidant potentials. Copyright © 2015 Elsevier B.V. All rights reserved.

Haloperidol, risperidone, olanzapine and aripiprazole in the management of delirium: A comparison of efficacy, safety, and side effects.

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Boettger, Soenke; Jenewein, Josef; Breitbart, William

2015-08-01

The aim of this study was to compare the efficacy and side-effect profile of the typical antipsychotic haloperidol with that of the atypical antipsychotics risperidone, olanzapine, and aripiprazole in the management of delirium. The Memorial Delirium Assessment Scale (MDAS), the Karnofsky Performance Status (KPS) scale, and a side-effect rating were recorded at baseline (T1), after 2-3 days (T2), and after 4-7 days (T3). Some 21 cases were case-matched by age, preexisting dementia, and baseline MDAS scores, and subsequently analyzed. The baseline characteristics of the medication groups were not different: The mean age of the patients ranged from 64.0 to 69.6 years, dementia was present in between 23.8 and 28.6%, and baseline MDAS scores were 19.9 (haloperidol), 18.6 (risperidone), 19.4 (olanzapine), and 18.0 (aripiprazole). The doses of medication at T3 were 5.5 mg haloperidol, 1.3 mg risperidone, 7.1 mg olanzapine, and 18.3 mg aripiprazole. Over one week, the decline in MDAS scores between medications was equal, and no differences between individual MDAS scores existed at T2 or T3. After one week, the MDAS scores were 6.8 (haloperidol), 7.1 (risperidone), 11.7 (olanzapine), and 8.3 (aripiprazole). At T2, delirium resolution occurred in 42.9-52.4% of cases and at T3 in 61.9-85.7%; no differences in assessments between medications existed. Recorded side effects were extrapyramidal symptoms (EPSs) in haloperidol- and risperidone-managed patients (19 and 4.8%, respectively) and sedation with olanzapine (28.6%). Haloperidol, risperidone, aripiprazole, and olanzapine were equally effective in the management of delirium; however, they differed in terms of their side-effect profile. Extrapyramidal symptoms were most frequently recorded with haloperidol, and sedation occurred most frequently with olanzapine.

Haloperidol attenuates Methylphenidate and Modafinil induced behavioural sensitization and cognitive enhancement.

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Alam, Nausheen; Choudhary, Kulsoom

2018-06-01

Previous studies have demonstrated that repeated psychostimulant administration produces behavioural sensitization and cognitive tolerance. Brain dopaminergic system and the involvement of dopamine D 2 -receptors are considered to be important in psychostimulant-induced sensitization. Study designed to compared the motor activity by using familiar and novel enviroments and cognitive effects by water maze and passive avoidance test after long term administration of methylphenidate(at the dose 0.6 mg/kg/day, 2.5 mg/kg/day and 10 mg/kg/day) and modafinil (50 mg/kg/day, 64 mg/kg/day and 75 mg/kg/day) in rats. The effects of challenge dose of haloperidol (at the dose of 1 mg/kg i.p.) has monitored to visualize any subsensitization or supersensitization of D 2 receptors. We found that motor activity and cognitive performance was increased in all doses and sensitization effect was more pronounced after 13 days of drug administration were greater at high than low and medium doses.Challenge dose of haloperidol attenuate motor activity in familiar and novel environment and impaired cognition in water maze and passive avoidance test in all treated rats. The effect of Haloperidol in high dose treated rats were however somewhat greater than low and medium dose treated rats following methylphenidate and modafinil administration. Increased response of haloperidol in methylphenidate treated rats can be explained in term of supersensitization of D 2 receptors which is greater in high dose treated rats. The results show that the role of D 2 receptors to develop side effects such as behavioural sensitization and cognitive tolerance by the long term administration of psychostimulants is of sufficient importance and helpful in understanding the mechanisms underlying the undesirable effects of psychostimulants.

Long-term treatment with haloperidol affects neuropeptide S and NPSR mRNA levels in the rat brain.

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Palasz, Artur; Rojczyk, Ewa; Golyszny, Milosz; Filipczyk, Lukasz; Worthington, John J; Wiaderkiewicz, Ryszard

2016-04-01

The brainstem-derived neuropeptide S (NPS) has a multidirectional regulatory activity, especially as a potent anxiolytic factor. Accumulating data suggests that neuroleptics affect peptidergic signalling in various brain structures. However, there is no information regarding the influence of haloperidol on NPS and NPS receptor (NPSR) expression. We assessed NPS and NPSR mRNA levels in brains of rats treated with haloperidol using quantitative real-time polymerase chain reaction. Chronic haloperidol treatment (4 weeks) led to a striking upregulation of NPS and NPSR expression in the rat brainstem. Conversely, the NPSR mRNA expression was decreased in the hippocampus and striatum. This stark increase of NPS in response to haloperidol treatment supports the hypothesis that this neuropeptide is involved in the dopamine-dependent anxiolytic actions of neuroleptics and possibly also in the pathophysiology of mental disorders. Furthermore, our findings underline the complex nature of potential interactions between dopamine receptors and brain peptidergic pathways, which has potential clinical applications.

Haloperidol prophylaxis for preventing aggravation of postoperative delirium in elderly patients: a randomized, open-label prospective trial.

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Fukata, Shinji; Kawabata, Yasuji; Fujishiro, Ken; Kitagawa, Yuichi; Kuroiwa, Kojiro; Akiyama, Hirotoshi; Takemura, Marie; Ando, Masahiko; Hattori, Hideyuki

2017-07-01

The aim of this study was to evaluate the safety and efficacy of the early administration haloperidol in preventing the aggravation of postoperative delirium in elderly patients. A total of 201 patients (age ≥75 years) who underwent elective surgery were enrolled. The patients were divided into two groups: the intervention group (n = 101) received prophylactic haloperidol (5 mg); the control group (n = 100) did not. Haloperidol was administered daily during postoperative days 0-5 to the patients who presented with NEECHAM scores of 20-24 when measured at 18:00. The primary endpoint was the incidence of severe postoperative delirium. The incidence of severe postoperative delirium in all patients was 25.1%. The incidence of severe postoperative delirium in the intervention group (18.2%) was significantly lower than that in the control group (32.0%) (p = 0.02). The difference between the two groups was larger when the analysis was limited to the 70 patients who had NEECHAM scores of 20-24 for at least one day during postoperative days 0-5. No adverse effects of the haloperidol were observed. The prophylactic administration of haloperidol at the early stage of delirium significantly reduced the incidence of severe postoperative delirium in elderly patients. Clinical Trial Registration UMIN000007204.

Characterization with /sup 3/H-haloperidol of the dopamine receptor in the rat kidney particulate preparation

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Nakajima, T; Kuruma, I [Nippon Roche Research Center, Kanagawa (Japan)

1980-12-01

The dopamine receptor of rat kidney particulate preparation was identified and characterized by the use of /sup 3/H-haloperidol binding. Binding of /sup 3/H-haloperidol to the kidney particulate preparation was slow and saturable. The dissociation constants (K sub(D)) were 0.41 nM and 5.88 nM, respectively, according to the model of two classes of independent binding sites. Maximal binding of high affinity site was obtained with 166 fmole/mg protein which was about 40% of the total receptor density. A wide variety of neuroleptics at specifically low concentrations in nanomolar range inhibited the /sup 3/H-haloperidol binding. There was an excellent correlation between the affinity of numerous neuroleptics for the kidney particulate preparation and that for the brain striatum.

Association of cumulative dose of haloperidol with next-day delirium in older medical ICU patients.

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Pisani, Margaret A; Araujo, Katy L B; Murphy, Terrence E

2015-05-01

To evaluate the association between cumulative dose of haloperidol and next-day diagnosis of delirium in a cohort of older medical ICU patients, with adjustment for its time-dependent confounding with fentanyl and intubation. Prospective, observational study. Medical ICU at an urban, academic medical center. Age 60 years and older admitted to the medical ICU who received at least one dose of haloperidol (n = 93). Of these, 72 patients were intubated at some point in their medical ICU stay, whereas 21 were never intubated. None. Detailed data were collected concerning time, dosage, route of administration of all medications, as well as for important clinical covariates, and daily status of intubation and delirium using the confusion assessment method for the ICU and a chart-based algorithm. Among nonintubated patients, and after adjustment for time-dependent confounding and important covariates, each additional cumulative milligram of haloperidol was associated with 5% higher odds of next-day delirium with odds ratio of 1.05 (credible interval [CI], 1.02-1.09). After adjustment for time-dependent confounding and covariates, intubation was associated with a five-fold increase in odds of next-day delirium with odds ratio of 5.66 (CI, 2.70-12.02). Cumulative dose of haloperidol among intubated patients did not change their already high likelihood of next-day delirium. After adjustment for time-dependent confounding, the positive associations between indicators of intubation and of cognitive impairment and next-day delirium became stronger. These results emphasize the need for more studies regarding the efficacy of haloperidol for treatment of delirium among older medical ICU patients and demonstrate the value of assessing nonintubated patients.

Comparison of Haloperidol Alone and in Combination with Midazolam for the Treatment of Acute Agitation in an Inpatient Palliative Care Service.

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Ferraz Gonçalves, José António; Almeida, Ana; Costa, Isabel; Silva, Paula; Carneiro, Rui

2016-12-01

Agitation is a very distressing problem that must be controlled as quickly as possible, but using a safe method. The authors conducted a comparison of two protocols: a combination of haloperidol and midazolam and haloperidol alone. The combination drug protocol controlled 101 out of 121 (84%) episodes of agitation with only the first dose, whereas the haloperidol alone protocol controlled 47 out of 74 (64%) episodes. This difference is statistically significant (P =.002), with a post hoc analyzed power of 0.88. The median time from the first dose to the control of agitation was 15 minutes (range: 5-210) with the combination and 60 minutes (range: 10-430) with the other protocol, P haloperidol and midazolam is effective and safe for the control of agitation in palliative care and it is more effective than haloperidol alone. Therefore, the combination should be adopted as the preferred protocol. It would be helpful if the usefulness of this protocol is confirmed by others.

QT interval prolongation related to psychoactive drug treatment: a comparison of monotherapy versus polytherapy

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Piccinelli Marco

2005-01-01

Full Text Available Abstract Background Several antipsychotic agents are known to prolong the QT interval in a dose dependent manner. Corrected QT interval (QTc exceeding a threshold value of 450 ms may be associated with an increased risk of life threatening arrhythmias. Antipsychotic agents are often given in combination with other psychotropic drugs, such as antidepressants, that may also contribute to QT prolongation. This observational study compares the effects observed on QT interval between antipsychotic monotherapy and psychoactive polytherapy, which included an additional antidepressant or lithium treatment. Method We examined two groups of hospitalized women with Schizophrenia, Bipolar Disorder and Schizoaffective Disorder in a naturalistic setting. Group 1 was composed of nineteen hospitalized women treated with antipsychotic monotherapy (either haloperidol, olanzapine, risperidone or clozapine and Group 2 was composed of nineteen hospitalized women treated with an antipsychotic (either haloperidol, olanzapine, risperidone or quetiapine with an additional antidepressant (citalopram, escitalopram, sertraline, paroxetine, fluvoxamine, mirtazapine, venlafaxine or clomipramine or lithium. An Electrocardiogram (ECG was carried out before the beginning of the treatment for both groups and at a second time after four days of therapy at full dosage, when blood was also drawn for determination of serum levels of the antipsychotic. Statistical analysis included repeated measures ANOVA, Fisher Exact Test and Indipendent T Test. Results Mean QTc intervals significantly increased in Group 2 (24 ± 21 ms however this was not the case in Group 1 (-1 ± 30 ms (Repeated measures ANOVA p Conclusions No significant prolongation of the QT interval was found following monotherapy with an antipsychotic agent, while combination of these drugs with antidepressants caused a significant QT prolongation. Careful monitoring of the QT interval is suggested in patients taking a

Deficits in latent inhibition induced by estradiol replacement are ameliorated by haloperidol treatment

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Anne eAlmey

2013-10-01

Full Text Available There are sex differences in the symptomatology of schizophrenia, and in the response to antipsychotic treatments. One hallmark symptom of schizophrenia is a deficit in selective attention. Selective attention can be measured using a latent inhibition (LI paradigm in humans; LI can be measured in rodents, and is used as an animal model of the selective attention deficits observed in schizophrenia. In the current experiments LI was used to clarify whether selective attention differs between male rats and ovariectomized (OVX female rats receiving different estradiol (E2 replacement regimens. An additional aim was to determine whether haloperidol's facilitation of LI is enhanced by E2. Males and OVX female rats were trained in a conditioned emotional response LI paradigm. Females received no E2 replacement, a chronic low dose of E2 via silastic capsule, or a high phasic dose of E2 via silastic capsule accompanied by E2 (10 ug/kg SC injections every fourth day. Actual plasma levels of E2 were determined using an enzyme linked immunosorbent assay. Rats were also administered a vehicle treatment, a 0.05mg/kg, or a 0.1mg/kg IP injection of haloperidol. Males and OVX females that did not receive E2 replacement both exhibited LI, but LI was not observed in the low and high E2 replacement groups. Haloperidol restored LI at a lower dose in the females receiving high E2 replacement compared to females receiving low E2 replacement, indicating that E2 replacement facilitates haloperidol in restoring LI.

Drug–drug conditioning between citalopram and haloperidol or olanzapine in a conditioned avoidance response model: implications for polypharmacy in schizophrenia

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Sparkman, Nathan L.; Li, Ming

2016-01-01

Patients with schizophrenia often have anxiety and depression, and thus are treated with multiple psychotherapeutic medications. This practice of polypharmacy increases the possibility for drug–drug interactions. However, the pharmacological and behavioral mechanisms underlying drug–drug interactions in schizophrenia remain poorly understood. In the present study, we adopted a preclinical approach and examined a less known behavioral mechanism, drug–drug conditioning (DDC) between haloperidol (a typical antipsychotic) or olanzapine (atypical antipsychotic) and citalopram (a selective serotonin reuptake inhibitor). A rat two-way conditioned avoidance response paradigm was used to measure antipsychotic activity and determine how DDC may alter the antipsychotic efficacy in this model. Following acquisition of the avoidance response, rats were then randomly assigned to receive vehicle, citalopram (10.0 mg/kg, intraperitoneally), haloperidol (0.05 mg/kg, subcutaneously), olanzapine (1.0 mg/kg, subcutaneously), combined haloperidol with citalopram, or combined olanzapine with citalopram treatment for seven avoidance test sessions. In comparison with antipsychotic treatment alone, combined treatment with citalopram potentiated the antiavoidance effect of olanzapine or haloperidol (to a lesser extent) during the seven drug-test sessions. In addition, repeated pairing of citalopram with haloperidol or olanzapine caused citalopram to show a newly acquired avoidance-disruptive effect. This effect was context specific because citalopram paired with haloperidol or olanzapine outside the avoidance testing context (i.e. home cages) did not show such an effect. These findings indicate that concurrent antidepressant and antipsychotic treatments may engender a DDC process that follows the general Pavlovian associative conditioning principles. They also indicate that adjunctive citalopram treatment may enhance the antipsychotic efficacy of haloperidol and olanzapine in the

Intraoperative haloperidol does not improve quality of recovery and postoperative analgesia

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Amin Ebneshahidi

2013-01-01

Conclusion: Intraoperative small-dose IV haloperidol is effective against post-operative nausea and vomiting with no significant effect on overall QoR. It may also attenuate the analgesic effects of morphine PCA.

The Role of Abcb5 Alleles in Susceptibility to Haloperidol-Induced Toxicity in Mice and Humans

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Zheng, Ming; Zhang, Haili; Dill, David L.; Clark, J. David; Tu, Susan; Yablonovitch, Arielle L.; Tan, Meng How; Zhang, Rui; Rujescu, Dan; Wu, Manhong; Tessarollo, Lino; Vieira, Wilfred; Gottesman, Michael M.; Deng, Suhua; Eberlin, Livia S.; Zare, Richard N.; Billard, Jean-Martin; Gillet, Jean-Pierre; Li, Jin Billy; Peltz, Gary

2015-01-01

Background We know very little about the genetic factors affecting susceptibility to drug-induced central nervous system (CNS) toxicities, and this has limited our ability to optimally utilize existing drugs or to develop new drugs for CNS disorders. For example, haloperidol is a potent dopamine antagonist that is used to treat psychotic disorders, but 50% of treated patients develop characteristic extrapyramidal symptoms caused by haloperidol-induced toxicity (HIT), which limits its clinical utility. We do not have any information about the genetic factors affecting this drug-induced toxicity. HIT in humans is directly mirrored in a murine genetic model, where inbred mouse strains are differentially susceptible to HIT. Therefore, we genetically analyzed this murine model and performed a translational human genetic association study. Methods and Findings A whole genome SNP database and computational genetic mapping were used to analyze the murine genetic model of HIT. Guided by the mouse genetic analysis, we demonstrate that genetic variation within an ABC-drug efflux transporter (Abcb5) affected susceptibility to HIT. In situ hybridization results reveal that Abcb5 is expressed in brain capillaries, and by cerebellar Purkinje cells. We also analyzed chromosome substitution strains, imaged haloperidol abundance in brain tissue sections and directly measured haloperidol (and its metabolite) levels in brain, and characterized Abcb5 knockout mice. Our results demonstrate that Abcb5 is part of the blood-brain barrier; it affects susceptibility to HIT by altering the brain concentration of haloperidol. Moreover, a genetic association study in a haloperidol-treated human cohort indicates that human ABCB5 alleles had a time-dependent effect on susceptibility to individual and combined measures of HIT. Abcb5 alleles are pharmacogenetic factors that affect susceptibility to HIT, but it is likely that additional pharmacogenetic susceptibility factors will be discovered

The role of Abcb5 alleles in susceptibility to haloperidol-induced toxicity in mice and humans.

KAUST Repository

Zheng, Ming

2015-02-03

We know very little about the genetic factors affecting susceptibility to drug-induced central nervous system (CNS) toxicities, and this has limited our ability to optimally utilize existing drugs or to develop new drugs for CNS disorders. For example, haloperidol is a potent dopamine antagonist that is used to treat psychotic disorders, but 50% of treated patients develop characteristic extrapyramidal symptoms caused by haloperidol-induced toxicity (HIT), which limits its clinical utility. We do not have any information about the genetic factors affecting this drug-induced toxicity. HIT in humans is directly mirrored in a murine genetic model, where inbred mouse strains are differentially susceptible to HIT. Therefore, we genetically analyzed this murine model and performed a translational human genetic association study.A whole genome SNP database and computational genetic mapping were used to analyze the murine genetic model of HIT. Guided by the mouse genetic analysis, we demonstrate that genetic variation within an ABC-drug efflux transporter (Abcb5) affected susceptibility to HIT. In situ hybridization results reveal that Abcb5 is expressed in brain capillaries, and by cerebellar Purkinje cells. We also analyzed chromosome substitution strains, imaged haloperidol abundance in brain tissue sections and directly measured haloperidol (and its metabolite) levels in brain, and characterized Abcb5 knockout mice. Our results demonstrate that Abcb5 is part of the blood-brain barrier; it affects susceptibility to HIT by altering the brain concentration of haloperidol. Moreover, a genetic association study in a haloperidol-treated human cohort indicates that human ABCB5 alleles had a time-dependent effect on susceptibility to individual and combined measures of HIT. Abcb5 alleles are pharmacogenetic factors that affect susceptibility to HIT, but it is likely that additional pharmacogenetic susceptibility factors will be discovered.ABCB5 alleles alter susceptibility to

Syntheses of sup 18 F-labeled reduced haloperidol and sup 11 C-labeled reduced 3-N-methylspiperone

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Ravert, H T; Dannals, R F; Wilson, A A; Wong, D F; Wagner, Jr, H N [Johns Hopkins Medical Institutions, Baltimore, MD (USA)

1991-03-01

{sup 18}F-Labeled reduced haloperidol and {sup 11}C-labeled reduced 3-N-methylspiperone were synthesized in a convenient and quantitative one step reduction from {sup 18}F-labeled haloperidol and {sup 11}C-labeled N-methylspiperone, respectively. Both products were purified by semipreparative HPLC and were obtained at high specific activity and radiochemical purity. (author).

The influence of CYP3A5 polymorphisms on haloperidol treatment in patients with alcohol addiction

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Zastrozhin MS

2017-12-01

Full Text Available Mikhail Sergeevich Zastrozhin,1,2 Elena Anatolievna Grishina,1 Kristina Anatolievna Ryzhikova,1 Valery Valerievich Smirnov,3 Ludmila Mikhailovna Savchenko,1 Evgeny Alekseevich Bryun,1,2 Dmitry Alekseevich Sychev1 1Russian Medical Academy of Continuous Professional Education, Ministry of Health of the Russian Federation, 2Moscow Research and Practical Centre on Addictions, Moscow Department of Healthcare, 3National Research Center Institute of Immunology, Federal Medical-Biological Agency, Moscow, Russia Background: Isoenzymes CYP2D6 and CYP3A4, the activity of which varies widely, are involved in metabolism of haloperidol and may influence its profile of efficacy and safety.Objective: The primary aim of this study was to estimate the relationship between CYP3A5 gene polymorphism, activity of the CYP3A isoenzyme, and the risk of development of adverse drug reactions by haloperidol in patients with alcohol abuse.Methods: Sixty-six male alcohol-addicted patients participated in the study. The safety of haloperidol was evaluated by Udvalg for Kliniske Undersogelser Side Effect Rating Scale (UKU and Simpson–Angus Scale for extrapyramidal symptoms (SAS. The activity of CYP3A was evaluated by determining the concentrations of an endogenous substrate of this isoenzyme (cortisol and its urinary metabolite (6-beta-hydroxycortisol, 6-B-HC. Genotyping of CYP3A5*3 was performed by real-time polymerase chain reaction with allele-specific hybridization.Results: The frequency of A-allele occurrence in Russian population was very poor (2.27%. CYP3A5*3 polymorphism had no influence on safety profile indicators of haloperidol (UKU scale: p=0.55, SAS scale: p=0.64. In addition, there was no statistical significant difference between the values of indexes of the metabolic ratio (6-B-HC/cortisol in groups with different genotypes of CYP3A5*3: GG 5.00 (3.36; 6.39 vs AG 5.26 (2.10; 6.78 (p=0.902.Conclusion: The frequency of A-allele occurrence of CYP3A5*3 in Russian

METABOLIC SIDE EFFECTS OF HALOPERIDOL AND RISPERIDONE- A SIX MONTHS FOLLOWUP STUDY

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Kalaimathi B

2017-03-01

Full Text Available BACKGROUND To compare and analyse the metabolic side effects of Risperidone and Haloperidol in newly diagnosed drug-naive schizophrenic disorder patients attending Govt. Stanley Medical College Hospital during initial 6 months of therapy. MATERIALS AND METHODS Newly diagnosed drug-naïve Schizophrenic Patients (n = 60 aged between 18 - 45 years are recruited and randomly allocated into Group A (Risperidone 4 - 6 mg daily and Group B (Haloperidol 5 - 10 mg daily after getting informed consent from the patient’s family members. Patients are followed up monthly for the occurrence of metabolic abnormalities like weight gain, rise in blood pressure, elevated fasting, post-prandial blood sugar level, dyslipidaemia for a period of 6 months. RESULTS Risperidone group showed the mean body weight increase from 64.40 to 69.27, SBP/DBP increase from 123.80/79 to 129.90/83.13; FBS/PPBS increase from 100.20/129.30 to 135.40/185.00; TC increase from 177.23 to 206.23; LDL from 124.30 to 158.30; HDL 48.83 to 50.07; TG 133.47 to 197.83: Haloperidol group showed the mean body weight increase from 64.07 to 68.48, SBP/DBP increase from 123.80/79.00 to 124.27/81.67; FBS/PPBS increase from 100.20/129.30 to 119.87/167.10; TC increase from 177.23 to 197.40; LDL from 119.77 to 139.00; HDL remained 48.83; TG 133.47 to 171.40. CONCLUSION This study showed that patients in both the groups had weight gain, rise in blood sugar, LDL cholesterol and Triglycerides level, but the rise was significant in patients on Risperidone when compared to those on Haloperidol during the 6-month followup.

A comparison of risperidone and haloperidol for the risk of ischemic stroke in the elderly: a propensity score-matched cohort analysis.

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Shin, Ju-Young; Choi, Nam-Kyong; Lee, Joongyub; Park, Mi-Ju; Lee, Shin Haeng; Park, Byung-Joo

2015-08-01

With an increase in antipsychotic use in the elderly, the safety profile of antipsychotics has been emphasized. Strong concerns have been raised about whether the risk of ischemic stroke differs between risperidone and haloperidol. This study compared the risk of ischemic stroke between elderly patients taking risperidone and haloperidol. We conducted a retrospective cohort study using the Korea Health Insurance Review and Assessment Service database, applying a propensity-matched analysis. The cohort consisted of elderly patients who were newly prescribed haloperidol or risperidone between January 1, 2006 and December 31, 2009. Patients with prior cerebrovascular diseases (ICD-10, I60-I69), transient ischemic attack (ICD-10, G45), or cerebral tumors (ICD-10, C31) during 365 days prior to the initiation date were excluded. The study subjects were selected by propensity score matching. The outcome was defined as the first hospitalization for ischemic stroke (ICD-10, I63). Cox regression models were used to estimate the hazard ratio (HR) and 95% confidence intervals (95% CI) for ischemic stroke with haloperidol compared with risperidone use. A total of 14,103 patients were included in the propensity-matched cohort for each drug. Overall, the incidence rate was higher for haloperidol users compared to the risperidone users (6.43 per 1000 person-years vs. 2.88 per 1000 person-years). A substantially increased risk was observed in haloperidol users (adjusted HR = 2.02, 95% CI, 1.12-3.62). The evidence showed that haloperidol should be prescribed in the elderly with caution. © The Author(s) 2015.

Changes in electrical activity of heart during ischemic–reperfusion injury modified by the administration of antidepressants

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Vicen M.

2016-09-01

Full Text Available The aim of our work was to investigate the effect of amitriptyline, citalopram and venlafaxine on the heart during ischemic- reperfusion (l-R injury. Amitriptyline prolonged both QRS complex and QTc interval duration; citalopram and venlafaxine prolonged only QTc interval duration. Amitriptyline worked most proarrhythmogenic, citalopram least; venlafaxine increased the heart rate during ischemia; however, prolonged QTc interval at the beginning of reperfusion was followed by serious dysrhythmias.

Haloperidol differentially affects reinforcement and motivational processes in rats running an alley for intravenous heroin.

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McFarland, K; Ettenberg, A

1995-12-01

The role of drug-paired environmental stimuli in opiate self-administration was investigated by exposing animals to discrete cues that were predictive of the availability or unavailability of heroin reinforcement. Rats were trained to traverse a straight arm runway for a reinforcement consisting of a single 0.1 mg/kg intravenous infusion of heroin delivered upon entrance to the goal box. On each trial, one of two discriminative olfactory stimuli (orange and almond) was used: one which signaled the availability of heroin in the goal box (S+), and one which signaled its absence (S-). The effect of dopamine (DA) receptor antagonism on reinforcement and motivational processes was investigated by pretreating subjects with 0.0, 0.15 or 0.30 mg/kg of the DA receptor antagonist drug, haloperidol. Haloperidol had no effect on operant runway performance (i.e. goal time) in any condition. However, 24 h later, on the first post-treatment trial, those haloperidol animals that received heroin in the goal box on the previous trial (i.e. the S+ condition) ran reliably more slowly than subjects that received vehicle on the previous S+ trial. These results suggest that haloperidol does not affect the motivational properties of stimuli which predict the availability of heroin, while it does diminish the reinforcing effects of actually receiving heroin.

Differences in the time course of haloperidol-induced up-regulation of rat striatal and mesolimbic dopamine receptors

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Prosser, E.S.; Csernansky, J.G.; Hollister, L.E.

1988-01-01

Regional differences in the onset and persistence of increased dopamine D2 receptor density in rat brain were studied following daily injections of haloperidol for 3, 7, 14, or 28 days. Striatal [ 3 H]-spiroperidol Bmax values were significantly increased following 3 - 28 days of haloperidol treatment, as compared to saline controls. Olfactory tubercle Bmax values were significantly increased only after 14 or 28 days of haloperidol treatment. Nucleus accumbens Bmax values were significantly increased only in the 14-day drug treatment group, suggesting that dopamine D2 receptor up-regulation in nucleus accumbens may reverse during ongoing neuroleptic treatment. These findings suggest that important differences in adaptive responses to chronic dopamine blockade may exist between dopaminergic synapses located in various rat brain regions

Olanzapine and haloperidol for the treatment of acute symptoms of mental disorders induced by amphetamine-type stimulants: A randomized controlled trial.

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Xue, Xiaobin; Song, Yun; Yu, Xiaojie; Fan, Qiang; Tang, Jiyou; Chen, Xu

2018-02-01

This study aimed to compare olanzapine and haloperidol efficacies in the treatment of acute psychiatric symptoms due to amphetamine-type stimulants (ATSs). The Zelen II design method was used; 124 patients with acute mental disorders due to amphetamine were randomly divided into olanzapine group (n = 63) and haloperidol group (n = 61). Then, a 4-week open-label medical therapy was performed. Clinical Global Impression Scale Item 2 was employed to evaluate the onset time; meanwhile, Brief Psychiatric Rating Scale (BPRS) was used at baseline and at posttreatment weeks 1, 2, and 4. Moreover, adverse reactions during the treatment were recorded. Onset time in the olanzapine group was significantly earlier than in the haloperidol group; BPRS scores in the olanzapine group were significantly lower than haloperidol group values at 1 and 2 weeks of treatment. The overall effective rates had no statistically significant difference. Short-term olanzapine and haloperidol treatments had equivalent efficacies in the treatment of acute symptoms of mental disorders due to ATSs; however, olanzapine administration resulted in relatively earlier disease onset, with less adverse reactions.

Ciprofloxacin does not Prolong the QTc Interval : A Clinical Study in ICU Patients and Review of the Literature

NARCIS (Netherlands)

Heemskerk, Charlotte P.M.; Woldman, Evelien; Pereboom, Marieke; van der Hoeven, Ruud T M; Mantel-Teeuwisse, Aukje; Van Gemeren, Claudia; Becker, Matthijs Lambertus

2017-01-01

PURPOSE: Ciprofloxacin may prolong the QT interval and increase the risk of Torsade de Pointes (TdP). Intravenous administration of ciprofloxacin in patients with additional risks may elevate the risk of QTc interval prolongation. We prospectively assessed whether intravenous ciprofloxacin prolongs

Prevention of ICU delirium and delirium-related outcome with haloperidol: a study protocol for a multicenter randomized controlled trial

Science.gov (United States)

2013-01-01

Background Delirium is a frequent disorder in intensive care unit (ICU) patients with serious consequences. Therefore, preventive treatment for delirium may be beneficial. Worldwide, haloperidol is the first choice for pharmacological treatment of delirious patients. In daily clinical practice, a lower dose is sometimes used as prophylaxis. Some studies have shown the beneficial effects of prophylactic haloperidol on delirium incidence as well as on mortality, but evidence for effectiveness in ICU patients is limited. The primary objective of our study is to determine the effect of haloperidol prophylaxis on 28-day survival. Secondary objectives include the incidence of delirium and delirium-related outcome and the side effects of haloperidol prophylaxis. Methods This will be a multicenter three-armed randomized, double-blind, placebo-controlled, prophylactic intervention study in critically ill patients. We will include consecutive non-neurological ICU patients, aged ≥18 years with an expected ICU length of stay >1 day. To be able to demonstrate a 15% increase in 28-day survival time with a power of 80% and alpha of 0.05 in both intervention groups, a total of 2,145 patients will be randomized; 715 in each group. The anticipated mortality rate in the placebo group is 12%. The intervention groups will receive prophylactic treatment with intravenous haloperidol 1 mg/q8h or 2 mg/q8h, and patients in the control group will receive placebo (sodium chloride 0.9%), both for a maximum period of 28-days. In patients who develop delirium, study medication will be stopped and patients will subsequently receive open label treatment with a higher (therapeutic) dose of haloperidol. We will use descriptive summary statistics as well as Cox proportional hazard regression analyses, adjusted for covariates. Discussion This will be the first large-scale multicenter randomized controlled prevention study with haloperidol in ICU patients with a high risk of delirium, adequately

In vivo measurement of haloperidol affinity to dopamine D2/D3 receptors by [123I]IBZM and single photon emission computed tomography

DEFF Research Database (Denmark)

Videbaek, C; Toska, K; Friberg, L

2001-01-01

This study examines the feasibility of a steady-state bolus-integration method with the dopamine D2/D3 receptor single photon emission computer tomography (SPECT) tracer, [123I]IBZM, for determination of in vivo affinity of haloperidol. The nonspecific binding of [123I]IBZM was examined in the rat...... brain by infusion of haloperidol to plasma levels approximately 100 times the Kd level in man. In humans, Kd for haloperidol binding was measured in four healthy volunteers that were examined twice: once with partial dopamine D2/D3 receptor blockade obtained by a scheduled infusion of unlabeled...... haloperidol (0.7 mg total dosage), and once in an unblocked state. Blood sampling and SPECT were performed intermittently during 6 hours after intravenous [123I]IBZM bolus injection. Plasma [123I]IBZM was determined by octane extraction. Plasma haloperidol was determined by a radioimmunoassay, and plasma...

Pain Relief for a Presumed Accidental Use of Haloperidol: A Case Report

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Ahmet Sami Guven

2015-09-01

Full Text Available Haloperidol is a typical antipsychotic drug, that is frequently used in psychosis, Tourette syndrome and severe agitations and has anticholinergic effects and extrapyramidal signs in case of intoxication. The present paper reports a case of hemidystonia and green color vision caused by mistaken haloperidol ingestion as an analgesic agent in a 12 years old boy. Herein we would like to emphasise that the dystonia might be misdiagnosed as convulsion in emergency rooms and phonetic similarities of the brand names of the drugs may mislead the physician and cause for delay of the appropriate therapy, so to ask the family about the ingestion of drugs that are ended with "-dol" (EndolTM, indomethacine for differential diagnosis. [J Contemp Med 2015; 5(3.000: 203-205

Influence of haloperidol on the 3H-leucine incorporation in incretory organs of the mouse

International Nuclear Information System (INIS)

Lange, E.; Hackenberg, P.

1978-01-01

The 3 H-leucine incorporation in proteins of incretory organs of the mouse, the exocrine pancreas, and the renal tubuli was studied autoradiographically after administration of therapylike doses of the neuroleptic drug Haloperidol. With exception of the pancreas, a dosage dependent increase of the 3 H-leucine incorporation was observed in the treated animals. The results reveal an activation of the hypothalamus-hypophysis-adrenocortical system due to a 10-days administration of Haloperidol. These results are in conformity with former ones in brain and liver. (author)

Haloperidol Regulates the State of Phosphorylation of Ribosomal Protein S6 via Activation of PKA and Phosphorylation of DARPP-32

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Valjent, Emmanuel; Bertran-Gonzalez, Jesus; Bowling, Heather; Lopez, Sébastien; Santini, Emanuela; Matamales, Miriam; Bonito-Oliva, Alessandra; Hervé, Denis; Hoeffer, Charles; Klann, Eric; Girault, Jean-Antoine; Fisone, Gilberto

2011-01-01

Administration of typical antipsychotic drugs, such as haloperidol, promotes cAMP-dependent signaling in the medium spiny neurons (MSNs) of the striatum. In this study, we have examined the effect of haloperidol on the state of phosphorylation of the ribosomal protein S6 (rpS6), a component of the small 40S ribosomal subunit. We found that haloperidol increases the phosphorylation of rpS6 at the dual site Ser235/236, which is involved in the regulation of mRNA translation. This effect was exerted in the MSNs of the indirect pathway, which express specifically dopamine D2 receptors (D2Rs) and adenosine A2 receptors (A2ARs). The effect of haloperidol was decreased by blockade of A2ARs or by genetic attenuation of the Gαolf protein, which couples A2ARs to activation of adenylyl cyclase. Moreover, stimulation of cAMP-dependent protein kinase A (PKA) increased Ser235/236 phosphorylation in cultured striatal neurons. The ability of haloperidol to promote rpS6 phosphorylation was abolished in knock-in mice deficient for PKA activation of the protein phosphatase-1 inhibitor, dopamine- and cAMP-regulated phosphoprotein of 32 kDa. In contrast, pharmacological or genetic inactivation of p70 rpS6 kinase 1, or extracellular signal-regulated kinases did not affect haloperidol-induced rpS6 phosphorylation. These results identify PKA as a major rpS6 kinase in neuronal cells and suggest that regulation of protein synthesis through rpS6 may be a potential target of antipsychotic drugs. PMID:21814187

Efficacy and safety of valproic acid versus haloperidol in patients with acute agitation: results of a randomized, double-blind, parallel-group trial.

Science.gov (United States)

Asadollahi, Shadi; Heidari, Kamran; Hatamabadi, Hamidreza; Vafaee, Reza; Yunesian, Somayeh; Azadbakht, Alireza; Mirmohseni, Ladan

2015-05-01

The objective of this study was to compare the efficacy of valproate versus haloperidol in decreasing the agitation level in affected patients in the emergency department. We assigned 80 acutely agitated patients to receive either intravenous sodium valproate (20 mg/kg) or intramuscular haloperidol (5 mg/1 ml). Agitation was measured at baseline and 30 min after the first injection using the Agitation-Calmness Evaluation Scale (ACES), the Positive and Negative Syndrome Scale-Excited Component subscale, and the Agitated Behavior Scale. For 80 patients treated with sodium valproate, the mean ± SD dosage was 1541.5 ± 286 mg (range 940-2400). The mean postintervention ACES scores from baseline to 30 min after drug injection were 4.73 (SD = 1.93) for the valproate group and 5.45 (SD = 2.09) for the haloperidol group (P = 0.028). No significant differences were observed in terms of the mean changes 30 min after the intervention for two additional agitation scales. A larger proportion of patients in the haloperidol group experienced intense sedation (36.2%, P haloperidol in reducing agitation, with a better safety profile.

Contextual and behavioral control of antipsychotic sensitization induced by haloperidol and olanzapine

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Zhang, Chen; Li, Ming

2011-01-01

Repeated administration of haloperidol and olanzapine causes a progressively enhanced disruption of conditioned avoidance response (CAR) and a progressively enhanced inhibition of phencyclidine (PCP)-induced hyperlocomotion in rats (termed antipsychotic sensitization). Both actions are thought to reflect intrinsic antipsychotic activity. The present study examined to the extent to which antipsychotic-induced sensitization in one model (e.g. CAR) can be transferred or maintained in another (e.g. PCP hyperlocomotion) as a means of investigating the contextual and behavioral controls of antipsychotic sensitization. Well-trained male Sprague-Dawley rats were first repeatedly tested in the CAR or PCP (3.2 mg/kg, sc) hyperlocomotion model under haloperidol or olanzapine for five consecutive days. Then they were switched to the other model and tested for the expression of sensitization. Finally, all rats were switched back to the original model and retested for the expression of sensitization. Repeated haloperidol or olanzapine treatment progressively disrupted avoidance responding and decreased PCP-induced hyperlocomotion, indicating a robust sensitization. When tested in a different model, rats previously treated with haloperidol or olanzapine did not show a stronger inhibition of CAR or PCP-induced hyperlocomotion than those treated with these drugs for the first time; however, they did show such an effect when tested in the original model in which they received repeated antipsychotic treatment. These findings suggest that the expression of antipsychotic sensitization is strongly influenced by the testing environment and/or selected behavioral response under certain experimental conditions. Distinct contextual cues and behavioral responses may enter an association with unconditional drug effects via a Pavlovian conditioning process. They may also serve as occasion-setters to modulate the expression of sensitized responses. Because antipsychotic sensitization mimics

Reversal of haloperidol induced motor deficits in rats exposed to repeated immobilization stress.

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Shireen, Erum; Pervez, Sidra; Masroor, Maria; Ali, Wafa Binte; Rais, Qudsia; Khalil, Samira; Tariq, Anum; Haleem, Darakshan Jabeen

2014-09-01

Stress is defined as a non specific response of body to any physiological and psychological demand. Preclinical studies have shown that an uncontrollable stress condition produces neurochemical and behavioral deficits. The present study was conducted to test the hypothesis that a decrease in the responsiveness of somatodendritic 5-hydroxytryptamine (5-HT)-1A receptors following adaptation to stress could attenuate haloperidol induced acute parkinsonian like effect. Results showed that single exposure (2h) to immobilization stress markedly decreased food intake, growth rate and locomotor activity but these stress-induced behavioral deficits were not observed following repeated (2h/day for 5 days) exposure of immobilization stress suggesting behavioral tolerance occurs to similar stress. An important finding of present study is a reversal of haloperidol-induced motor deficits in animals exposed to repeated immobilization stress than respective control animals. It is suggested that stress induced possible desensitization of somatodendritic 5-HT-1A as well as 5-HT-2C receptors could release dopamine system from the inhibitory influence of serotonin. On the other hand, an increase in the effectiveness of postsynaptic 5-HT-1A receptors elicits a direct stimulatory influence on the activity of dopaminergic neuron and is possibly involved in the reversal of haloperidol-induced parkinsonian like symptoms in repeatedly immobilized rats.

Influence of haloperidol on the /sup 3/H-leucine incorporation in incretory organs of the mouse

Energy Technology Data Exchange (ETDEWEB)

Lange, E; Hackenberg, P [Bezirksnervenklinik, Schwerin (German Democratic Republic)

1978-01-01

The /sup 3/H-leucine incorporation in proteins of incretory organs of the mouse, the exocrine pancreas, and the renal tubuli was studied autoradiographically after administration of therapylike doses of the neuroleptic drug Haloperidol. With exception of the pancreas, a dosage dependent increase of the /sup 3/H-leucine incorporation was observed in the treated animals. The results reveal an activation of the hypothalamus-hypophysis-adrenocortical system due to a 10-days administration of Haloperidol. These results are in conformity with former ones in brain and liver.

Haloperidol-induced striatal Nur77 expression in a non-human primate model of tardive dyskinesia

Science.gov (United States)

Mahmoudi, Souha; Blanchet, Pierre J.; Lévesque, Daniel

2015-01-01

Tardive dyskinesia (TD) is a delayed and potentially irreversible motor complication arising in patients chronically exposed to antipsychotic drugs. As several modern (so-called atypical) antipsychotic drugs are common offenders, the widening clinical indications for prescription as well as exposure of vulnerable individuals, TD will remain a significant drug-induced unwanted side effect. In addition, the pathophysiology of TD remains elusive and therapeutics difficult. Based on rodent experiments, we have previously shown that the transcriptional factor Nur77 (also known as NGFI-B or Nr4a1) is induced in the striatum following antipsychotic drug exposure as part of a long-term neuroadaptive process. To confirm this, we exposed adult capuchin (Cebus apella) monkeys to prolonged treatments with haloperidol (median 18.5 months, N=11) or clozapine (median 6 months, N=6). Six untreated animals were used as controls. Six haloperidol-treated animals developed mild TD movements similar to those found in humans. No TD was observed in the clozapine group. Postmortem analysis of Nur77 expression measured by in situ hybridization revealed a stark contrast between the two drugs, as Nur77 mRNA levels in the caudate-putamen were strongly upregulated in animals exposed to haloperidol while spared following clozapine treatment. Interestingly, within the haloperidol-treated group, TD-free animals showed higher Nur77 expression in putamen subterritories compared to dyskinetic animals. This suggests that Nur77 expression might be associated with a reduced risk to TD in this experimental model and could provide a novel target for drug intervention. PMID:23551242

The α2C-adrenoceptor antagonist, ORM-10921, has antipsychotic-like effects in social isolation reared rats and bolsters the response to haloperidol.

Science.gov (United States)

Uys, Madeleine; Shahid, Mohammed; Sallinen, Jukka; Dreyer, Walter; Cockeran, Marike; Harvey, Brian H

2016-11-03

Early studies suggest that selective α2C-adrenoceptor (AR)-antagonism has anti-psychotic-like and pro-cognitive properties. However, this has not been demonstrated in an animal model of schizophrenia with a neurodevelopmental construct. The beneficial effects of clozapine in refractory schizophrenia and associated cognitive deficits have, among others, been associated with its α2C-AR modulating activity. Altered brain-derived neurotrophic factor (BDNF) has been linked to schizophrenia and cognitive deficits. We investigated whether the α2C-AR antagonist, ORM-10921, could modulate sensorimotor gating and cognitive deficits, as well as alter striatal BDNF levels in the social isolation reared (SIR) model of schizophrenia, comparing its effects to clozapine and the typical antipsychotic, haloperidol, the latter being devoid of α2C-AR-activity. Moreover, the ability of ORM-10921 to augment the effects of haloperidol on the above parameters was also investigated. Animals received subcutaneous injection of either ORM-10921 (0.01mg/kg), clozapine (5mg/kg), haloperidol (0.2mg/kg), haloperidol (0.2mg/kg)+ORM-10921 (0.01mg/kg) or vehicle once daily for 14days, followed by assessment of novel object recognition (NOR), prepulse inhibition (PPI) of startle response and striatal BDNF levels. SIR significantly attenuated NOR memory as well as PPI, and reduced striatal BDNF levels vs. social controls. Clozapine, ORM-10921 and haloperidol+ORM-10921, but not haloperidol alone, significantly improved SIR-associated deficits in PPI and NOR, with ORM-10921 also significantly improving PPI deficits vs. haloperidol-treated SIR animals. Haloperidol+ORM-10921 significantly reversed reduced striatal BDNF levels in SIR rats. α2C-AR-antagonism improves deficits in cognition and sensorimotor gating in a neurodevelopmental animal model of schizophrenia and bolsters the effects of a typical antipsychotic, supporting a therapeutic role for α2C-AR-antagonism in schizophrenia. Copyright �

Genotyping and phenotyping of CYP2D6 and CYP3A isoenzymes in patients with alcohol use disorder: correlation with haloperidol plasma concentration.

Science.gov (United States)

Sychev, Dmitry A; Zastrozhin, Mikhail S; Miroshnichenko, Igor I; Baymeeva, Natalia V; Smirnov, Valery V; Grishina, Elena A; Ryzhikova, Kristina A; Mirzaev, Karin B; Markov, Dmitry D; Skryabin, Valentin Y; Snalina, Nataliya E; Nosikova, Polina G; Savchenko, Ludmila M; Bryun, Evgeny A

2017-09-26

Haloperidol is used for the treatment of alcohol use disorders in patients with signs of alcohol-related psychosis. Haloperidol therapy poses a high risk of adverse drug reactions (ADR). Contradictory data, which include the effects of genetic polymorphisms in genes encoding the elements of haloperidol biotransformation system on haloperidol metabolism rate and plasma drug concentration ratio, are described in patients with different genotypes. The primary objective of this study was to investigate the effects of CYP2D6 and CYP3A5 genetic polymorphisms on haloperidol equilibrium concentration in patients with alcohol use disorder. The study included 69 male patients with alcohol use disorder. Genotyping was performed using the allele-specific real-time PCR. CYP2D6 and CYP3A were phenotyped with HPLC-MS using the concentration of endogenous substrate of the enzyme and its urinary metabolites [6-hydroxy-1,2,3,4-tetrahydro-β-carboline(6-HO-THBC) to pinoline ratio for CYP2D6 and 6-β-hydroxycortisol to cortisol ratio for CYP3A]. The equilibrium plasma concentration was determined using LC-MS-MS. Results indicated that both C/D indexes and equilibrium concentration levels depend on CYP2D6 genetic polymorphism, but only in patients receiving haloperidol intramuscular injections [0.26 (0.09; 0.48) vs. 0.54 (0.44; 0.74), p=0.037]. The study demonstrates that CYP2D6 genetic polymorphism (1846G>A) can affect haloperidol concentration levels in patients with alcohol use disorder.

Comparison of haloperidol and midazolam in restless management of patients referred to the Emergency Department: A double-blinded, randomized clinical trial

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Mehrdad Esmailian

2015-01-01

Full Text Available Background: Restless and violent behaviors are common in Emergency Departments (EDs, which need therapeutic interventions in most of the times. The first-generation anti-psychotic drugs are one of the most applicable therapeutic agents in the management of such patients, but their use has some limitations. Some studies suggest midazolam as an alternative medicine. Therefore, this study was performed with the aim of comparison of the efficacy and safety of haloperidol and midazolam in the restless management of referring patients to EDs. Materials and Methods: The present double-blinded trial was done on patients needed sedation and referred to the ED of Alzahra Hospital, Isfahan, Iran, in 2014. The patients were categorized into two random groups of haloperidol (5 mg and midazolam receivers (2.5 mg for those weighing 50 kg, as intramuscular administration. The time to achieve sedation, need for rescue dose, need to resedation within the first 60 min, and adverse effects of drugs were compared among the groups. Results: Forty-eight patients were entered to the study. The mean age in the haloperidol and midazolam groups was 44.8 ± 4.1 years and 45.5 ± 4.7 years, respectively (P = 0.91. The mean time of sedation in the haloperidol and midazolam groups was 5.6 ± 0.3 min and 5.2 ± 0.1 min, respectively (P = 0.31. The mean time of full consciousness after sedation was 36.2 ± 4.5 min and 38.2 ± 3.4 min in the haloperidol and midazolam groups, respectively (P = 0.72. On average, time to arousal in the midazolam group was 10.33 min more than the haloperidol group, but it was not statistically significant. Conclusion: The results of the present study show that administration of midazolam and haloperidol have similar efficacy in the treatment of restless symptoms with the same recovery time from drug effects for referring patients to the ED. In addition, none of the adverse effects were observed in this study.

A randomized, placebo-controlled, four-period crossover, definitive QT study of the effects of APF530 exposure, high-dose intravenous granisetron, and moxifloxacin on QTc prolongation

International Nuclear Information System (INIS)

Mason, Jay W; Moon, Thomas E; O’Boyle, Erin; Dietz, Albert

2014-01-01

Regulatory concern about potential QT-interval prolongation by serotonin-receptor antagonist antiemetics prompted product-label changes. The first-generation serotonin-receptor antagonist granisetron is available in oral (PO), intravenous (IV), and transdermal formulations. APF530 is a formulation that provides sustained release of granisetron when administered as a single subcutaneous (SC) injection. The Phase I study reported here evaluated effects of APF530 on electrocardiographic intervals. This single-site, double-blind, placebo-controlled, four-period crossover trial randomized healthy men and women to receive varying sequences of APF530 1 g SC, granisetron 50 μg/kg IV, moxifloxacin 400 mg PO, and placebo. Subjects were assessed for 49 hours after each treatment. The primary objective was to evaluate differences between baseline-adjusted, heart rate-corrected QT-interval change using the Fridericia rate correction (dQTcF) for APF530 1 g SC and placebo. Electrocardiograms were performed at various times throughout the assessment period. Pharmacokinetics and safety were evaluated. The upper one-sided 95% confidence interval (CI) for mean baseline-adjusted dQTcF at each post-dose time point between APF530 and placebo excluded 10 ms, indicating that APF530 1 g SC had no clinically significant effect on QTcF. Maximum observed QTcF change was 4.15 ms (90% CI, 0.94 to 7.36) at Hour 3. No clinically significant changes in other electrocardiogram intervals were observed. APF530 SC pharmacokinetics were as expected, with slow absorption (maximum plasma concentration 35.8 ng/mL, median time to maximum plasma concentration 11.1 hours) and slow elimination (mean half-life 18.6 hours; systemic clearance 20.2 L/hour) of granisetron versus the expected early peak concentration and elimination of granisetron IV. APF530 SC was well tolerated. Adverse events, most commonly constipation and SC injection-site reactions, were generally mild and quickly resolved. APF530 1 g SC did

Effects of the Antipsychotic Drug, Haloperidol, on Reproduction in the Fathead Minnow

Science.gov (United States)

Haloperidol is a butyrophenone antipsychotic drug used for the treatment of human hyperactive and manic disorders, agitation, and schizophrenia. The drug is thought to act through antagonism of dopaminergic receptors. We have studied a variety of endocrine-disrupting chemicals wi...

Low proarrhythmic potential of citalopram and escitalopram in contrast to haloperidol in an experimental whole-heart model.

Science.gov (United States)

Frommeyer, Gerrit; Brücher, Benedict; von der Ahe, Henning; Kaese, Sven; Dechering, Dirk G; Kochhäuser, Simon; Bogossian, Harilaos; Milberg, Peter; Eckardt, Lars

2016-10-05

In several case reports proarrhythmic effects of citalopram and escitalopram have been reported. Systematic analyses on prorarrhythmic effects of these drugs are not yet available. The aim of the present study was to investigate if application of citalopram, escitalopram or haloperidol provokes polymorphic ventricular tachycardia in a sensitive model of proarrhythmia. In isolated rabbit hearts monophasic action potentials and ECG showed a significant QT-prolongation after application of citalopram (2µM: +47ms, 4µM: +56ms, Pescitalopram also increased QT-interval (2µM: +3ms, 4µM: +30ms, Pescitalopram demonstrated a rather safe electrophysiologic profile despite significant QT prolongation. In contrast, haloperidol led to significant increase of dispersion of repolarization while this parameter remained stable under the influence of citalopram or escitalopram. These results imply that application of citalopram or escitalopram is not as proarrhythmic as some case reports might suggest while haloperidol is torsadogenic. Copyright © 2016 Elsevier B.V. All rights reserved.

Qtc interval as a guide to select those patients with congestive heart failure and reduced left ventricular systolic function who will benefit from antiarrhythmic treatment with dofetilide

DEFF Research Database (Denmark)

Brendorp, B; Elming, H; Jun, L

2001-01-01

BACKGROUND: A prolonged QTc interval is considered a contraindication for class III antiarrhythmic drugs, but the influence of a normal or a slightly increased baseline QTc interval on the risk or benefit of treatment with a class III antiarrhythmic drug is not sufficiently clarified. METHODS...... limits is associated with a marked reduction of mortality in patients with CHF and left ventricular systolic dysfunction treated with dofetilide. This is a potentially important indication of which patients with CHF might benefit from prophylactic treatment with an antiarrhythmic drug....

Covariate analysis of QTc and T-wave morphology: new possibilities in the evaluation of drugs that affect cardiac repolarization

DEFF Research Database (Denmark)

Graff, Claus; Struijk, Johannes J.; Matz, J

2010-01-01

This study adds the dimension of a T-wave morphology composite score (MCS) to the QTc interval-based evaluation of drugs that affect cardiac repolarization. Electrocardiographic recordings from 62 subjects on placebo and 400 mg moxifloxacin were compared with those from 21 subjects on 160 and 320...

Impact of lithium alone or in combination with haloperidol on oxidative stress parameters and cell viability in SH-SY5Y cell culture.

Science.gov (United States)

Gawlik-Kotelnicka, Oliwia; Mielicki, Wojciech; Rabe-Jabłońska, Jolanta; Lazarek, Jerry; Strzelecki, Dominik

2016-02-01

It has been reported that lithium may inhibit lipid peroxidation and protein oxidation. Lithium salts also appear to stimulate cell proliferation, increase neurogenesis, and delay cell death. Oxidative stress and neurodegeneration may play an important role in the pathophysiology of bipolar disorder and the disease course thereof. The aim of this research is to estimate the influence of lithium (alone and in combination with haloperidol) on the parameters of oxidative stress and viability of SH-SY5Y cell lines in neutral and pro-oxidative conditions. The evaluated oxidative stress parameter was lipid peroxidation. The viability of the cell lines was measured utilising the MTT test. In neutral conditions, higher levels of thiobarbituric acid reactive substances were observed in those samples which contained both haloperidol and lithium than in other samples. However, these differences were not statistically significant. Cell viability was significantly higher in therapeutic lithium samples than in the controls; samples of haloperidol alone as well as those of haloperidol with lithium did not differ from controls. The results of our study may indicate that lithium possess neuroprotective properties that may be partly due to antioxidative effects. The combination of lithium and haloperidol may generate increased oxidative stress.

Development of [11C]-α-aminoisobutyric acid and [18F]-haloperidol as substrate-specific radiotracers

International Nuclear Information System (INIS)

Zanzonico, P.B.

1982-01-01

In light of the emergence of positron emission tomography (PET), two new substrate-specific radiotracers have been synthesized and evaluated as potential agents for the study of specific physiological processes: [1- 11 C]-α-aminoisobutyric acid ([1- 11 C]-AIB), a transport system-specific radiotracer for tumor localization and for the assessment of amino acid transport in vivo; and [ 18 F]-haloperidoll, a receptor-binding radiotracer for the assessment of brain dopamine receptors in vivo. AIB, a non-metabolized amino acid, accumulates in cells, particularly malignant cells, via the A type, or ''alanine-preferring'', amino acid transport system [1- 11 C]-AIB in normal and in treated and untreated tumor-bearing rats, in tumor-bearing dogs, and in a tumor-bearing patient indicate rapid blood clearance and, concomitantly, rapid tissue localization, with slow net redistribution. Generally, there was selective localization in the kidney, in the liver, and in the pancreas, as well as in various tumors. The canine tumors and the human tumor were well visualized by external scintigraphy, especially when utilizing PET. [ 18 F]-Haloperidol, a dopamine receptor-binding neuroleptic of the butyrophenone series widely used in the management of schizophrenia was prepared via the Balz-Schiemann reaction. As the haloperdol dose administered to mice was increased from 0.01 to 1000 μg/kg, the relative concentration (μCi found per gm tisue sample/μCi injected per gm body mass) of [ 18 F]-haloperidol at 1 hr decreased from 30 to 1.0 in the striatum and from 8.0 to 1.0 in the cerebellum. The decrease in striatum radioactivity reflects competition between labeled and unlabeled haloperidol for dopamine receptors

Amisulpride plus valproate vs haloperidol plus valproate in the treatment of acute mania of bipolar I patients: a multicenter, open-label, randomized, comparative trial

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Pierre Thomas

2008-06-01

Full Text Available Pierre Thomas1, Eduard Vieta2 for the SOLMANIA study group1Department of Psychiatry, Fontan Hospital CHRU Lille, University of Lille 2, France; 2Bipolar Disorders Program, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, SpainAbstract: The primary objective of this study was to compare the effectiveness of combination treatment of valproate and amisulpride with that of valproate and haloperidol in bipolar I disorder. Adult inpatients with a current manic episode fulfilling DSM-IV-TR diagnostic criteria for bipolar type I disorder were included. Patients were randomized to amisulpride (400–800 mg/day or haloperidol (5–15 mg/day for 3 months and all received valproate. The primary effectiveness criterion was the percentage of responders (defined by a decrease of ≥50% of the Y-MRS in patients completing the study. Safety was evaluated by adverse event reporting, determination of extrapyramidal function and clinical examination. Sixty-two patients were randomized to receive valproate-amisulpride, and 61 to receive valproate-haloperidol. At study end, responder rates were 72.6% in the amisulpride group and 65.5% in the haloperidol group. Remission rates were 83.9% and 89.7%, respectively. At study end, neither response rates nor remission rates differed significantly between groups. Treatment-emergent adverse events occurred significantly (p = 0.009 more frequently in the haloperidol group (86.4% than in the amisulpride group (66.1%. In conclusion, the valproate–amisulpride combination was as effective as the valproate – haloperidol combination in bipolar I patients, with a better safety profile.Keywords: amisulpride, valproate, haloperidol, clinical trial, mania, bipolar disorder

Effectiveness of clozapine, haloperidol and chlorpromazine in schizophrenia during a five-year period Eficácia da clozapina, haloperidol e clorpromazina na esquizofrenia em um período de cinco anos

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Dragan B. Ravanic

2009-06-01

Full Text Available OBJECTIVE: The aim of our study was to evaluate the effects of low doses of clozapine in flexible regime in comparison with haloperidol and chlorpromazine in long term. METHOD: The naturalistic study was prospective, active-controlled with 325 adult outpatients of both genders (140 females, with mean year age of 34.8 (range 21-57, suffering from chronic schizophrenia. The first onset of illness was at the mean of 27.9 years (range 17-38, and subjects had the mean year age of 4.1±0.5 previous relapses. The patients were allocated to receive haloperidol (105 subjects, dose range 2-15 mg, chlorpromazine (n=105, 100-400 mg or clozapine (n=115, 75-600 mg. The scores of psychometric instruments (GWB, PANSS, CGI were regularly assessed during 5 year period. RESULTS: The sixty-six responders were included in per-protocol analysis: 12, 10 and 16 with positive and 7, 6 and 15 with negative schizophrenic syndrome in haloperidol, chlorpromazine and clozapine group, respectively. The statistically significant differences in all psychometric scores was found, for both schizophrenic syndromes, favoring clozapine. The distribution of eighteen different types of adverse events, which we noted, were significantly different among treatment groups ( χ2=315.7, df=34, pOBJETIVO: O propósito deste estudo foi avaliar os efeitos de baixas doses de clozapina em regime flexível comparando com o uso de haloperidol e clorpromazina por período de 5 anos. MÉTODO: Um estudo prospectivo naturalístico, ativo-controlado foi realizado com 325 pacientes com idade média de 34,8 (variância 21-57. Todos com diagnóstico de esquizofrenia. No primeiro surto da doença os pacientes apresentavam idade média de 27,9 anos (variância 17-38 e os surtos subsequentes apareceram em média 4,1±0,5 anos após. Os pacientes foram orientados a receberem haloperidol (105 pacientes com dose entre 2 e 15 mg, clorpromazina (105 pacientes com dose entre 100 e 400 mg e clozapina (115 pacientes

Preliminary studies with [18F]haloperidol: a radioligand for in vivo studies of the dopamine receptors

International Nuclear Information System (INIS)

Tewson, T.J.; Raichle, M.E.; Welch, M.J.

1980-01-01

The authors report a synthesis of [ 18 F]haloperidol of sufficiently high specific activity to permit the mapping of dopamine receptors in vivo in man using PET. The preliminary work with this radioligand in vivo in monkeys clearly suggests that haloperidol enters brain from blood by means of carrier-mediated, facilitated diffusion rather than simple diffusion. This rather surprising observation not only assumes special importance in the interpretation of in vivo pharmacokinetic data on dopamine receptors in man or animals but may also be important in considerations of the possible mode of action of this drug on the central nervous system. (Auth.)

Aripiprazole and Haloperidol Activate GSK3β-Dependent Signalling Pathway Differentially in Various Brain Regions of Rats.

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Pan, Bo; Huang, Xu-Feng; Deng, Chao

2016-03-28

Aripiprazole, a dopamine D₂ receptor (D₂R) partial agonist, possesses a unique clinical profile. Glycogen synthase kinase 3β (GSK3β)-dependent signalling pathways have been implicated in the pathophysiology of schizophrenia and antipsychotic drug actions. The present study examined whether aripiprazole differentially affects the GSK3β-dependent signalling pathways in the prefrontal cortex (PFC), nucleus accumbens (NAc), and caudate putamen (CPu), in comparison with haloperidol (a D₂R antagonist) and bifeprunox (a D₂R partial agonist). Rats were orally administrated aripiprazole (0.75 mg/kg), bifeprunox (0.8 mg/kg), haloperidol (0.1 mg/kg) or vehicle three times per day for one week. The levels of protein kinase B (Akt), p-Akt, GSK3β, p-GSK3β, dishevelled (Dvl)-3, and β-catenin were measured by Western Blots. Aripiprazole increased GSK3β phosphorylation in the PFC and NAc, respectively, while haloperidol elevated it in the NAc only. However, Akt activity was not changed by any of these drugs. Additionally, both aripiprazole and haloperidol, but not bifeprunox, increased the expression of Dvl-3 and β-catenin in the NAc. The present study suggests that activation of GSK3β phosphorylation in the PFC and NAc may be involved in the clinical profile of aripiprazole; additionally, aripiprazole can increase GSK3β phosphorylation via the Dvl-GSK3β-β-catenin signalling pathway in the NAc, probably due to its relatively low intrinsic activity at D₂Rs.

A randomized, placebo-controlled, four-period crossover, definitive QT study of the effects of APF530 exposure, high-dose intravenous granisetron, and moxifloxacin on QTc prolongation

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Mason JW

2014-03-01

Full Text Available Jay W Mason,1 Thomas E Moon,2 Erin O’Boyle,3 Albert Dietz41Department of Medicine, University of Utah, Salt Lake City, UT, 2Tarizona eHealth Services, Inc., San Carlos, CA, 3AP Pharma, Redwood City, CA, 4Spaulding Clinical Research, West Bend, WI, USABackground: Regulatory concern about potential QT-interval prolongation by serotonin-receptor antagonist antiemetics prompted product-label changes. The first-generation serotonin-receptor antagonist granisetron is available in oral (PO, intravenous (IV, and transdermal formulations. APF530 is a formulation that provides sustained release of granisetron when administered as a single subcutaneous (SC injection. The Phase I study reported here evaluated effects of APF530 on electrocardiographic intervals.Methods: This single-site, double-blind, placebo-controlled, four-period crossover trial randomized healthy men and women to receive varying sequences of APF530 1 g SC, granisetron 50 μg/kg IV, moxifloxacin 400 mg PO, and placebo. Subjects were assessed for 49 hours after each treatment. The primary objective was to evaluate differences between baseline-adjusted, heart rate-corrected QT-interval change using the Fridericia rate correction (dQTcF for APF530 1 g SC and placebo. Electrocardiograms were performed at various times throughout the assessment period. Pharmacokinetics and safety were evaluated.Results: The upper one-sided 95% confidence interval (CI for mean baseline-adjusted dQTcF at each post-dose time point between APF530 and placebo excluded 10 ms, indicating that APF530 1 g SC had no clinically significant effect on QTcF. Maximum observed QTcF change was 4.15 ms (90% CI, 0.94 to 7.36 at Hour 3. No clinically significant changes in other electrocardiogram intervals were observed. APF530 SC pharmacokinetics were as expected, with slow absorption (maximum plasma concentration 35.8 ng/mL, median time to maximum plasma concentration 11.1 hours and slow elimination (mean half-life 18.6 hours

A Pharmacogenetic Discovery: Cystamine Protects Against Haloperidol-Induced Toxicity and Ischemic Brain Injury.

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Zhang, Haili; Zheng, Ming; Wu, Manhong; Xu, Dan; Nishimura, Toshihiko; Nishimura, Yuki; Giffard, Rona; Xiong, Xiaoxing; Xu, Li Jun; Clark, J David; Sahbaie, Peyman; Dill, David L; Peltz, Gary

2016-05-01

Haloperidol is an effective antipsychotic agent, but it causes Parkinsonian-like extrapyramidal symptoms in the majority of treated subjects. To address this treatment-limiting toxicity, we analyzed a murine genetic model of haloperidol-induced toxicity (HIT). Analysis of a panel of consomic strains indicated that a genetic factor on chromosome 10 had a significant effect on susceptibility to HIT. We analyzed a whole-genome SNP database to identify allelic variants that were uniquely present on chromosome 10 in the strain that was previously shown to exhibit the highest level of susceptibility to HIT. This analysis implicated allelic variation within pantetheinase genes (Vnn1 and Vnn3), which we propose impaired the biosynthesis of cysteamine, could affect susceptibility to HIT. We demonstrate that administration of cystamine, which is rapidly metabolized to cysteamine, could completely prevent HIT in the murine model. Many of the haloperidol-induced gene expression changes in the striatum of the susceptible strain were reversed by cystamine coadministration. Since cystamine administration has previously been shown to have other neuroprotective actions, we investigated whether cystamine administration could have a broader neuroprotective effect. Cystamine administration caused a 23% reduction in infarct volume after experimentally induced cerebral ischemia. Characterization of this novel pharmacogenetic factor for HIT has identified a new approach for preventing the treatment-limiting toxicity of an antipsychotic agent, which could also be used to reduce the extent of brain damage after stroke. Copyright © 2016 by the Genetics Society of America.

Frequency of Extrapyramidal Adverse Reactions in Schizophrenic Outpatients Treated with Risperidone, Olanzapine, Quetiapine or Haloperidol : Results of the EIRE Study.

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Bobes, Julio; Rejas, J; Garcia-Garcia, M; Rico-Villademoros, F; García-Portilla, M P; Madrigal, M; Hernández, G

2002-09-01

The EIRE (Estudio de Investigaciön de Resultados en Esquizofrenia - Outcomes Research Study in Schizophrenia) study was initiated in order to assess the frequency of adverse reactions [extrapyramidal symptoms (EPS), hyperprolactinaemia, sexual dysfunction and weight gain] caused by atypical antipsychotics and haloperidol in patients with schizophrenia during routine treatment in clinical practice. This paper presents the results of the assessment of extrapyramidal adverse reactions. Outpatients diagnosed with schizophrenia according to the Diagnostic and Statistical Manual of mental disorders, 4th edition (DSM-IV), criteria and receiving a single antipsychotic (risperidone, olanzapine, quetiapine or haloperidol) for at least 4 weeks were consecutively recruited. In this cross-sectional and non-interventional study data were collected in a single visit; this included demographic and clinical characteristics, current antipsychotic and concomitant treatment, and data on several adverse effects listed in a modified version of the UKU (Udvalg for Kliniske Undersogelser - Committee on Clinical Investigations) scale. For paired comparisons of the frequency of adverse reactions between treatments the Chi-squared (χ 2 ) test was used. For estimation of the risk of a given adverse reaction with a given treatment a logistic regression method was used. 636 evaluable patients (of 669 recruited) were assessed. The frequency of EPS with haloperidol (78.3% of the cases) was higher than with risperidone (55.1%), quetiapine (39.5%) and olanzapine (35.8%) [χ 2 : p < 0.05], and the difference between risperidone and olanzapine was also statistically significant (χ 2 : p < 0.05). Very similar results were obtained in the individualised analysis of the items as regards the occurrence of akathisia, which was also more frequent in the haloperidol (36.8%) and risperidone (19.7%) groups than in the olanzapine (11.4%) and quetiapine (2.6%) groups (χ 2 : p < 0.05). Olanzapine, quetiapine

Oxycodone is associated with dose-dependent QTc prolongation in patients and low-affinity inhibiting of hERG activity in vitro

DEFF Research Database (Denmark)

Fanoe, Søren; Jensen, Gorm Boje; Sjøgren, Per

2008-01-01

with the use of these drugs. WHAT THIS PAPER ADDS: This study is the first to show that oxycodone dose is associated with QT prolongation and in vitro blockade of hERG channels expressed in HEK293. Neither morphine nor tramadol doses are associated with the QT interval length. AIMS: During recent years some...... and TdP could be a more general problem associated with the use of these drugs. The aims of this study were to evaluate the association between different opioids and the QTc among patients and measure hERG activity under influence by opioids in vitro. METHODS: One hundred chronic nonmalignant pain...... patients treated with methadone, oxycodone, morphine or tramadol were recruited in a cross-sectional study. The QTc was estimated from a 12-lead ECG. To examine hERG activity in the presence of oxycodone, electrophysiological testing was conducted using Xenopus laevis oocytes and HEK293 cells expressing h...

Disruption of dopamine D1/D2 receptor complex is involved in the function of haloperidol in cardiac H9c2 cells.

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Lencesova, L; Szadvari, I; Babula, P; Kubickova, J; Chovancova, B; Lopusna, K; Rezuchova, I; Novakova, Z; Krizanova, O; Novakova, M

2017-12-15

Haloperidol is an antipsychotic agent and acts as dopamine D2 receptor (D2R) antagonist, as a prototypical ligand of sigma1 receptors (Sig1R) and it increases expression of type 1 IP 3 receptors (IP 3 R1). However, precise mechanism of haloperidol action on cardiomyocytes through dopaminergic signaling was not described yet. This study investigated a role of dopamine receptors in haloperidol-induced increase in IP 3 R1 and Sig1R, and compared physiological effect of melperone and haloperidol on basic heart parameters in rats. We used differentiated NG-108 cells and H9c2 cells. Gene expression, Western blot and immunofluorescence were used to evaluate haloperidol-induced differences; proximity ligation assay (PLA) and immunoprecipitation to determine interactions of D1/D2 receptors. To evaluate cardiac parameters, Wistar albino male rats were used. We have shown that antagonism of D2R with either haloperidol or melperone results in upregulation of both, IP 3 R1 and Sig1R, which is associated with increased D2R, but reduced D1R expression. Immunofluorescence, immunoprecipitation and PLA support formation of heteromeric D1/D2 complexes in H9c2 cells. Treatment with haloperidol (but not melperone) caused decrease in systolic and diastolic blood pressure and significant increase in heart rate. Because D1R/D2R complexes can engage Gq-like signaling in other experimental systems, these results are consistent with the possibility that disruption of D1R/D2R complex in H9c2 cells might cause a decrease in IP 3 R1 activity, which in turn may account for the increase expression of IP 3 R and Sig1R. D2R is probably not responsible for changes in cardiac parameters, since melperone did not have any effect. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Dopamine dynamics during emotional cognitive processing: Implications of the specific actions of clozapine compared with haloperidol.

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Kawano, Masahiko; Oshibuchi, Hidehiro; Kawano, Takaaki; Muraoka, Hiroyuki; Tsutsumi, Takahiro; Yamada, Makiko; Inada, Ken; Ishigooka, Jun

2016-06-15

Clozapine has improved efficacy relative to typical antipsychotics in schizophrenia treatment, particularly regarding emotional symptoms. However, the mechanisms underlying its therapeutic benefits remain unclear. Using a methamphetamine-sensitised rat model, we measured changes in dopamine levels in the amygdalae in response to a fear-conditioned cue, serving as a biochemical marker of emotional cognitive processing disruption in psychosis, for analysing the biochemical mechanisms associated with the clinical benefits of clozapine. We also compared how clozapine and haloperidol affected basal dopamine levels and phasic dopamine release in response to the fear-conditioned cue. Extracellular dopamine was collected from the amygdalae of freely moving rats via microdialysis and was analysed by high-performance liquid chromatography. Clozapine or haloperidol was injected during microdialysis, followed by exposure to the fear-conditioned cue. We analysed the ratio of change in dopamine levels from baseline. Haloperidol treatment increased the baseline dopamine levels in both non-sensitised and sensitised rats. Conversely, clozapine only increased the basal dopamine levels in the non-sensitised rats, but not in the sensitised rats. Although both antipsychotics attenuated phasic dopamine release in both the non-sensitised and sensitised rats, the attenuation extent was greater for clozapine than for haloperidol under both dopaminergic conditions. Our findings indicate that stabilized dopamine release in the amygdalae is a common therapeutic mechanism of antipsychotic action during emotional processing. However, the specific dopaminergic state-dependent action of clozapine on both basal dopamine levels and stress-induced dopamine release may be the underlying mechanism for its superior clinical effect on emotional cognitive processing in patients with schizophrenia. Copyright © 2016 Elsevier B.V. All rights reserved.

Bilateral Dislocation of Temporomandibular Joint Induced by Haloperidol Following Suicide Attempt: A Case Report

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Mosa Arghand Dargahi

2012-03-01

Full Text Available Drug induced dystonic reactions are among common presentations of patients in emergency departments, and typically occur with antidopaminergic agents as their extra-pyramidal side effects. Dystonic reactions usually occur within the first few hours or days after commencing a drug or dose increase. Unlike other extra-pyramidal side effects, a patient may experience acute dystonic reactions (ADRs with the administration of just a single dose. Oromandibular dystonia is a subtype of dystonia which can present with perioral manifestations. In extreme cases, it can lead to temporomandibular dislocation. Haloperidol, as a high potent typical antipsychotic drug, can induce dystonia with blocking D2 dopamine receptors. The present paper reports a case of bilateral dislocation of temporomandibular joint following ingestion of haloperidol in a suicidal attempt in a 17 years old girl.

Effects of aripiprazole and haloperidol on neural activation during a simple motor task in healthy individuals: A functional MRI study.

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Goozee, Rhianna; O'Daly, Owen; Handley, Rowena; Reis Marques, Tiago; Taylor, Heather; McQueen, Grant; Hubbard, Kathryn; Pariante, Carmine; Mondelli, Valeria; Reinders, Antje A T S; Dazzan, Paola

2017-04-01

The dopaminergic system plays a key role in motor function and motor abnormalities have been shown to be a specific feature of psychosis. Due to their dopaminergic action, antipsychotic drugs may be expected to modulate motor function, but the precise effects of these drugs on motor function remain unclear. We carried out a within-subject, double-blind, randomized study of the effects of aripiprazole, haloperidol and placebo on motor function in 20 healthy men. For each condition, motor performance on an auditory-paced task was investigated. We entered maps of neural activation into a random effects general linear regression model to investigate motor function main effects. Whole-brain imaging revealed a significant treatment effect in a distributed network encompassing posterior orbitofrontal/anterior insula cortices, and the inferior temporal and postcentral gyri. Post-hoc comparison of treatments showed neural activation after aripiprazole did not differ significantly from placebo in either voxel-wise or region of interest analyses, with the results above driven primarily by haloperidol. We also observed a simple main effect of haloperidol compared with placebo, with increased task-related recruitment of posterior cingulate and precentral gyri. Furthermore, region of interest analyses revealed greater activation following haloperidol compared with placebo in the precentral and post-central gyri, and the putamen. These diverse modifications in cortical motor activation may relate to the different pharmacological profiles of haloperidol and aripiprazole, although the specific mechanisms underlying these differences remain unclear. Evaluating healthy individuals can allow investigation of the effects of different antipsychotics on cortical activation, independently of either disease-related pathology or previous treatment. Hum Brain Mapp 38:1833-1845, 2017. © 2017 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Preliminary studies with (/sup 18/F)haloperidol: a radioligand for in vivo studies of the dopamine receptors

Energy Technology Data Exchange (ETDEWEB)

Tewson, T J; Raichle, M E; Welch, M J [Washington Univ., St. Louis, MO (USA). Edward Mallinckrodt Inst. of Radiology

1980-06-16

The authors report a synthesis of (/sup 18/F)haloperidol of sufficiently high specific activity to permit the mapping of dopamine receptors in vivo in man using PET. The preliminary work with this radioligand in vivo in monkeys clearly suggests that haloperidol enters brain from blood by means of carrier-mediated, facilitated diffusion rather than simple diffusion. This rather surprising observation not only assumes special importance in the interpretation of in vivo pharmacokinetic data on dopamine receptors in man or animals but may also be important in considerations of the possible mode of action of this drug on the central nervous system.

Haloperidol Treatment of Trichotillomania in a Boy with Autism and Mental Retardation.

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Ghaziuddin, M.; And Others

1991-01-01

The report describes the successful treatment of trichotillomania (compulsive hair pulling) in a mentally retarded 11-year-old boy with autism and severe mental retardation. Administration of haloperidol resulted in complete cessation of hair pulling which reappeared when the dosage was decreased and ceased again when dosage was reestablished. (DB)

The PDE10A inhibitor MP-10 and haloperidol produce distinct gene expression profiles in the striatum and influence cataleptic behavior in rodents.

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Gentzel, Renee C; Toolan, Dawn; Roberts, Rhonda; Koser, Amy Jo; Kandebo, Monika; Hershey, James; Renger, John J; Uslaner, Jason; Smith, Sean M

2015-12-01

Phosphodiesterase 10A (PDE10A) has garnered attention as a potential therapeutic target for schizophrenia due to its prominent striatal expression and ability to modulate striatal signaling. The present study used the selective PDE10A inhibitor MP-10 and the dopamine D2 antagonist haloperidol to compare effects of PDE10A inhibition and dopamine D2 blockade on striatopallidal (D2) and striatonigral (D1) pathway activation. Our studies confirmed that administration of MP-10 significantly elevates expression of the immediate early genes (IEG) c-fos, egr-1, and arc in rat striatum. Furthermore, we demonstrated that MP-10 induced egr-1 expression was distributed evenly between enkephalin-containing D2-neurons and substance P-containing D1-neurons. In contrast, haloperidol (3 mg/kg) selectively activated egr-1 expression in enkephalin neurons. Co-administration of MP-10 and haloperidol (0.5 mg/kg) increased IEG expression to a greater extent than either compound alone. Similarly, in a rat catalepsy assay, administration of haloperidol (0.5 mg/kg) or MP-10 (3-30 mg/kg) did not produce cataleptic behavior when dosed alone, but co-administration of haloperidol with MP-10 (3 and 10 mg/kg) induced cataleptic behaviors. Interestingly, co-administration of haloperidol with a high dose of MP-10 (30 mg/kg) failed to produce cataleptic behavior. These findings are important for understanding the neural circuits involved in catalepsy and suggest that the behavioral effects produced by PDE10A inhibitors may be influenced by concomitant medication and the level of PDE10A inhibition achieved by the dose of the inhibitor. Copyright © 2015. Published by Elsevier Ltd.

Intramuscular olanzapine versus intramuscular haloperidol plus lorazepam for the treatment of acute schizophrenia with agitation: An open-label, randomized controlled trial.

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Huang, Charles Lung-Cheng; Hwang, Tzung-Jeng; Chen, Yi-Hsing; Huang, Guan-Hua; Hsieh, Ming H; Chen, Hsiu-Hsi; Hwu, Hai-Gwo

2015-05-01

To compare the efficacy and safety profile between intramuscular (IM) olanzapine and IM haloperidol plus IM lorazepam in acute schizophrenic patients with moderate to severe agitation. This was a prospective, randomized, open-label study. Acutely agitated patients with schizophrenia or schizoaffective disorder (n = 67) were randomized to receive 10 mg IM olanzapine (n = 37) or 5 mg IM haloperidol plus 2 mg IM lorazepam (n = 30). Agitation was measured with Positive and Negative Syndrome Scale Excited Component (PANSS-EC) and Agitation-Calmness Evaluation Scale (ACES) during the first 2 hours and at 24 hours after the first injection. Safety was assessed using the Simpson-Angus Scale and Barnes Akathisia Rating Scale and by recording adverse events at 24 hours following the first injection. The Clinical Global Impression-Severity scale was also rated. The PANSS-EC scores decreased significantly at 2 hours after the first injection in both groups (olanzapine: -10.2, p haloperidol + lorazepam: -9.9, p Haloperidol plus lorazepam was not inferior to olanzapine in reducing agitation at 2 hours. There were no significant differences in PANSS-EC or ACES scores between the two groups within 2 hours following the first injection. The frequencies of adverse events and changes in Clinical Global Impression-Severity, Simpson-Angus Scale, and Barnes Akathisia Rating Scale scores from baseline to 24 hours showed no significant differences between the groups. The findings suggest that IM haloperidol (5 mg) plus lorazepam (2 mg) is not inferior to IM olanzapine (10 mg) in the treatment of acute schizophrenic patients with moderate to severe agitation (ClinialTrials.gov identifier number NCT00797277). Copyright © 2015. Published by Elsevier B.V.

Pharmacodynamic genetic polymorphisms affect adverse drug reactions of haloperidol in patients with alcohol-use disorder

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Zastrozhin MS

2017-07-01

Full Text Available Mikhail Sergeevich Zastrozhin,1,2 Vadim Markovich Brodyansky,3 Valentin Yurievich Skryabin,4 Elena Anatolievna Grishina,5 Dmitry Vladimirovich Ivashchenko,5 Kristina Anatolievna Ryzhikova,5 Ludmila Mikhaylovna Savchenko,1 Alexander Olegovich Kibitov,3 Evgeny Alekseevich Bryun,1,4 Dmitry Alekseevich Sychev6 1Department of Addictology, Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow, Russia; 2Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare, Center for the Prevention of Dependent Behavior, Moscow, Russia; 3Federal Medical Research Centre of Psychiatry and Addictology, Laboratory of Molecular Genetics, Moscow, Russia; 4Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare, Department of Addictology, Moscow, Russia; 5Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Research Centre, Moscow, Russia; 6Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Department of Clinical Pharmacology and Therapy, Moscow, Russia Background: Antipsychotic action of haloperidol is due to blockade of D2 receptors in the mesolimbic dopamine pathway, while the adverse drug reactions are associated with striatal D2 receptor blockade. Contradictory data concerning the effects of genetic polymorphisms of genes encoding these receptors and associated structures (catechol-O-methyltransferase [COMT], glycine transporter and gene encoding the density of D2 receptors on the neuronal membrane are described.Objective: The objectives of this study were to evaluate the correlation between DRD2, SLC6A3 (DAT and COMT genetic polymorphisms and to investigate their effect on the development of adverse drug reactions in patients with alcohol-use disorder who received haloperidol.Patients and methods: The study

Comparison in animal models of 18F-spiroperidol and 18F-haloperidol: potential agents for imaging the dopamine receptor

International Nuclear Information System (INIS)

Welch, M.J.; Kilbourn, M.R.; Mathias, C.J.; Mintun, M.A.; Raichle, M.E.

1983-01-01

Fluorine-18-labeled haloperidol and spiroperidol have been prepared by an exchange reaction using the corresponding non-labeled compound or the nitro analog. Studies in rats have shown that the distribution of labeled spiroperidol has a high striatum to cerebellum ratio which is not observed with haloperidol. A ratio of 10.66 +/- 1.6 is obtained two hours after administration of the 18 F-spiroperidol. When 18 F-spiroperidol was administered to a baboon and tomographic images obtained, the dopamine receptor rich areas were clearly visualized two hours after administration

Haloperidol induces pharmacoepigenetic response by modulating miRNA expression, global DNA methylation and expression profiles of methylation maintenance genes and genes involved in neurotransmission in neuronal cells.

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Swathy, Babu; Banerjee, Moinak

2017-01-01

Haloperidol has been extensively used in various psychiatric conditions. It has also been reported to induce severe side effects. We aimed to evaluate whether haloperidol can influence host methylome, and if so what are the possible mechanisms for it in neuronal cells. Impact on host methylome and miRNAs can have wide spread alterations in gene expression, which might possibly help in understanding how haloperidol may impact treatment response or induce side effects. SK-N-SH, a neuroblasoma cell line was treated with haloperidol at 10μm concentration for 24 hours and global DNA methylation was evaluated. Methylation at global level is maintained by methylation maintenance machinery and certain miRNAs. Therefore, the expression of methylation maintenance genes and their putative miRNA expression profiles were assessed. These global methylation alterations could result in gene expression changes. Therefore genes expressions for neurotransmitter receptors, regulators, ion channels and transporters were determined. Subsequently, we were also keen to identify a strong candidate miRNA based on biological and in-silico approach which can reflect on the pharmacoepigenetic trait of haloperidol and can also target the altered neuroscience panel of genes used in the study. Haloperidol induced increase in global DNA methylation which was found to be associated with corresponding increase in expression of various epigenetic modifiers that include DNMT1, DNMT3A, DNMT3B and MBD2. The expression of miR-29b that is known to putatively regulate the global methylation by modulating the expression of epigenetic modifiers was observed to be down regulated by haloperidol. In addition to miR-29b, miR-22 was also found to be downregulated by haloperidol treatment. Both these miRNA are known to putatively target several genes associated with various epigenetic modifiers, pharmacogenes and neurotransmission. Interestingly some of these putative target genes involved in neurotransmission

Haloperidol induces pharmacoepigenetic response by modulating miRNA expression, global DNA methylation and expression profiles of methylation maintenance genes and genes involved in neurotransmission in neuronal cells.

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Babu Swathy

Full Text Available Haloperidol has been extensively used in various psychiatric conditions. It has also been reported to induce severe side effects. We aimed to evaluate whether haloperidol can influence host methylome, and if so what are the possible mechanisms for it in neuronal cells. Impact on host methylome and miRNAs can have wide spread alterations in gene expression, which might possibly help in understanding how haloperidol may impact treatment response or induce side effects.SK-N-SH, a neuroblasoma cell line was treated with haloperidol at 10μm concentration for 24 hours and global DNA methylation was evaluated. Methylation at global level is maintained by methylation maintenance machinery and certain miRNAs. Therefore, the expression of methylation maintenance genes and their putative miRNA expression profiles were assessed. These global methylation alterations could result in gene expression changes. Therefore genes expressions for neurotransmitter receptors, regulators, ion channels and transporters were determined. Subsequently, we were also keen to identify a strong candidate miRNA based on biological and in-silico approach which can reflect on the pharmacoepigenetic trait of haloperidol and can also target the altered neuroscience panel of genes used in the study.Haloperidol induced increase in global DNA methylation which was found to be associated with corresponding increase in expression of various epigenetic modifiers that include DNMT1, DNMT3A, DNMT3B and MBD2. The expression of miR-29b that is known to putatively regulate the global methylation by modulating the expression of epigenetic modifiers was observed to be down regulated by haloperidol. In addition to miR-29b, miR-22 was also found to be downregulated by haloperidol treatment. Both these miRNA are known to putatively target several genes associated with various epigenetic modifiers, pharmacogenes and neurotransmission. Interestingly some of these putative target genes involved in

Sigma1 and dopamine D2 receptor occupancy in the mouse brain after a single administration of haloperidol and two dopamine D2-like receptor ligands

International Nuclear Information System (INIS)

Ishiwata, Kiichi; Kawamura, Kazunori; Kobayashi, Tadayuki; Matsuno, Kiyoshi

2003-01-01

We investigated sigma 1 and dopamine D 2 receptor occupancy in mouse brain after a single injection of haloperidol, nemonapride, or spiperone using [ 11 C]SA4503 and [ 11 C]raclopride, respectively. Co-injection of the three compounds significantly blocked the uptake of each radioligand. Six hours later, only haloperidol blocked [ 11 C]SA4503 uptake, while all three reduced [ 11 C]raclopride uptake. Sigma 1 receptor occupancy by haloperidol was reduced to 19% at day 2 when D 2 receptor occupancy disappeared. [ 11 C]SA4503 would be applicable to the investigation of sigma 1 receptor occupancy of antispychotic drugs using PET

Treatment response to olanzapine and haloperidol and its association with dopamine D receptor occupancy in first-episode psychosis.

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Zipursky, Robert B; Christensen, Bruce K; Daskalakis, Zafiris; Epstein, Irvin; Roy, Paul; Furimsky, Ivana; Sanger, Todd; Kapur, Shitij

2005-07-01

Response to typical antipsychotic medication has been associated with achieving a level of striatal dopamine D2 receptor occupancy in the range of 65% to 70%. We undertook this study to determine whether response to the atypical antipsychotic olanzapine occurs at lower levels of D2 receptor occupancy. Eighteen patients who presented with a first episode of psychosis were randomized to receive olanzapine 5 mg daily or haloperidol 2 mg daily in a double-blind design. We acquired positron emission tomography (PET) scans using the D2 ligand [11C]raclopride within the first 15 days of treatment to determine the percentage of D2 receptors occupied by the medication. According to response, dosage was then adjusted to a maximum dosage of 20 mg daily of either drug. PET scans were repeated after 10 to 12 weeks of treatment. At the first PET scan, the 8 olanzapine-treated patients had significantly lower D2 receptor occupancies (mean 63.4%, SD 7.3) than those observed in the 10 patients treated with haloperidol (mean 73.0%, SD 6.1). When patients were rescanned following dosage adjustment, mean D2 receptor occupancies were greater than 70% in both groups. D2 receptor occupancies did not differ significantly between the olanzapine-treated group (mean 72.0%, SD 5.7) and the haloperidol-treated group (mean 78.7%, SD 7.6). These results suggest that, in patients being treated for a first episode of psychosis, olanzapine has its antipsychotic effect at approximately the same levels of D2 receptor occupancy as are achieved with low dosages of haloperidol.

Dosimetry of photosensitization by ultraviolet in patients treated with Haloperidol and Piportil

International Nuclear Information System (INIS)

Barros, M. de; Araujo, C.C.

1982-01-01

It has been postulated that visible light on UV may induce photosensitization in chronic psycotics, under phenotiazine or butyrofenone therapy. The possible sensitization with UV, in patients with Haloperidol (Johnson and Johnson) or Piportil (Rhodia) treatments is described. Under experimental conditions, a surpassable photosensitizations in reaction groups aren't finding, when paired with the control ones. (M.A.C.) [pt

Positron emission tomography with (18F)methylspiperone demonstrates D2 dopamine receptor binding differences of clozapine and haloperidol

International Nuclear Information System (INIS)

Karbe, H.; Wienhard, K.; Huber, M.; Herholz, K.; Heiss, W.D.; Hamacher, K.; Coenen, H.H.; Stoecklin, G.; Loevenich, A.

1991-01-01

Four schizophrenic patients were investigated with dynamic positron emission tomography (PET) using ( 18 F)fluorodeoxyglucose (FDG) and ( 18 F)methylspiperone (MSP) as tracers. Two schizophrenics were on haloperidol therapy at the time of MSP PET. The other two schizophrenics were treated with clozapine, in one of them MSP PET was carried out twice with different daily doses (100 mg and 450mg respectively). Neuroleptic serum levels were measured in all patients. Results were compared with MSP PET of two drugfree male control subjects and with a previous fluoroethylspiperone (FESP) study of normals. Three hours after tracer injection specific binding of MSP was observed in the striatum in all cases. The striatum to cerebellum ratio was used to estimate the degree of neuroleptic-caused striatal D 2 dopamine receptor occupancy. In the haloperidol treated patients MSP binding was significantly decreased, whereas in the clozapine treated patients striatum to cerebellum ratio was normal. Even the increase of clozapine dose in the same patient had no influence on this ratio. Despite the smaller number of patients the study shows for the first time in humans that striatal MSP binding reflects the different D 2 dopamine receptor affinities of clozapine and haloperidol. (authors)

Frequency of sexual dysfunction and other reproductive side-effects in patients with schizophrenia treated with risperidone, olanzapine, quetiapine, or haloperidol: the results of the EIRE study.

Science.gov (United States)

Bobes, J; Garc A-Portilla, M P; Rejas, J; Hern Ndez, G; Garcia-Garcia, M; Rico-Villademoros, F; Porras, A

2003-01-01

Atypical antipsychotics seem to differ mainly in their tolerability profile. The aim of this cross-sectional study, the Estudio de Investigaci n de Resultados en Esquizofrenia (Outcomes Research Study in Schizophrenia; EIRE study), was to assess in a clinical setting the frequency of several side-effects related to haloperidol, risperidone, olanzapine, and quetiapine. This article addresses sexual dysfunction and other reproductive side-effects (gynecomastia, menorrhage, amenorrhea, and galactorrhea). We recruited outpatients diagnosed with schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders (DSM-IV; American Psychiatric Association, 1994) criteria and who had received a single antipsychotic (risperidone, olanzapine, quetiapine, or haloperidol) for at least 4 weeks. During a single visit, we collected data, including demographic and clinical characteristics, current antipsychotic and concomitant treatment, and adverse effects listed in a modified version of the UKU Scale. We used a Chi-squared test to determine pairs comparisons of the frequency of adverse reactions between treatments. To estimate risk of a given adverse reaction with a given treatment, we used a logistic regression method. We assessed 636 evaluable patients out of 669 recruited. Frequency of sexual dysfunction was high with haloperidol (38.1%) and also with olanzapine (35.3%), quetiapine (18.2%), and risperidone (43.2%). We found the frequency of other reproductive side-effects to be relatively low with all four drugs: haloperidol (6.9%), olanzapine (6.4%), quetiapine (2.7%), and risperidone (11.7%). Sexual dysfunction appeared to be dose-related with haloperidol, risperidone, and olanzapine. Risperidone and olanzapine showed a higher risk of sexual dysfunction and other reproductive sideeffects than haloperidol. Quetiapine showed a lower risk of sexual dysfunction during short-term treatment ( 12 weeks) are lacking. Our results suggest that none of the atypical

Pharmacodynamics and pharmacokinetics of haloperidol and reduced haloperidol in schizophrenic patients.

Science.gov (United States)

Chang, W H; Lin, S K; Jann, M W; Lam, Y W; Chen, T Y; Chen, C T; Hu, W H; Yeh, E K

1989-07-01

Twelve male chronic schizophrenic inpatients, neuroleptic-free for at least 4 weeks, were given an oral test dose of 10 mg haloperidol (HAL) and reduced HAL (RHAL) in a random order, with a 2-week interval. Two weeks after the last test dose, the patients were given HAL, 5 mg orally twice daily for 7 days. Blood samples were drawn at baseline and between 0.5 and 24 hr after the test doses, and during HAL treatment as well. Plasma drug concentrations and homovanillic acid (HVA) levels were measured with high-performance liquid chromatography using electrochemical detection. HAL, but not RHAL, produced increments in plasma HVA (pHVA) levels at 24 hr after a test dose. pHVA levels remained higher than baseline during HAL treatment. Detectable interconversion between HAL and RHAL was observed in eight patients. The capacity of the reductive drug-metabolizing enzyme system, however, was greater than that of the oxidative processes. The plasma RHAL:HAL ratios on days 6 and 7 were higher than and positively correlated with those at Tmax after a single dose of HAL and were negatively correlated with the HAL:RHAL ratios at Tmax after a single dose of RHAL. Thus, both reductive and oxidative drug-metabolizing systems probably contribute to individual differences in plasma RHAL:HAL ratios in HAL-treated schizophrenic patients.

Differential Effects of Olanzapine and Haloperidol on MK-801-induced Memory Impairment in Mice

Science.gov (United States)

Song, Jae Chun; Seo, Mi Kyoung; Park, Sung Woo; Lee, Jung Goo; Kim, Young Hoon

2016-01-01

Objective We investigated the differential effects of the antipsychotic drugs olanzapine and haloperidol on MK-801-induced memory impairment and neurogenesis in mice. Methods MK-801 (0.1 mg/kg) was administered 20 minutes prior to behavioral testing over 9 days. Beginning on the sixth day of MK-801 treatment, either olanzapine (0.05 mg/kg) or haloperidol (0.05 mg/kg) was administered 40 minutes prior to MK-801 for the final 4 days. Spatial memory performance was measured using a Morris water maze (MWM) test for 9 days (four trials/day). Immunohistochemistry with bromodeoxyuridine (BrdU) was used to identify newborn cells labeled in tissue sections from the dentate gyrus of the hippocampus. Results MK-801 administration over 9 days significantly impaired memory performance in the MWM test compared to untreated controls (p801 also resulted in a decrease in the number of BrdU-labeled cells in the dentate gyrus (28.6%; p801 in mice via the stimulating effects of neurogenesis. PMID:27489382

Cardiac conductive disturbance in patients with polycystic ovary syndrome.

Science.gov (United States)

Huang, Jen-Hung; Tsai, Jen-Chen; Hsu, Ming-I; Chen, Yi-Jen

2010-12-01

Polycystic ovary syndrome (PCOS) is the most common endocrine abnormality of reproductive-aged women and increases the risk of cardiovascular disease. However, the effects of PCOS on electrocardiograms (ECGs) are not fully elucidated. The aim of this study was to evaluate the characteristics of ECGs in patients with PCOS. This study included 24 patients with PCOS and 12 patients without PCOS. The heart rate, PR interval, QRS duration, Sokolow-Lyon voltage (SV1 + RV5/6), Cornell voltage (RaVL + SV3), QT interval and QTc interval were measured in 12-lead ECGs. The QRS duration was wider in patients with PCOS than those without PCOS (91 ± 8 vs. 81 ± 10 ms, p heart rate, PR interval, Sokolow-Lyon voltage, product of the QRS duration times Cornell voltage combination, QT interval, QTc interval, QT dispersion and QTc dispersion were similar between the two groups. PCOS is associated with a widening QRS duration, which may contribute to its increased cardiovascular risks.

Effects of the hydroethanolic extract of Mucuna pruriens (L.) DC (Fabaceae) on haematological profile in normal and haloperidol treated rats.

Science.gov (United States)

Akindele, Abidemi J; Busayo, Fadeyibi I

2011-01-01

Mucuna pruriens (L.) DC (Fabaceae) is a climbing plant claimed in traditional medicine to possess anti-anaemic effect. The study is to investigate the effects of the hydroethanolic extract of M. pruriens (MP) on haematological profile in normal and haloperidol treated rats. MP was administered p.o. at doses of 50, 100, 200, and 400 mg/kg to groups of rats daily for 28 days. Control animals received distilled water. Rats were sacrificed on the 28th day and blood samples collected for evaluation of haematological parameters and serum iron. Another set of animals received MP p.o. at same doses but along with haloperidol (0.2 mg/kg, i.p.) daily for 4 days. Three other groups of rats received distilled water, haloperidol, and MP at 400 mg/kg alone. Haematological parameters and serum iron were determined. Extract iron content, phytochemical analysis and acute toxicity studies were also carried out. MP administered to normal rats for 28 days significantly (p Mucuna pruriens possibly possess beneficial effects in anaemic conditions especially associated with iron deficiency.

Modulation of haloperidol-induced patterns of the transcription factor Nur77 and Nor-1 expression by serotonergic and adrenergic drugs in the mouse brain

Science.gov (United States)

Maheux, Jérôme; Vuillier, Laura; Mahfouz, Mylène; Rouillard, Claude; Lévesque, Daniel

2015-01-01

Different patterns of expression of the transcription factors of Nur77 and Nor-1 are induced following acute administration of typical and atypical antipsychotic drugs. The pharmacological profile of atypical antipsychotics suggests that serotonergic and/or adrenergic receptors might contribute to these reported differences. In order to test this possibility, we examined the abilities of serotonin 5-HT1A and 5-HT2A/2C, and α1- and α2-adrenergic receptor drugs to modify the pattern of Nur77 (NR4A1) and Nor-1 (NR4A3) mRNA expression induced by haloperidol. Various groups of mice were treated with either saline, DOI, a 5-HT2A/2C agonist, MDL11939, a 5-HT2A antagonist, 8-OH-DPAT, a 5-HT1A agonist, prazosin, an α1-adrenergic antagonist and idazoxan, an α2-adrenergic antagonist, alone or in combination with haloperidol. The 5-HT2A/2C agonist DOI alone significantly increased Nur77 expression in the medial striatum and nucleus accumbens. DOI reduced Nor-1 expression, while MDL11939 increased the expression of this transcript in the cortex. Prazosin reduced Nur77 expression in the dorsal striatum and nucleus accumbens. Interestingly, 8-OH-DPAT and MDL11939 partially prevented haloperidol-induced Nur77 up-regulation, while MDL11939 completely abolished Nor-1 expression in the striatum. In addition, MDL11939 decreased haloperidol-induced Nur77 and Nor-1 mRNA levels in the ventral tegmental area. On the contrary, idazoxan (α2 antagonist) consistently potentiated haloperidol-induced Nur77, but not Nor-1 mRNA levels in the striatum, whereas prazosin (α1 antagonist) remained without effect. Taken together, these results show the ability of a 5-HT1A agonist or a 5-HT2A antagonist to reduce haloperidol-induced Nur77 and Nor-1 striatal expression, suggesting that these serotonin receptor subtypes participate in the differential pattern of gene expression induced by typical and atypical antipsychotic drugs. PMID:21524335

Protective effect of Curcumin, the active principle of turmeric (Curcuma longa) in haloperidol-induced orofacial dyskinesia and associated behavioural, biochemical and neurochemical changes in rat brain.

Science.gov (United States)

Bishnoi, Mahendra; Chopra, Kanwaljit; Kulkarni, Shrinivas K

2008-02-01

Tardive dyskinesia (TD) is a motor disorder of the orofacial region resulting from chronic neuroleptic treatment. A high incidence and irreversibility of this hyperkinetic disorder has been considered a major clinical issue in the treatment of schizophrenia. The molecular mechanism related to the pathophysiology of tardive dyskinesia is not completely known. Various animal studies have demonstrated an enhanced oxidative stress and increased glutamatergic transmission as well as inhibition in the glutamate uptake after the chronic administration of haloperidol. The present study investigated the effect of curcumin, an antioxidant, in haloperidol-induced tardive dyskinesia by using different behavioural (orofacial dyskinetic movements, stereotypy, locomotor activity, % retention), biochemical (lipid peroxidation, reduced glutathione levels, antioxidant enzyme levels (SOD and catalase) and neurochemical (neurotransmitter levels) parameters. Chronic administration of haloperidol (1 mg/kg i.p. for 21 days) significantly increased vacuous chewing movements (VCM's), tongue protrusions, facial jerking in rats which was dose-dependently inhibited by curcumin. Chronic administration of haloperidol also resulted in increased dopamine receptor sensitivity as evident by increased locomotor activity and stereotypy and also decreased % retention time on elevated plus maze paradigm. Pretreatment with curcumin reversed these behavioral changes. Besides, haloperidol also induced oxidative damage in all major regions of brain which was attenuated by curcumin, especially in the subcortical region containing striatum. On chronic administration of haloperidol, there was a decrease in turnover of dopamine, serotonin and norepinephrine in both cortical and subcortical regions which was again dose-dependently reversed by treatment with curcumin. The findings of the present study suggested for the involvement of free radicals in the development of neuroleptic-induced tardive dyskinesia and

Effects of haloperidol and cocaine pretreatments on brain distribution and kinetics of [11C]methamphetamine in methamphetamine sensitized dog: Application of PET to drug pharmacokinetic study

International Nuclear Information System (INIS)

Nakamura, Hitoshi; Hishinuma, Takanori; Tomioka, Yoshihisa; Ishiwata, Shunji; Ido, Tatsuo; Iwata, Ren; Funaki, Yoshihito; Itoh, Masatoshi; Fujiwara, Takehiko; Yanai, Kazuhiko; Sato, Mitsumoto; Numachi, Yohtaro; Yoshida, Sumiko; Mizugaki, Michinao

1997-01-01

Repeated administration of methamphetamine (MAP) causes behavioral sensitization in animals. We previously reported that the maximum accumulation level of [ 11 C]MAP in the MAP-sensitized dog brain was 1.4 times higher than that in the control. In behavioral studies, haloperidol (a dopamine D 2 receptor antagonist) prevents MAP-induced behavioral sensitization, and cocaine (a dopamine reuptake blocker) has the cross-behavioral sensitization with MAP. In the present study, to elucidate the relation between the MAP-induced behavioral sensitization and the pharmacokinetics of MAP, we investigated the effects of haloperidol and cocaine pretreatments on brain regional distribution and kinetics of [ 11 C]MAP using positron emission tomography (PET). A significant increase of [ 11 C]MAP uptake into the sensitized dog brain was prevented by haloperidol and cocaine pretreatments. These pharmacokinetic changes were not due to the changes in the rate of MAP metabolism. These results suggest haloperidol and cocaine can change the cerebral pharmacokinetic profile of MAP in the behavioral-sensitized dog. The variations of MAP-accumulation may affect the development or expression of MAP-induced behavioral sensitization

Adverse drug reactions of haloperidol used in critically ill children for the treatment of delirium

NARCIS (Netherlands)

Spaans, E.; Slooff, V.; Van Puijenbroek, E.; Jessurun, N.; De Hoog, M.; Tibboel, D.; De Wildt, S.

BACKGROUND: As delirium in critically ill children is increasingly recognized, more children are treated with the antipsychotic drug haloperidol. However, little is known about its safety in this context. The objective of this study was to investigate the incidence and nature of adverse events

Effects of cannabinoid CB(1) receptor agonism and antagonism on SKF81297-induced dyskinesia and haloperidol-induced dystonia in Cebus apella monkeys

DEFF Research Database (Denmark)

Madsen, Morten V; Peacock, Linda P; Werge, Thomas

2011-01-01

81297 (SKF) and acute dystonia induced by the dopamine D(2) receptor antagonist haloperidol in Cebus apella monkeys. The monkeys were sensitised to EPS by prior exposure to D(2) receptor antagonists. SKF (0.3 mg/kg) was administered alone and in combination with the CB(1) agonist CP55,940 (0.......0025-0.01 mg/kg) or the CB(1) antagonist SR141716A (0.25-0.75 mg/kg). Haloperidol (individual doses at 0.01-0.02 mg/kg) was administered alone and in combination with CP55,940 (0.005 or 0.01 mg/kg) or SR141716A (0.5 or 0.75 mg/kg). Subsequently, the monkeys were videotaped, and the recordings were rated...... for oral dyskinesia or dystonia. SKF-induced oral dyskinesia was dose-dependently reduced by CP55,940, with no effect of SR141716A. Haloperidol-induced dystonia was not affected by either CP55,940 or SR141716A....

Stevens-Johnson syndrome progressing to toxic epidermal necrolysis with haloperidol and carbamazepine combination

Directory of Open Access Journals (Sweden)

Ajay Kumar

2011-01-01

Full Text Available Carbamazepine and other anticonvulsants are commoner cause of severe adverse cutaneous drug reactions such as erythema multiforme, toxic epidermal necrolysis (TEN, and Stevens-Johnson syndrome (SJS. We report a case of SJS rapidly progressing to TEN with a combination of haloperidol and carbamazepine in a patient with bipolar affective disorder. The pathophysiological mechanism underlying this reaction is discussed.

Schizophrenia and viral infection in animal model: chronic administration of haloperidol and clozapine

Czech Academy of Sciences Publication Activity Database

Tejkalová, H.; Ruml, T.; Rumlová, M.; Klaschka, Jan; Šťastný, František

2007-01-01

Roč. 18, Suppl. 1 (2007), s68-s69 ISSN 0955-8810. [Biennial Meeting of the European Behavioural Pharmacology Society /12./. 31.08.2007-03.09.2007, Tübingen] R&D Projects: GA MZd NF7626 Institutional research plan: CEZ:AV0Z10300504; CEZ:AV0Z50110509 Keywords : schizophrenia * rat * clozapine * haloperidole * behaviour Subject RIV: BB - Applied Statistics, Operational Research

Effects of aripiprazole and haloperidol on neural activation during the n-back in healthy individuals: A functional MRI study.

Science.gov (United States)

Goozee, Rhianna; Reinders, Antje A T S; Handley, Rowena; Marques, Tiago; Taylor, Heather; O'Daly, Owen; McQueen, Grant; Hubbard, Kathryn; Mondelli, Valeria; Pariante, Carmine; Dazzan, Paola

2016-06-01

Antipsychotic drugs target neurotransmitter systems that play key roles in working memory. Therefore, they may be expected to modulate this cognitive function via their actions at receptors for these neurotransmitters. However, the precise effects of antipsychotic drugs on working memory function remain unclear. Most studies have been carried out in clinical populations, making it difficult to disentangle pharmacological effects from pathology-related brain activation. In this study, we aim to investigate the effects of two antipsychotic compounds on brain activation during working memory in healthy individuals. This would allow elucidation of the effects of current antipsychotic treatments on brain function, independently of either previous antipsychotic use or disease-related pathology. We carried out a fully counterbalanced, randomised within-subject, double-blinded and placebo-controlled, cross-over study of the effects of two antipsychotic drugs on working memory function in 17 healthy individuals, using the n-back task. Participants completed the functional MRI task on three separate occasions (in randomised order): following placebo, haloperidol, and aripiprazole. For each condition, working memory ability was investigated, and maps of neural activation were entered into a random effects general linear regression model to investigate main working memory function and linear load. Voxel-wise and region of interest analyses were conducted to attain regions of altered brain activation for each intervention. Aripiprazole did not lead to any changes in neural activation compared with placebo. However, reaction time to a correct response was significantly increased following aripiprazole compared to both placebo (p=0.046) and haloperidol (p=0.02). In contrast, compared to placebo, haloperidol dampened activation in parietal (BA 7/40; left: FWE-corr. p=0.005; FWE-corr. right: p=0.007) and frontal (including prefrontal; BA 9/44/46; left: FWE-corr. p=0.009; right: FWE

The effect of colloid preload versus prophylactic ephedrine ...

African Journals Online (AJOL)

Aim: We aimed to investigate the effect of colloid infusion immediately before the spinal anesthesia, and the prophylactic intravenous (IV) infusion of ephedrine after injection of intrathecal bupivacaine on hemodynamic parameters, QT, The QT interval corrected for heart rate (QTc), and dispersion of QTc (QTcDisp) intervals ...

Effects of haloperidol and cocaine pretreatments on brain distribution and kinetics of [{sup 11}C]methamphetamine in methamphetamine sensitized dog: Application of PET to drug pharmacokinetic study

Energy Technology Data Exchange (ETDEWEB)

Nakamura, Hitoshi; Hishinuma, Takanori; Tomioka, Yoshihisa; Ishiwata, Shunji; Ido, Tatsuo; Iwata, Ren; Funaki, Yoshihito; Itoh, Masatoshi; Fujiwara, Takehiko; Yanai, Kazuhiko; Sato, Mitsumoto; Numachi, Yohtaro; Yoshida, Sumiko; Mizugaki, Michinao

1997-02-01

Repeated administration of methamphetamine (MAP) causes behavioral sensitization in animals. We previously reported that the maximum accumulation level of [{sup 11}C]MAP in the MAP-sensitized dog brain was 1.4 times higher than that in the control. In behavioral studies, haloperidol (a dopamine D{sub 2} receptor antagonist) prevents MAP-induced behavioral sensitization, and cocaine (a dopamine reuptake blocker) has the cross-behavioral sensitization with MAP. In the present study, to elucidate the relation between the MAP-induced behavioral sensitization and the pharmacokinetics of MAP, we investigated the effects of haloperidol and cocaine pretreatments on brain regional distribution and kinetics of [{sup 11}C]MAP using positron emission tomography (PET). A significant increase of [{sup 11}C]MAP uptake into the sensitized dog brain was prevented by haloperidol and cocaine pretreatments. These pharmacokinetic changes were not due to the changes in the rate of MAP metabolism. These results suggest haloperidol and cocaine can change the cerebral pharmacokinetic profile of MAP in the behavioral-sensitized dog. The variations of MAP-accumulation may affect the development or expression of MAP-induced behavioral sensitization.

Haloperidol-loaded lipid-core polymeric nanocapsules reduce DNA damage in blood and oxidative stress in liver and kidneys of rats

International Nuclear Information System (INIS)

Roversi, Katiane; Benvegnú, Dalila M.; Roversi, Karine; Trevizol, Fabíola; Vey, Luciana T.; Elias, Fabiana; Fracasso, Rafael

2015-01-01

Haloperidol (HP) nanoencapsulation improves therapeutic efficacy, prolongs the drug action time, and reduces its motor side effects. However, in a view of HP toxicity in organs like liver and kidneys in addition to the lack of knowledge regarding the toxicity of polymeric nanocapsules, our aim was to verify the influence of HP-nanoformulation on toxicity and oxidative stress markers in the liver and kidneys of rats, also observing the damage caused in the blood. For such, 28 adult male Wistar rats were designated in four experimental groups (n = 7) and treated with vehicle (C group), free haloperidol suspension (FH group), blank nanocapsules suspension (B-Nc group), and haloperidol-loaded lipid-core nanocapsules suspension (H-Nc group). The nanocapsules formulation presented the size of approximately 250 nm. All suspensions were administered to the animals (0.5 mg/kg/day-i.p.) for a period of 28 days. Our results showed that FH caused damage in the liver, evidenced by increased lipid peroxidation, plasma levels of aspartate aminotransferase, and alanine aminotransferase, as well as decreased cellular integrity and vitamin C levels. In kidneys, FH treatment caused damage to a lesser extent, observed by decreased activity of δ-aminolevulinate dehydratase (ALA-D) and levels of VIT C. In addition, FH treatment was also related to a higher DNA damage index in blood. On the other hand, animals treated with H-Nc and B-Nc did not show damage in liver, kidneys, and DNA. Our study indicates that the nanoencapsulation of haloperidol was able to prevent the sub-chronic toxicity commonly observed in liver, kidneys, and DNA, thus reflecting a pharmacological superiority in relation to free drug

Haloperidol-loaded lipid-core polymeric nanocapsules reduce DNA damage in blood and oxidative stress in liver and kidneys of rats

Science.gov (United States)

Roversi, Katiane; Benvegnú, Dalila M.; Roversi, Karine; Trevizol, Fabíola; Vey, Luciana T.; Elias, Fabiana; Fracasso, Rafael; Motta, Mariana H.; Ribeiro, Roseane F.; dos S. Hausen, Bruna; Moresco, Rafael N.; Garcia, Solange C.; da Silva, Cristiane B.; Burger, Marilise E.

2015-04-01

Haloperidol (HP) nanoencapsulation improves therapeutic efficacy, prolongs the drug action time, and reduces its motor side effects. However, in a view of HP toxicity in organs like liver and kidneys in addition to the lack of knowledge regarding the toxicity of polymeric nanocapsules, our aim was to verify the influence of HP-nanoformulation on toxicity and oxidative stress markers in the liver and kidneys of rats, also observing the damage caused in the blood. For such, 28 adult male Wistar rats were designated in four experimental groups ( n = 7) and treated with vehicle (C group), free haloperidol suspension (FH group), blank nanocapsules suspension (B-Nc group), and haloperidol-loaded lipid-core nanocapsules suspension (H-Nc group). The nanocapsules formulation presented the size of approximately 250 nm. All suspensions were administered to the animals (0.5 mg/kg/day-i.p.) for a period of 28 days. Our results showed that FH caused damage in the liver, evidenced by increased lipid peroxidation, plasma levels of aspartate aminotransferase, and alanine aminotransferase, as well as decreased cellular integrity and vitamin C levels. In kidneys, FH treatment caused damage to a lesser extent, observed by decreased activity of δ-aminolevulinate dehydratase (ALA-D) and levels of VIT C. In addition, FH treatment was also related to a higher DNA damage index in blood. On the other hand, animals treated with H-Nc and B-Nc did not show damage in liver, kidneys, and DNA. Our study indicates that the nanoencapsulation of haloperidol was able to prevent the sub-chronic toxicity commonly observed in liver, kidneys, and DNA, thus reflecting a pharmacological superiority in relation to free drug.

Haloperidol-loaded lipid-core polymeric nanocapsules reduce DNA damage in blood and oxidative stress in liver and kidneys of rats

Energy Technology Data Exchange (ETDEWEB)

Roversi, Katiane, E-mail: katianeroversi@gmail.com [Universidade Federal de Santa Maria, Programa de Pós-Graduação em Farmacologia (Brazil); Benvegnú, Dalila M., E-mail: dalilabenvegnu@yahoo.com.br [Universidade Federal da Fronteira Sul (UFFS), Bioquímica e Farmacologia (Brazil); Roversi, Karine, E-mail: karineroversi-@hotmail.com [Universidade Federal de Santa Maria (UFSM), Departamento de Fisiologia e Farmacologia, Centro de Ciências da Saúde (Brazil); Trevizol, Fabíola, E-mail: fatrevizol@yahoo.com.br [Universidade Federal de Santa Maria, Programa de Pós-Graduação em Farmacologia (Brazil); Vey, Luciana T., E-mail: luciana.taschetto@hotmail.com [Universidade Federal de Santa Maria (UFSM), Departamento de Fisiologia e Farmacologia, Centro de Ciências da Saúde (Brazil); Elias, Fabiana, E-mail: fabiana.elias@uffs.edu.br [Universidade Federal da Fronteira Sul (UFFS), Bioquímica e Farmacologia (Brazil); Fracasso, Rafael, E-mail: rafael.fra@hotmail.com [Universidade Federal do Rio Grande do Sul, Programa de Pós-Graduação em Ciências Farmacêuticas (Brazil); and others

2015-04-15

Haloperidol (HP) nanoencapsulation improves therapeutic efficacy, prolongs the drug action time, and reduces its motor side effects. However, in a view of HP toxicity in organs like liver and kidneys in addition to the lack of knowledge regarding the toxicity of polymeric nanocapsules, our aim was to verify the influence of HP-nanoformulation on toxicity and oxidative stress markers in the liver and kidneys of rats, also observing the damage caused in the blood. For such, 28 adult male Wistar rats were designated in four experimental groups (n = 7) and treated with vehicle (C group), free haloperidol suspension (FH group), blank nanocapsules suspension (B-Nc group), and haloperidol-loaded lipid-core nanocapsules suspension (H-Nc group). The nanocapsules formulation presented the size of approximately 250 nm. All suspensions were administered to the animals (0.5 mg/kg/day-i.p.) for a period of 28 days. Our results showed that FH caused damage in the liver, evidenced by increased lipid peroxidation, plasma levels of aspartate aminotransferase, and alanine aminotransferase, as well as decreased cellular integrity and vitamin C levels. In kidneys, FH treatment caused damage to a lesser extent, observed by decreased activity of δ-aminolevulinate dehydratase (ALA-D) and levels of VIT C. In addition, FH treatment was also related to a higher DNA damage index in blood. On the other hand, animals treated with H-Nc and B-Nc did not show damage in liver, kidneys, and DNA. Our study indicates that the nanoencapsulation of haloperidol was able to prevent the sub-chronic toxicity commonly observed in liver, kidneys, and DNA, thus reflecting a pharmacological superiority in relation to free drug.

Possible biomarkers modulating haloperidol efficacy and/or tolerability.

Science.gov (United States)

Porcelli, Stefano; Crisafulli, Concetta; Calabrò, Marco; Serretti, Alessandro; Rujescu, Dan

2016-04-01

Haloperidol (HP) is widely used in the treatment of several forms of psychosis. Despite of its efficacy, HP use is a cause of concern for the elevated risk of adverse drug reactions. adverse drug reactions risk and HP efficacy greatly vary across subjects, indicating the involvement of several factors in HP mechanism of action. The use of biomarkers that could monitor or even predict HP treatment impact would be of extreme importance. We reviewed the elements that could potentially be used as peripheral biomarkers of HP effectiveness. Although a validated biomarker still does not exist, we underlined the several potential findings (e.g., about cytokines, HP metabolites and genotypic biomarkers) which could pave the way for future research on HP biomarkers.

QT interval correction for drug-induced changes in body temperature during integrated cardiovascular safety assessment in regulatory toxicology studies in dogs: A case study.

Science.gov (United States)

El Amrani, Abdel-Ilah; El Amrani-Callens, Francine; Loriot, Stéphane; Singh, Pramila; Forster, Roy

2016-01-01

Cardiovascular safety assessment requires accurate evaluation of QT interval, which depends on the length of the cardiac cycle and also on core body temperature (BT). Increases in QT interval duration have been shown to be associated with decreases in BT in dogs. An example of altered QT interval duration associated with changes in body temperature observed during a 4-week regulatory toxicology study in dogs is presented. Four groups of Beagle dogs received the vehicle or test item once on Day 1, followed by a 4-week observation period. Electrocardiogram (ECG) parameters were continuously recorded on Days 1 and 26 by jacketed external telemetry (JET). Core body temperature (BT) was measured with a conventional rectal thermometer at appropriate time-points during the Day 1 recording period. Decreased BT was observed approximately 2h after treatment on Day 1, along with increased QT interval duration corrected according to the Van de Water formula (QTcV), but the effect was no longer observed after correction for changes in BT [QTcVcT=QTcV-14(37.5-BT)] according to the Van der Linde formula. No significant changes in QTcV were reported at the end of the observation period, on Day 26. The present study demonstrates that core body (rectal) temperature can easily be monitored at appropriate time-points during JET recording in regulatory toxicology studies in dogs, in order to correct QT interval duration values for treatment-related changes in BT. The successful application of the Van der Linde formula to correct QTc prolongation for changes in BT was demonstrated. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Dose-Dependent Effects of Methadone on QT interval in Patients under Methadone Maintenance Treatment

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Farzad Gheshlaghi

2013-03-01

Full Text Available Background: The role of methadone in QTc prolongation, Torsades de Pointes (TdP arrhythmia and sudden cardiac death has been debated. Because of widespread use of methadone in methadone maintenance treatment (MMT centers, we aimed to study dose-related effects of methadone on QTc prolongation. Methods: In a comparative observational study, 90 patients who were under MMT were evaluated. Patients were divided into three groups according to methadone daily dose (G1: 0-59 mg, G2: 60-109 mg, G3: 110-150 mg. Twelve-lead electrocardiograms (ECG were performed at baseline and two months later, after reaching the maximum daily dose of methadone. The QTc were calculated for each patient. Comparison of mean QTc and mean QTc prolongation between baseline and follow up ECGs were analyzed. Results: In total, mean (SD age was 32.4 (8.5. TdP was not detected in any patients. Mean QTc was 405.2 (17.0 and 418.5 (23.1 msec before and two months after MMT respectively. There was a significant difference between mean QTc in each group before and after treatment (P

Qt interval prolongation and ventricular arrhythmias in patients with chronic heart failure

International Nuclear Information System (INIS)

Sarwar, M.; Majeed, S.M.I.; Khan, M.A.; Majeed, S.M.

2014-01-01

To determine the association of QTc interval prolongation with ventricular arrhythmias in patients with chronic heart failure. Study Design: Descriptive study. Place and Duration of Study: This study was conducted at Armed Forces Institute of Cardiology/National Institute of Heart Diseases, Rawalpindi, Pakistan from April 2013 to August 2013. Patients and Methods: Fifty three heart failure patients were monitored for 48 hours using ambulatory holter electrocardiography recorders. Digital ECG data was analyzed for QTc interval along with frequency and severity of arrhythmias. Association of prolonged QTc interval with ventricular arrhythmias and severity of arrhythmias was analyzed. Results: Cardiac arrhythmias were observed in 79.2% patients. QT analysis revealed that 69.8% patients had prolonged QTc interval, 86.4% patients with prolonged QTc had ventricular arrhythmias. Of these 66% patients were found to have severe ventricular arrhythmias. Comparison of mean QTc interval of our study population with a reference value showed significantly higher QTc interval of our study group than the test value. Conclusion: Arrhythmia frequency and severity significantly increases with an increase in QTc interval in heart failure demonstrating association of prolonged QTc interval with high risk of severe ventricular arrhythmias and sudden cardiac death in chronic heart failure. (author)

Electrochemical behaviour of some neuroleptics: Haloperidol and its derivatives.

Science.gov (United States)

Vire, J C; Fischer, M; Patriarche, G J; Christian, G D

1981-05-01

The electrochemical characteristics of Haloperidol and related compounds, representative neuroleptics of the butyrophenone family, have been investigated as a function of pH and concentration by direct-current, alternating-current and differential-pulse polarography and cyclic voltammetry at a hanging mercury drop electrode. A single cathodic wave representing an irreversible two-electron reduction is obtained, and its half-wave potential differs from that characteristic of aromatic ketone reduction. Adsorption processes disturb the wave behaviour and an adsorption prewave is observed at high concentrations. Quantitative measurements were successful in the concentration range 1 x 10(-4)-1 x 10(-6)M (0.4 mg/l.), the lower concentration representing the detection limit by differential-pulse polarography.

Impact of haloperidol and quetiapine on the expression of genes encoding antioxidant enzymes in human neuroblastoma SH-SY5Y cells.

Science.gov (United States)

Schmidt, Andreas Johannes; Hemmeter, Ulrich Michael; Krieg, Jürgen-Christian; Vedder, Helmut; Heiser, Philip

2009-05-01

Antipsychotics are known to alter antioxidant activities in vivo. Therefore, the aim of the present study was to examine in the human neuroblastoma SH-SY5Y cell line the impact of a typical (haloperidol) and an atypical (quetiapine) antipsychotic on the expression of genes encoding the key enzymes of the antioxidant metabolism (Cu, Zn superoxide dismutase; Mn superoxide dismutase; glutathione peroxidase; catalase) and enzymes of the glutathione metabolism (gamma-glutamyl cysteine synthetase, glutathione-S-transferase, gamma-glutamyltranspeptidase, glutathione reductase). The cells were incubated for 24h with 0.3, 3, 30 and 300microM haloperidol and quetiapine, respectively; mRNA levels were measured by polymerase chain reaction. In the present study, we observed mostly significant decreases of mRNA contents. With respect to the key pathways, we detected mainly effects on the mRNA levels of the hydrogen peroxide detoxifying enzymes. Among the enzymes of the glutathione metabolism, glutathione-S-transferase- and gamma-glutamyltranspeptidase-mRNA levels showed the most prominent effects. Taken together, our results demonstrate a significantly reduced expression of genes encoding for antioxidant enzymes after treatment with the antipsychotics, haloperidol and quetiapine.

Haloperidol dose combined with dexamethasone for PONV prophylaxis in high-risk patients undergoing gynecological laparoscopic surgery: a prospective, randomized, double-blind, dose-response and placebo-controlled study.

Science.gov (United States)

Joo, Jin; Park, Yong Gyu; Baek, Jungwon; Moon, Young Eun

2015-07-08

Low-dose haloperidol is known to be effective for the prevention of postoperative nausea and vomiting (PONV). However, precise dose-response studies have not been completed, especially in patients at high risk for PONV who require combination therapy. This study sought to identify which dose of haloperidol 1mg or 2mg could be combined with dexamethasone without adverse effects in high-risk patients undergoing gynecological laparoscopic surgery. Female adults (n = 150) with three established PONV risk factors based on Apfel's score were randomized into one of three study groups. At the end of anesthesia, groups H0, H1, and H2 were given intravenous (IV) saline, haloperidol 1 mg, and haloperidol 2 mg, respectively. All patients were given dexamethasone 5 mg during the induction of anesthesia. The overall early (0-2 h) and late (2-24 h) incidences of nausea, vomiting, rescue anti-emetic administration, pain, and adverse effects (cardiac arrhythmias and extrapyramidal effects) were assessed postoperatively. The sedation score was recorded in the postanesthesia care unit (PACU). The total incidence of PONV over 24 h was significantly lower in groups H1 (29 %) and H2 (24 %) than in group H0 (54 %; P = 0.003), but there was no significant difference between groups H1 and H2. In the PACU, group H2 had a higher sedation score than groups H1 and H0 (P haloperidol was equally effective as 2 mg in terms of preventing PONV with the less sedative effect. ClinicalTrials.gov ( NCT01639599 ).

Population Pharmacokinetic-Pharmacodynamic Modeling of Haloperidol in Patients With Schizophrenia Using Positive and Negative Syndrome Rating Scale

NARCIS (Netherlands)

Reddy, Venkatesh Pilla; Kozielska, Magdalena; Johnson, Martin; Mafirakureva, Nyashadzaishe; Vermeulen, An; Liu, Jing; de Greef, Rik; Rujescu, Dan; Groothuis, Geny M. M.; Danhof, Meindert; Proost, Johannes H.

2013-01-01

The aim of this study was to develop a pharmacokinetic-pharmacodynamic (PKPD) model that quantifies the efficacy of haloperidol, accounting for the placebo effect, the variability in exposure-response, and the dropouts. Subsequently, the developed model was utilized to characterize an effective

Positron emission tomography with ( sup 18 F)methylspiperone demonstrates D sub 2 dopamine receptor binding differences of clozapine and haloperidol

Energy Technology Data Exchange (ETDEWEB)

Karbe, H; Wienhard, K; Huber, M; Herholz, K; Heiss, W D [Klinik fuer Neurologie, Univ. of Koeln, Koeln (Germany); Hamacher, K; Coenen, H H; Stoecklin, G [Inst. fuer Chemie 1, Forschungszentrum Juelich Gmbh (Germany); Loevenich, A [Klinik fuer Psychiatrie, Univ. of Koeln, Koeln (Germany)

1991-01-01

Four schizophrenic patients were investigated with dynamic positron emission tomography (PET) using ({sup 18}F)fluorodeoxyglucose (FDG) and ({sup 18}F)methylspiperone (MSP) as tracers. Two schizophrenics were on haloperidol therapy at the time of MSP PET. The other two schizophrenics were treated with clozapine, in one of them MSP PET was carried out twice with different daily doses (100 mg and 450mg respectively). Neuroleptic serum levels were measured in all patients. Results were compared with MSP PET of two drugfree male control subjects and with a previous fluoroethylspiperone (FESP) study of normals. Three hours after tracer injection specific binding of MSP was observed in the striatum in all cases. The striatum to cerebellum ratio was used to estimate the degree of neuroleptic-caused striatal D{sub 2} dopamine receptor occupancy. In the haloperidol treated patients MSP binding was significantly decreased, whereas in the clozapine treated patients striatum to cerebellum ratio was normal. Even the increase of clozapine dose in the same patient had no influence on this ratio. Despite the smaller number of patients the study shows for the first time in humans that striatal MSP binding reflects the different D{sub 2} dopamine receptor affinities of clozapine and haloperidol. (authors).

Electrochemical mechanism and kinetics studies of haloperidol and its assay in commercial formulations

International Nuclear Information System (INIS)

Ribeiro, Francisco W.P.; Soares, Janete E.S.; Becker, Helena; De Souza, Djenaine; Lima-Neto, Pedro de; Correia, Adriana N.

2011-01-01

The kinetics and mechanism for electrochemical reduction of haloperidol, a psychotherapeutic drug used in the treatment of schizophrenia, were studied using square wave and cyclic voltammetries allied to a hanging mercury drop electrode. The experimental and voltammetric parameters were optimized at 0.04 mol L -1 Brinton-Robinson buffer (pH 10), with a pulse potential frequency of 100 s -1 , a pulse amplitude of 30 mV and scan increment of 2 mV. Two well-defined peaks were observed, which exhibited properties of fast electron transfer with a strong adsorption process of reactants and products on the electrode surface. The first peak was related to a fast and reversible anion-radical formation originating from the reduction of the carbonyl group, and the second was related to the irreversible reduction of the anion-radical previously formed. Analytical parameters such as: linearity range, equation of the analytical curves, correlation coefficients, detection and quantification limits, recovery efficiency, and relative standard deviation for intraday and interday were compared to similar results obtained by use of the UV-vis spectrophotometry technique, and the analytical results obtained in commercial formulations show that the voltammetric procedure using a hanging mercury drop electrode is suitable for analyzing haloperidol in complex commercial formulation samples.

Electrochemical mechanism and kinetics studies of haloperidol and its assay in commercial formulations

Energy Technology Data Exchange (ETDEWEB)

Ribeiro, Francisco W.P. [Departamento de Quimica Analitica e Fisico-Quimica, Centro de Ciencias, Universidade Federal do Ceara, Bloco 940 Campus do Pici 60455-970, Fortaleza, CE (Brazil); Soares, Janete E.S. [Departamento de Farmacia, Faculdade de Farmacia, Odontologia e Enfermagem, Universidade Federal do Ceara, Rua Capitao Francisco Pedro, 1210 Rodolfo Teofilo 60430-370, Fortaleza, CE (Brazil); Becker, Helena; De Souza, Djenaine; Lima-Neto, Pedro de [Departamento de Quimica Analitica e Fisico-Quimica, Centro de Ciencias, Universidade Federal do Ceara, Bloco 940 Campus do Pici 60455-970, Fortaleza, CE (Brazil); Correia, Adriana N., E-mail: adriana@ufc.b [Departamento de Quimica Analitica e Fisico-Quimica, Centro de Ciencias, Universidade Federal do Ceara, Bloco 940 Campus do Pici 60455-970, Fortaleza, CE (Brazil)

2011-02-01

The kinetics and mechanism for electrochemical reduction of haloperidol, a psychotherapeutic drug used in the treatment of schizophrenia, were studied using square wave and cyclic voltammetries allied to a hanging mercury drop electrode. The experimental and voltammetric parameters were optimized at 0.04 mol L{sup -1} Brinton-Robinson buffer (pH 10), with a pulse potential frequency of 100 s{sup -1}, a pulse amplitude of 30 mV and scan increment of 2 mV. Two well-defined peaks were observed, which exhibited properties of fast electron transfer with a strong adsorption process of reactants and products on the electrode surface. The first peak was related to a fast and reversible anion-radical formation originating from the reduction of the carbonyl group, and the second was related to the irreversible reduction of the anion-radical previously formed. Analytical parameters such as: linearity range, equation of the analytical curves, correlation coefficients, detection and quantification limits, recovery efficiency, and relative standard deviation for intraday and interday were compared to similar results obtained by use of the UV-vis spectrophotometry technique, and the analytical results obtained in commercial formulations show that the voltammetric procedure using a hanging mercury drop electrode is suitable for analyzing haloperidol in complex commercial formulation samples.

Vitamin E and essential polyunsaturated fatty acids supplementation in schizophrenia patients treated with haloperidol.

Science.gov (United States)

Bošković, Marija; Vovk, Tomaž; Koprivšek, Jure; Plesničar, Blanka Kores; Grabnar, Iztok

2016-05-01

Previously, oxidative damage has been associated with severity of clinical symptoms and supplementation with antioxidants and essential polyunsaturated fatty acids (EPUFAs) was proposed to have beneficial effects in schizophrenia. We evaluated the effects of supplementation with EPUFAs and vitamin E in patients treated with haloperidol depot injection. This was a double-blind randomized placebo-controlled study with four arms (Placebo, vitamin E, EPUFAs, and vitamin E + EPUFAs). Biomarkers of oxidative stress, neurochemistry, psychopathology, and extrapyramidal symptoms were assessed at baseline and after 4 months. In EPUFAs group of patients, reduced glutathione concentration was increased compared to placebo. Concentration of oxidized glutathione was decreased in patients receiving vitamin E. In addition, compared to placebo a non-significant trend of increased activity of catalase and superoxide dismutase was observed in all three treatment groups. Patients receiving vitamin E experienced less motor retardation. No difference in extrapyramidal symptoms was found. Our study indicates that supplementation with vitamin E and EPUFAs may improve the antioxidative defense, especially glutathione system, while there is no major effect on symptoms severity. Supplemental treatment with EPUFAs and vitamin E in schizophrenia patients treated with haloperidol is potentially beneficial and a larger independent study appears warranted.

Coenzyme Q10 does not prevent oral dyskinesias induced by long-term haloperidol treatment of rats

DEFF Research Database (Denmark)

OA, Andreassen; Weber, Christine; HA, Jorgensen

1999-01-01

dyskinesias in rats, a putative analogue to human TD, could be prevented by the antioxidant coenzyme Q10 (CoQ10). Rats received 16 weeks of treatment with haloperidol decanoate (HAL) IM alone or together with orally administered CoQ10, and the behavior was recorded during and after treatment. HAL...

Effect of Environmental Cues on Behavioral Efficacy of Haloperidol, Olanzapine and Clozapine in Rats

Science.gov (United States)

Sun, Tao; Liu, Xinfeng; Li, Ming

2014-01-01

Previous studies have reported that context can powerfully modulate the inhibitory effect of an antipsychotic drug on phencyclidine (PCP)-induced hyperlocomotion (a behavioral test used to evaluate putative antipsychotic drugs). The present study investigated the experimental conditions under which environmental stimuli exert their influence through associative conditioning processes. Experiment 1 examined the extent to which prior antipsychotic treatment in the home cages affected a drug’s ability to inhibit PCP-induced hyperlocomotion in a novel motor activity test apparatus. Five days of repeated haloperidol (0.05 mg/kg, sc) and olanzapine (2.0 mg/kg, sc) treatment in the home cages still potentiated their inhibition of PCP-induced hyperlocomotion (i.e. sensitization) assessed in a new environment, whereas the clozapine (10.0 mg/kg, sc) treatment enhanced the development of clozapine tolerance, indicating a lack of environmental modulation of antipsychotic efficacy. Experiment 2 assessed the impact of different numbers of antipsychotic administrations in either the home environment or test environment (e.g. 4, 2 or 0) on a drug’s ability to inhibit PCP-induced hyperlocomotion. Repeated administration of clozapine (5.0 mg/kg, sc) or olanzapine (1.0 mg/kg, sc) for 4 consecutive days, regardless of where these treatments occurred, caused a similar level of inhibition on PCP-induced hyperlocomotion. However, 4-day haloperidol (0.03 mg/kg, sc) treatment in the test apparatus caused a significant higher inhibition than 4-day home cage treatment. Thus, more exposures to the test environment under the influence of haloperidol (but not clozapine or olanzapine) cause a stronger inhibition than fewer exposures, indicating a strong environmental modulation. Collectively, these findings suggest that prior antipsychotic treatment in one environment could alter later antipsychotic-like response assessed in a different environment under certain test conditions. Therefore

Naloxone-sensitive, haloperidol-sensitive, [3H](+)SKF-10047-binding protein partially purified from rat liver and rat brain membranes: an opioid/sigma receptor?

Science.gov (United States)

Tsao, L I; Su, T P

1997-02-01

A naloxone-sensitive, haloperidol-sensitive, [3H](+)SKF-10047-binding protein was partially purified from rat liver and rat brain membranes in an affinity chromatography originally designed to purify sigma receptors. Detergent-solubilized extracts from membranes were adsorbed to Sephadex G-25 resin containing an affinity ligand for sigma receptors: N-(2- 3,4-dichlorophenyl]ethyl)-N-(6-aminohexyl)-(2-[1-pyrrolidinyl]) ethylamine (DAPE). After eluting the resin with haloperidol, a protein that bound [3H](+)SKF-10047 was detected in the eluates. However, the protein was not the sigma receptor. [3H](+)SKF-10047 binding to the protein was inhibited by the following compounds in the order of decreasing potency: (+)pentazocine > (-) pentazocine > (+/-)cyclazocine > (-)morphine > (-)naloxone > haloperidol > (+)SKF-10047 > DADLE > (-)SKF-10047. Further, the prototypic sigma receptor ligands, such as 1,3-di-o-tolylguanidine (DTG), (+)3-PPP, and progesterone, bound poorly to the protein. Tryptic digestion and heat treatment of the affinity-purified protein abolished radioligand binding. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS/PAGE) of the partially-purified protein from the liver revealed a major diffuse band with a molecular mass of 31 kDa, a polypeptide of 65 kDa, and another polypeptide of > 97 kDa. This study demonstrates the existence of a novel protein in the rat liver and rat brain which binds opioids, benzomorphans, and haloperidol with namomolar affinity. The protein resembles the opioid/sigma receptor originally proposed by Martin et al. [(1976): J. Pharmacol. Exp. Ther., 197:517-532.]. A high degree of purification of this protein has been achieved in the present study.

Oral haloperidol or olanzapine intake produces distinct and region-specific increase in cannabinoid receptor levels that is prevented by high fat diet.

Science.gov (United States)

Delis, Foteini; Rosko, Lauren; Shroff, Aditya; Leonard, Kenneth E; Thanos, Panayotis K

2017-10-03

Clinical studies show higher levels of cannabinoid CB1 receptors (CB1R) in the brain of schizophrenic patients while preclinical studies report a significant functional interaction between dopamine D2 receptors and CB1Rs as well as an upregulation of CB1Rs after antipsychotic treatment. These findings prompted us to study the effects of chronic oral intake of a first and a second generation antipsychotic, haloperidol and olanzapine, on the levels and distribution of CB1Rs in the rat brain. Rats consumed either regular chow or high-fat food and drank water, haloperidol drinking solution (1.5mg/kg), or olanzapine drinking solution (10mg/kg) for four weeks. Motor and cognitive functions were tested at the end of treatment week 3 and upon drug discontinuation. Two days after drug discontinuation, rats were euthanized and brains were processed for in vitro receptor autoradiography. In chow-fed animals, haloperidol and olanzapine increased CB1R levels in the basal ganglia and the hippocampus, in a similar, but not identical pattern. In addition, olanzapine had unique effects in CB1R upregulation in higher order cognitive areas, in the secondary somatosensory cortex, in the visual and auditory cortices and the geniculate nuclei, as well as in the hypothalamus. High fat food consumption prevented antipsychotic-induced increase in CB1R levels in all regions examined, with one exception, the globus pallidus, in which they were higher in haloperidol-treated rats. The results point towards the hypothesis that increased CB1R levels could be a confounding effect of antipsychotic medication in schizophrenia that is circumveneted by high fat feeding. Copyright © 2017 Elsevier Inc. All rights reserved.

A COMPARATIVE STUDY OF ORAL OLANZAPINE AND ORAL HALOPERIDOL ON GLUCOSE TOLERANCE LEVELS IN PATIENTS WITH SCHIZOPHRENIA

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G N S Sangeetha Lakshmi

2015-08-01

Full Text Available Background: Schizophrenia is a mental disorder characterized by persistent defects in the perception, thinking or the expression of reality. The term “schizophrenia” translates roughly as “shattered mind,” and comes from the Greek (schizo, “to split” or “to divide” and (phrēn, “mind”. Material and Methods: The study was designed to be a prospective control study. Schizophrenic patients taking Olanzapine and Haloperidol were selected and follow up at three weeks and six weeks was done. Results: In this prospective control study, Olanzapine and Haloperidol were associated with an increase in Blood Glucose Levels. The mean changes in Glucose remained within clinically normal range in this six week study. Conclusion: Antipsychotic treatmemt leads to the development of Diabetes mellitus in a significant 10.1% of patients within 6 weeks. Given the serious implications for morbidity and mortality attributable to diabetes mellitus, clinicians need to be aware of these risk factors when treating patients with chronic schizophrenia

Acute administration of haloperidol does not influence 123I-FP-CIT binding to the dopamine transporter

NARCIS (Netherlands)

Booij, Jan; van Loon, Guus; de Bruin, Kora; Voorn, Pieter

2014-01-01

A recent (123)I-FP-CIT ((123)-I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane) SPECT study on rats suggested that a single 1 mg/kg dose of the antipsychotic haloperidol induces enough dopamine release to compete with (123)I-FP-CIT for binding to the dopamine transporter. Taking into

Haloperidol em doenças mentais: Contribuição clínica

Directory of Open Access Journals (Sweden)

Waltek N. Cardo

1965-03-01

Full Text Available Após rápido relato dos principais trabalhos publicados a respeito do Haloperidol, os autores relatam sua experiência no tratamento de 82 pacientes hospitalizados, em sua maioria esquizofrênicos. O tratamento foi iniciado, em geral, com a dose diária de 1 mg, aumentada, gradualmente, até dose diária máxima variável entre 3 e 16 mg. Concluíram ter o Haloperidol nítida ação sedativa e alucinolítica e ser principalmente indicado no tratamento dos casos de mania e esquizofrenia forma paranóide, como também em outras psicoses com predominância de agitação psicomotora e/ou síndrome delirante-alucinatória. As formas hebefrênica e catatônica da esquizofrenia também se beneficiam com o tratamento. Quanto aos efeitos secundários, a maioria dos pacientes apresentou síndrome de impregnação (síndrome acineto-hipertônica, quase todos insônia, alguns acatisia; apenas em um caso foram assinalados distúrbios neurovegetativos intensos para o lado do aparelho cardiovascular. Foram assinaladas alterações eletrencefalográficas difusas que desapareceram após o término do tratamento.

Comparison of intramuscular olanzapine, orally disintegrating olanzapine tablets, oral risperidone solution, and intramuscular haloperidol in the management of acute agitation in an acute care psychiatric ward in Taiwan.

Science.gov (United States)

Hsu, Wen-Yu; Huang, Si-Sheng; Lee, Bo-Shyan; Chiu, Nan-Ying

2010-06-01

The purpose of this study was to compare efficacy and safety among intramuscular olanzapine, intramuscular haloperidol, orally disintegrating olanzapine tablets, and oral risperidone solution for agitated patients with psychosis during the first 24 hours of treatment in an acute care psychiatric ward. Forty-two inpatients from an acute care psychiatric ward of a medical center in central Taiwan were enrolled. They were randomly assigned to 1 of the 4 treatment groups (10-mg intramuscular olanzapine, 10-mg olanzapine oral disintegrating tablet, 3-mg oral risperidone solution, or 7.5-mg intramuscular haloperidol). Agitation was measured by using the excited component of the Positive and Negative Syndrome Scale (PANSS-EC), the Agitation-Calmness Evaluation Scale, and the Clinical Global Impression--Severity Scale during the first 24 hours. There were significant differences in the PANSS-EC total scores for the 4 intervention groups at 15, 30, 45, 60, 75, and 90 minutes after the initiation of treatment. More significant differences were found early in the treatment. In the post hoc analysis, the patients who received intramuscular olanzapine or orally disintegrating olanzapine tablets showed significantly greater improvement in PANSS-EC scores than did patients who received intramuscular haloperidol at points 15, 30, 45, 60, 75, and 90 minutes after injection. These findings suggest that intramuscular olanzapine, orally disintegrating olanzapine tablets, and oral risperidone solution are as effective treatments as intramuscular haloperidol for patients with acute agitation. Intramuscular olanzapine and disintegrating olanzapine tablets are more effective than intramuscular haloperidol in the early phase of the intervention. There is no significant difference in effectiveness among intramuscular olanzapine, orally disintegrating olanzapine tablets, and oral risperidone solution.

N-n-butyl haloperidol iodide protects cardiomyocytes against hypoxia/reoxygenation injury by inhibiting autophagy.

Science.gov (United States)

Wang, Bin; Zhong, Shuping; Zheng, Fuchun; Zhang, Yanmei; Gao, Fenfei; Chen, Yicun; Lu, Binger; Xu, Han; Shi, Ganggang

2015-09-22

N-n-butyl haloperidol iodide (F2), a novel compound derived from haloperidol, protects against the damaging effects of ischemia/reperfusion (I/R) injury in vitro and in vivo. In this study, we hypothesized the myocardial protection of F2 on cardiomyocyte hypoxia/reoxygenation (H/R) injury is mediated by inhibiting autophagy in H9c2 cells. The degree of autophagy by treatment with F2 exposed to H/R in H9c2 cell was characterized by monodansylcadaverine, transmission electron microscopy, and expression of autophagy marker protein LC3. Our results indicated that treatment with F2 inhibited autophagy in H9c2 cells exposed to H/R. 3-methyladenine, an inhibitor of autophagy, suppressed H/R-induced autophagy, and decreased apoptosis, whereas rapamycin, a classical autophagy sensitizer, increased autophagy and apoptosis. Mechanistically, macrophage migration inhibitory factor (MIF) was inhibited by F2 treatment after H/R. Accordingly, small interfering RNA (siRNA)-mediated MIF knockdown decreased H/R-induced autophagy. In summary, F2 protects cardiomyocytes during H/R injury through suppressing autophagy activation. Our results provide a new mechanistic insight into a functional role of F2 against H/R-induced cardiomyocyte injury and death.

Carrier-added and no-carrier-added syntheses of [18F]spiroperidol and [18F]haloperidol

International Nuclear Information System (INIS)

Kilbourn, M.R.; Welch, M.J.; Dence, C.S.; Tewson, T.J.; Saji, H.; Maeda, M.

1984-01-01

Syntheses of [ 18 F]haloperidol and [ 18 F]spiroperidol in both no-carrier-added and carrier-added forms have been accomplished. The no-carrier-added [ 18 F]butyrophenone neuroleptics were prepared in low ( 18 F-neuroleptics were prepared in better (5-17%) yields by 18 F-for- 19 F nucleophilic aromatic substitution. The preparation of all synthetic precursors, and procedures for radiolabeling are fully described. (author)

Duration of surgical-orthodontic treatment.

Science.gov (United States)

Häll, Birgitta; Jämsä, Tapio; Soukka, Tero; Peltomäki, Timo

2008-10-01

To study the duration of surgical-orthodontic treatment with special reference to patients' age and the type of tooth movements, i.e. extraction vs. non-extraction and intrusion before or extrusion after surgery to level the curve of Spee. The material consisted files of 37 consecutive surgical-orthodontic patients. The files were reviewed and gender, diagnosis, type of malocclusion, age at the initiation of treatment, duration of treatment, type of tooth movements (extraction vs. non-extraction and levelling of the curve of Spee before or after operation) and type of operation were retrieved. For statistical analyses two sample t-test, Kruskal-Wallis and Spearman rank correlation tests were used. Mean treatment duration of the sample was 26.8 months, of which pre-surgical orthodontics took on average 17.5 months. Patients with extractions as part of the treatment had statistically and clinically significantly longer treatment duration, on average 8 months, than those without extractions. No other studied variable seemed to have an impact on the treatment time. The present small sample size prevents reliable conclusions to be made. However, the findings suggest, and patients should be informed, that extractions included in the treatment plan increase chances of longer duration of surgical-orthodontic treatment.

Synthesis and tissue distribution studies of two novel esters of haloperidol and the application of radiolabelling techniques using short-lived radionuclides in the study of the deposition characteristics of suspended aerosol particles

International Nuclear Information System (INIS)

Smith, M.F.

1982-01-01

In the present work, the Schotten-Baumann reaction conditions were modified to esterify the tertiary hydroxyl group of haloperidol. The rapid synthesis (less than 20 min) makes this procedure applicable to the preparation of esters of haloperidol containing fluorine-18 (t/sup (1/2)/ 110 min), a γ-emitting radioisotope useful in external scintigraphy. In vivo distribution studies of the synthesized tritiated esters and haloperidol in the rat demonstrated that neither ester prodrug achieved overall higher brain concentration levels than haloperidol. In this study, radiotracer techniques were developed to examine parameters that characterize pressurized aerosols designed to utilize insoluble particles suspended in the aerosol formulation. The suspended micro-aggregated bovine albumin microspheres were labelled with iodine-131 (t/sup (1/2)/ 8 days). The techniques developed illustrate the use of short-lived radionuclides for: 1) quantitation of each metered dose; 2) characterization of particle size distribution by the aerosol; and 3) determination of the extent of deposition of the particles in the aerosol and all of its components

Two Sudden and Unexpected Deaths of Patients with Schizophrenia Associated with Intramuscular Injections of Antipsychotics and Practice Guidelines to Limit the Use of High Doses of Intramuscular Antipsychotics

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Nasratullah Wahidi

2016-01-01

Full Text Available Intravenous haloperidol has been associated with torsades de pointes (TdP. These two sudden deaths were probable adverse drug reactions (ADRs following intramuscular (IM antipsychotics. The autopsies described lack of heart pathology and were highly compatible with the possibility of TdP in the absence of risk factors other than the accumulation of antipsychotics with a high serum peak after the last injection, leading to death within hours. The first case was a 27-year-old African-American male with schizophrenia but no medical issues. His death was probably caused by repeated IM haloperidol injections of 10 mg (totaling 35 mg in 2 days. The second case involves a 42-year-old African-American female with metabolic syndrome. Her probable cause of death was the last ziprasidone IM injection of 20 mg in addition to (1 three extra haloperidol doses (2 hours before the ziprasidone injection, 5 mg oral haloperidol; approximately 21 hours earlier, 5 mg oral haloperidol; and 2 days prior, one 10 mg IM haloperidol injection, (2 10 mg/day of scheduled oral haloperidol for 6 days before death, and (3 a long-acting paliperidone injection of 156 mg 18 days before death. The study of haloperidol glucuronidation and its impairment in some African-Americans is urgently recommended.

[123I]Iodobenzamide binding to the rat dopamine D2 receptor in competition with haloperidol and endogenous dopamine - an in vivo imaging study with a dedicated small animal SPECT

International Nuclear Information System (INIS)

Nikolaus, Susanne; Larisch, Rolf; Wirrwar, Andreas; Jamdjeu-Noune, Marlyse; Antke, Christina; Beu, Markus; Mueller, Hans-Wilhelm; Schramm, Nils

2005-01-01

This study assessed [ 123 I]iodobenzamide binding to the rat dopamine D 2 receptor in competition with haloperidol and endogenous dopamine using a high-resolution small animal SPECT. Subsequent to baseline quantifications of D 2 receptor binding, imaging studies were performed on the same animals after pre-treatment with haloperidol and methylphenidate, which block D 2 receptors and dopamine transporters, respectively. Striatal baseline equilibrium ratios (V 3 '' ) of [ 123 I]iodobenzamide binding were 1.42±0.31 (mean±SD). After pre-treatment with haloperidol and methylphenidate, V 3 '' values decreased to 0.54±0.46 (p 123 I]iodobenzamide binding induced by pre-treatment with haloperidol reflects D 2 receptor blockade, whereas the decrease in receptor binding induced by pre-treatment with methylphenidate can be interpreted in terms of competition between [ 123 I]IBZM and endogenous dopamine. Findings show that multiple in vivo measurements of [ 123 I]iodobenzamide binding to D 2 receptors in competition with exogenous and endogenous ligands are feasible in the same animal. This may be of future relevance for the in vivo evaluation of novel radioligands as well as for studying the interrelations between pre- and/or postsynaptic radioligand binding and different levels of endogenous dopamine. (orig.)

Injections of the selective adenosine A2A antagonist MSX-3 into the nucleus accumbens core attenuate the locomotor suppression induced by haloperidol in rats.

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Ishiwari, Keita; Madson, Lisa J; Farrar, Andrew M; Mingote, Susana M; Valenta, John P; DiGianvittorio, Michael D; Frank, Lauren E; Correa, Merce; Hockemeyer, Jörg; Müller, Christa; Salamone, John D

2007-03-28

There is considerable evidence of interactions between adenosine A2A receptors and dopamine D2 receptors in striatal areas, and antagonists of the A2A receptor have been shown to reverse the motor effects of DA antagonists in animal models. The D2 antagonist haloperidol produces parkinsonism in humans, and also induces motor effects in rats, such as suppression of locomotion. The present experiments were conducted to study the ability of the adenosine A2A antagonist MSX-3 to reverse the locomotor effects of acute or subchronic administration of haloperidol in rats. Systemic (i.p.) injections of MSX-3 (2.5-10.0 mg/kg) were capable of attenuating the suppression of locomotion induced by either acute or repeated (i.e., 14 day) administration of 0.5 mg/kg haloperidol. Bilateral infusions of MSX-3 directly into the nucleus accumbens core (2.5 microg or 5.0 microg in 0.5 microl per side) produced a dose-related increase in locomotor activity in rats treated with 0.5 mg/kg haloperidol either acutely or repeatedly. There were no overall significant effects of MSX-3 infused directly into the dorsomedial nucleus accumbens shell or the ventrolateral neostriatum. These results indicate that antagonism of adenosine A2A receptors can attenuate the locomotor suppression produced by DA antagonism, and that this effect may be at least partially mediated by A2A receptors in the nucleus accumbens core. These studies suggest that adenosine and dopamine systems interact to modulate the locomotor and behavioral activation functions of nucleus accumbens core.

Enhanced striatial 3H-spiroperidol binding induced by chronic haloperidol treatment inhibited by peptides administered during the withdrawal phase

International Nuclear Information System (INIS)

Bhargava, H.N.

1984-01-01

Chronic intragastric administration of haloperidol (1.5 mg/kg/day) for 21 days followed by a 3-day withdrawal period resulted in the development of enhanced locomotor activity response to apomorphine, and an increase in the number of binding sites for 3 H-spiroperidol in the striatal membranes of the rat brain. Subcutaneous administration of Pro-Leu-Gly-NH 2 or cyclo-(Leu-Gly) in doses of 2 mg/kg/day given for 3-days after termination of haloperidol treatment inhibited the enhanced response to apomorphine, as well as the increases in the number of 3 H-spiroperidol binding sites in the striatum. If indeed, the supersensitivity of striatal dopamine receptors is one of the mechanisms in the development of tardive dyskinesia symptoms, the present results suggest that the above peptides may be helpful in ameliorating some of the symptoms of tardive dyskinesia induced by neuroleptic drugs. 31 references, 3 figures

Continuous Preparation of 1:1 Haloperidol-Maleic Acid Salt by a Novel Solvent-Free Method Using a Twin Screw Melt Extruder.

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Lee, Hung Lin; Vasoya, Jaydip M; Cirqueira, Marilia de Lima; Yeh, Kuan Lin; Lee, Tu; Serajuddin, Abu T M

2017-04-03

Salts are generally prepared by acid-base reaction in relatively large volumes of organic solvents, followed by crystallization. In this study, the potential for preparing a pharmaceutical salt between haloperidol and maleic acid by a novel solvent-free method using a twin-screw melt extruder was investigated. The pH-solubility relationship between haloperidol and maleic acid in aqueous medium was first determined, which demonstrated that 1:1 salt formation between them was feasible (pH max 4.8; salt solubility 4.7 mg/mL). Extrusion of a 1:1 mixture of haloperidol and maleic acid at the extruder barrel temperature of 60 °C resulted in the formation of a highly crystalline salt. The effects of operating temperature and screw configuration on salt formation were also investigated, and those two were identified as key processing parameters. Salts were also prepared by solution crystallization from ethyl acetate, liquid-assisted grinding, and heat-assisted grinding and compared with those obtained by melt extrusion by using DSC, PXRD, TGA, and optical microscopy. While similar salts were obtained by all methods, both melt extrusion and solution crystallization yielded highly crystalline materials with identical enthalpies of melting. During the pH-solubility study, a salt hydrate form was also identified, which, upon heating, converted to anhydrate similar to that obtained by other methods. There were previous reports of the formation of cocrystals, but not salts, by melt extrusion. 1 H NMR and single-crystal X-ray diffraction confirmed that a salt was indeed formed in the present study. The haloperidol-maleic acid salt obtained was nonhygroscopic in the moisture sorption study and converted to the hydrate form only upon mixing with water. Thus, we are reporting for the first time a relatively simple and solvent-free twin-screw melt extrusion method for the preparation of a pharmaceutical salt that provides material comparable to that obtained by solution

A tailored implementation strategy to reduce the duration of intravenous antibiotic treatment in community-acquired pneumonia: a controlled before-and-after study.

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Engel, M F; Bruns, A H W; Hulscher, M E J L; Gaillard, C A J M; Sankatsing, S U C; Teding van Berkhout, F; Emmelot-Vonk, M H; Kuck, E M; Steeghs, M H M; den Breeijen, J H; Stellato, R K; Hoepelman, A I M; Oosterheert, J J

2014-11-01

We previously showed that 40 % of clinically stable patients hospitalised for community-acquired pneumonia (CAP) are not switched to oral therapy in a timely fashion because of physicians' barriers. We aimed to decrease this proportion by implementing a novel protocol. In a multi-centre controlled before-and-after study, we evaluated the effect of an implementation strategy tailored to previously identified barriers to an early switch. In three Dutch hospitals, a protocol dictating a timely switch strategy was implemented using educational sessions, pocket reminders and active involvement of nursing staff. Primary outcomes were the proportion of patients switched timely and the duration of intravenous antibiotic therapy. Length of hospital stay (LOS), patient outcome, education effects 6 months after implementation and implementation costs were secondary outcomes. Statistical analysis was performed using mixed-effects models. Prior to implementation, 146 patients were included and, after implementation, 213 patients were included. The case mix was comparable. The implementation did not change the proportion of patients switched on time (66 %). The median duration of intravenous antibiotic administration decreased from 4 days [interquartile range (IQR) 2-5] to 3 days (IQR 2-4), a decrease of 21 % [95 % confidence interval (CI) 11 %; 30 %) in the multi-variable analysis. LOS and patient outcome were comparable before and after implementation. Forty-three percent (56/129) of physicians attended the educational sessions. After 6 months, 24 % (10/42) of the interviewed attendees remembered the protocol's main message. Cumulative implementation costs were 5,798 (20/reduced intravenous treatment day). An implementation strategy tailored to previously identified barriers reduced the duration of intravenous antibiotic administration in hospitalised CAP patients by 1 day, at minimal cost.

Hydrogen Bonding: Between Strengthening the Crystal Packing and Improving Solubility of Three Haloperidol Derivatives.

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Saluja, Hardeep; Mehanna, Ahmed; Panicucci, Riccardo; Atef, Eman

2016-06-01

The purpose of this study is to confirm the impact of polar functional groups on inter and intra-molecular hydrogen bonding in haloperidol (HP) and droperidol (DP) and, hence, their effects on dissolution using a new approach. To confirm our theory, a new molecule: deshydroxy-haloperidol (DHP) was designed and its synthesis was requested from a contract laboratory. The molecule was then studied and compared to DP and HP. Unlike DHP, both the HP and DP molecules have hydrogen donor groups, therefore, DHP was used to confirm the relative effects of the hydrogen donor group on solubility and crystal packing. The solid dispersions of the three structurally related molecules: HP, DP, and DHP were prepared using PVPK30, and characterized using XRPD and IR. A comparative dissolution study was carried out in aqueous medium. The absence of a hydrogen bonding donor group in DHP resulted in an unexpected increase in its aqueous solubility and dissolution rate from solid dispersion, which is attributed to weaker crystal pack. The increased dissolution rate of HP and DP from solid dispersions is attributed to drug-polymer hydrogen bonding that interferes with the drug-drug intermolecular hydrogen bonding and provides thermodynamic stability of the dispersed drug molecules. The drug-drug intermolecular hydrogen bond is the driving force for precipitation and crystal packing.

Pharmacokinetic considerations and recommendations in palliative care, with focus on morphine, midazolam and haloperidol.

Science.gov (United States)

Franken, L G; de Winter, B C M; van Esch, H J; van Zuylen, L; Baar, F P M; Tibboel, D; Mathôt, R A A; van Gelder, T; Koch, B C P

2016-06-01

A variety of medications are used for symptom control in palliative care, such as morphine, midazolam and haloperidol. The pharmacokinetics of these drugs may be altered in these patients as a result of physiological changes that occur at the end stage of life. This review gives an overview of how the pharmacokinetics in terminally ill patients may differ from the average population and discusses the effect of terminal illness on each of the four pharmacokinetic processes absorption, distribution, metabolism, and elimination. Specific considerations are also given for three commonly prescribed drugs in palliative care: morphine, midazolam and haloperidol). The pharmacokinetics of drugs in terminally ill patients can be complex and limited evidence exists on guided drug use in this population. To improve the quality of life of these patients, more knowledge and more pharmacokinetic/pharmacodynamics studies in terminally ill patients are needed to develop individualised dosing guidelines. Until then knowledge of pharmacokinetics and the physiological changes that occur in the final days of life can provide a base for dosing adjustments that will improve the quality of life of terminally ill patients. As the interaction of drugs with the physiology of dying is complex, pharmacological treatment is probably best assessed in a multi-disciplinary setting and the advice of a pharmacist, or clinical pharmacologist, is highly recommended.

Hydrogen Bonding: Between Strengthening the Crystal Packing and Improving Solubility of Three Haloperidol Derivatives

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Hardeep Saluja

2016-06-01

Full Text Available The purpose of this study is to confirm the impact of polar functional groups on inter and intra-molecular hydrogen bonding in haloperidol (HP and droperidol (DP and, hence, their effects on dissolution using a new approach. To confirm our theory, a new molecule: deshydroxy-haloperidol (DHP was designed and its synthesis was requested from a contract laboratory. The molecule was then studied and compared to DP and HP. Unlike DHP, both the HP and DP molecules have hydrogen donor groups, therefore, DHP was used to confirm the relative effects of the hydrogen donor group on solubility and crystal packing. The solid dispersions of the three structurally related molecules: HP, DP, and DHP were prepared using PVPK30, and characterized using XRPD and IR. A comparative dissolution study was carried out in aqueous medium. The absence of a hydrogen bonding donor group in DHP resulted in an unexpected increase in its aqueous solubility and dissolution rate from solid dispersion, which is attributed to weaker crystal pack. The increased dissolution rate of HP and DP from solid dispersions is attributed to drug-polymer hydrogen bonding that interferes with the drug-drug intermolecular hydrogen bonding and provides thermodynamic stability of the dispersed drug molecules. The drug-drug intermolecular hydrogen bond is the driving force for precipitation and crystal packing.

Haloperidol augmentation of fluvoxamine in skin picking disorder: a case report

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Luca Maria

2012-07-01

Full Text Available Abstract Introduction Compulsive skin picking, being part of the broader category of impulse control disorders, is considered a residual diagnosis in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. It is characterized by excessive scratching or picking of normal skin, or skin with minor surface irregularities, and occurs in 2% of patients attending dermatology clinics. Despite the clinical relevance of this disorder, no clear guidelines are available yet; clinical management is, therefore, compromised and the day-to-day clinical practice is burdened by difficulties. Studies on selective serotonin reuptake inhibitors and anti-epileptic drugs have provided limited results. The association between anti-depressants and anti-epileptics has been found to be beneficial in some impulse control disorders, but in skin picking no previous studies have been conducted on this pharmacological approach. There are very few reports on the efficacy of anti-psychotics in skin picking. Case presentation The therapeutic path described in this case report produced good results for a 59-year-old Caucasian woman. The first therapeutic approach, with fluvoxamine and oxcarbazepine was partially effective; then, the suspension of oxcarbazepine and haloperidol augmentation of fluvoxamine were adopted. After 10 weeks, a significant improvement of the disease was observed: the clinical picture and the associated symptoms were nearly solved. Conclusions To the best of our knowledge, this is the first article reporting the association of fluvoxamine and haloperidol in skin picking disorder. It might be useful to perform further research regarding the treatment of skin picking disorder: in clinical practice, several variables might limit the choice of certain drugs. Therefore, it would be useful for the clinician to be aware of other therapeutic options.

Degradation products of irradiated haloperidol: implications for the development of an implantible delivery system

Energy Technology Data Exchange (ETDEWEB)

Booker, J

1988-01-01

Haloperidol was chosen as a model compound to determine whether the degradation products created by sterilizing dose of gamma radiation would contaminate an implantible delivery device and be hazardous to the health of the person using it. Acrolein, chlorobenzene, and several other products were identified among the degradation products. They were quantitated and evaluated as being potentially dangerous. It is recommended that the development protocol for a radiation-sterilized, implantible drug include the identification and evaluation of the degradation products.

Degradation products of irradiated haloperidol: implications for the development of an implantible delivery system

International Nuclear Information System (INIS)

Booker, J.

1988-01-01

Haloperidol was chosen as a model compound to determine whether the degradation products created by sterilizing dose of gamma radiation would contaminate an implantible delivery device and be hazardous to the health of the person using it. Acrolein, chlorobenzene, and several other products were identified among the degradation products. They were quantitated and evaluated as being potentially dangerous. It is recommended that the development protocol for a radiation-sterilized, implantible drug include the identification and evaluation of the degradation products. (author)

Comparison between the efficacies of Risperidone with Haloperidol in the treatment of attention-deficit hyperactivity disorder (ADHD) among preschoolers: a randomized double-blind clinical trial.

Science.gov (United States)

Riahi, Forough; Tashakori, Ashraf; Abdi, Leila

2016-09-01

Attention-deficit hyperactivity disorder (ADHD) is a common psychiatric disease with a worldwide pooled prevalence of 5.29%. To compare the efficacy of Risperidone with Haloperidol in the treatment of attention-deficit hyperactivity disorder (ADHD) among 3- to 6-year-old children. In a 6-week double-blind clinical trial, the efficacy of Risperidone 0.5-2 mg with a dose of maximum Haloperidol 0.075 mg/kg was assessed in 39 children aged 3-6 years. This study was conducted at the Golestan Psychiatric Clinic (Ahvaz, Iran). Measurement tools included the Conners' Parent Rating Scale (CPRS-48), Children's Global Assessment Scale (CGAS), and the Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS). Data were analyzed using the Wilcoxon, Mann-Whitney, and Fisher's exact tests in the SPSS 19. During the 6 weeks, the decline in points was seen in Conner's rating scale and in ADHD-RS score in Risperidone and Haloperidol groups (pscale, an increase of performance in both groups for six weeks was statistically significant (pscales of ADHD-RS and CPRS-48, no statistically significant difference was observed between the two treatment groups; i.e., in terms of reducing the rate during weeks of two, four, and six (p>0.05). Haloperidol and Risperidone possibly can be an acceptable treatment choice in the ADHD treatment of 3- to 6-year-old children. The trial was registered at the Iranian Registry of Clinical Trials (http://www.irct.ir) with the Irct ID: IRCT2015082623766N1. This work was financially supported by grant (ref. no.: U-93130) from the vice chancellor for Research Affairs of Ahvaz Jundishapur University of Medical Sciences.

The effect of changes in core body temperature on the QT interval in beagle dogs: a previously ignored phenomenon, with a method for correction.

Science.gov (United States)

van der Linde, H J; Van Deuren, B; Teisman, A; Towart, R; Gallacher, D J

2008-08-01

Body core temperature (Tc) changes affect the QT interval, but correction for this has not been systematically investigated. It may be important to correct QT intervals for drug-induced changes in Tc. Anaesthetized beagle dogs were artificially cooled (34.2 degrees C) or warmed (42.1 degrees C). The relationship between corrected QT intervals (QTcV; QT interval corrected according to the Van de Water formula) and Tc was analysed. This relationship was also examined in conscious dogs where Tc was increased by exercise. When QTcV intervals were plotted against changes in Tc, linear correlations were observed in all individual dogs. The slopes did not significantly differ between cooling (-14.85+/-2.08) or heating (-13.12+/-3.46) protocols. We propose a correction formula to compensate for the influence of Tc changes and standardize the QTcV duration to 37.5 degrees C: QTcVcT (QTcV corrected for changes in core temperature)=QTcV-14 (37.5 - Tc). Furthermore, cooled dogs were re-warmed (from 34.2 to 40.0 degrees C) and marked QTcV shortening (-29%) was induced. After Tc correction, using the above formula, this decrease was abolished. In these re-warmed dogs, we observed significant increases in T-wave amplitude and in serum [K(+)] levels. No arrhythmias or increase in pro-arrhythmic biomarkers were observed. In exercising dogs, the above formula completely compensated QTcV for the temperature increase. This study shows the importance of correcting QTcV intervals for changes in Tc, to avoid misleading interpretations of apparent QTcV interval changes. We recommend that all ICH S7A, conscious animal safety studies should routinely measure core body temperature and correct QTcV appropriately, if body temperature and heart rate changes are observed.

Prehospital Agitation and Sedation Trial (PhAST): A Randomized Control Trial of Intramuscular Haloperidol versus Intramuscular Midazolam for the Sedation of the Agitated or Violent Patient in the Prehospital Environment.

Science.gov (United States)

Isenberg, Derek L; Jacobs, Dorian

2015-10-01

Violent patients in the prehospital environment pose a threat to health care workers tasked with managing their medical conditions. While research has focused on methods to control the agitated patient in the emergency department (ED), there is a paucity of data looking at the optimal approach to subdue these patients safely in the prehospital setting. Hypothesis This study evaluated the efficacy of two different intramuscular medications, midazolam and haloperidol, to determine their efficacy in sedating agitated patients in the prehospital setting. This was a prospective, randomized, observational trial wherein agitated patients were administered intramuscular haloperidol or intramuscular midazolam to control agitation. Agitation was quantified by the Richmond Agitation and Sedation Scale (RASS). Paramedics recorded the RASS and vital signs every five minutes during transport and again upon arrival to the ED. The primary outcome was mean time to achieve a RASS less than +1. Secondary outcomes included mean time for patients to return to baseline mental status and adverse events. Five patients were enrolled in each study group. In the haloperidol group, the mean time to achieve a RASS score of less than +1 was 24.8 minutes (95% CI, 8-49 minutes), and the mean time for the return of a normal mental status was 84 minutes (95% CI, 0-202 minutes). Two patients required additional prehospital doses for adequate sedation. There were no adverse events recorded in the patients administered haloperidol. In the midazolam group, the mean time to achieve a RASS score of less than +1 was 13.5 minutes (95% CI, 8-19 minutes) and the mean time for the return of normal mental status was 105 minutes (95% CI, 0-178 minutes). One patient required additional sedation in the ED. There were no adverse events recorded among the patients administered midazolam. Midazolam and haloperidol administered intramuscularly appear equally effective for sedating an agitated patient in the

Facile stripping voltammetric determination of haloperidol using a high performance magnetite/carbon nanotube paste electrode in pharmaceutical and biological samples

International Nuclear Information System (INIS)

Bagheri, Hasan; Afkhami, Abbas; Panahi, Yunes; Khoshsafar, Hosein; Shirzadmehr, Ali

2014-01-01

Multi-walled carbon nanotubes decorated with Fe 3 O 4 nanoparticles were prepared to construct a novel sensor for the determination of haloperidol (Hp) by voltammetric methods. The morphology and properties of electrode surface were characterized by scanning electron microscopy (SEM) and electrochemical impedance spectroscopy. This modified sensor was used as a selective electrochemical sensor for the determination of trace amounts of Hp. The peak currents of differential pulse and square wave voltammograms of Hp increased linearly with its concentration in the ranges of 1.2 × 10 −3 –0.52 and 6.5 × 10 −4 –0.52 μmol L −1 , respectively. The detection limits for Hp were 7.02 × 10 −4 and 1.33 × 10 −4 μmol L −1 for differential pulse and square wave voltammetric methods, respectively. The results show that the combination of multi-walled carbon nanotubes and Fe 3 O 4 nanoparticles causes a dramatic enhancement in the sensitivity of Hp quantification. This sensor was successfully applied to determine Hp in pharmaceutical samples and biological fluids. The fabricated electrode showed excellent reproducibility, repeatability and stability. - Highlights: • A sensitive paste using Fe 3 O 4 /multi-walled carbon nanotubes was fabricated. • Haloperidol determination is based on its adsorption on the surface of Fe 3 O 4 /MWCNTs. • Different electrochemical methods and impedance spectroscopy were used for this study. • Haloperidol was determined in pharmaceutical and biological samples. • In comparison to other conventional methods, this method is simple, rapid, selective and cost-effective

Pubertal development in children diagnosed with diabetes mellitus type 1 before puberty.

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Pereira, K C X; Pugliese, B S; Guimarães, M M; Gama, M P

2015-02-01

To investigate an association between pubertal development and timing of menarche with glycemic control, disease duration, and body mass index (BMI) in patients diagnosed with diabetes mellitus type 1 (DM1) before puberty. Retrospective study. The study was performed at the diabetes outpatient clinic of Instituto de Puericultura e Pediatria Martagão Gesteira--IPPMG of the Federal University of Rio de Janeiro--UFRJ. A total of 131 children, 61 girls and 70 boys, diagnosed with DM1 before puberty participated in the study. The study investigated how age at puberty onset relates to mean glycated hemoglobin (HbA1c) before puberty, BMI percentile, and disease duration; how puberty duration relates to mean HbA1c before and during puberty and to disease duration; and how timing of menarche relates to mean HbA1c before puberty, BMI percentile, and disease duration. Age at puberty onset was positively correlated with mean HbA1c before puberty (r = 0.204, R(2) = 0.042; P = .019) and disease duration (r = 0.451, R(2) = 0.203; P puberty later than those diagnosed more recently. Girls in higher BMI percentiles reached menarche sooner.

Aplicación de la Metodología QTC en el Diseño de una Máquina Desespinadora de Nopal

OpenAIRE

Alvarez Ramírez, Jaime T.

1998-01-01

En la presente tesis se propone un Modelo del Proceso de Diseño de Nuevos Productos Manufacturados sustentado en la Metodología QTC (QFDTRIZ-CAD), la cual integra las herramientas Despliegue de la Función de Calidad (QFD, por sus siglas en inglés), Teoría de la Solución de Problemas de Inventiva (TRIZ) y Diseño Asistido por Computadora (CAD). Se presenta una descripción de éstas y otras herramientas auxiliares de diseño involucradas en el modelo. Se exponen los resultados derivados de la apli...

Facile stripping voltammetric determination of haloperidol using a high performance magnetite/carbon nanotube paste electrode in pharmaceutical and biological samples

Energy Technology Data Exchange (ETDEWEB)

Bagheri, Hasan, E-mail: h.bagheri@srbiau.ac.ir [Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences, Tehran (Iran, Islamic Republic of); Afkhami, Abbas [Faculty of Chemistry, Bu-Ali Sina University, Hamedan (Iran, Islamic Republic of); Panahi, Yunes [Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences, Tehran (Iran, Islamic Republic of); Khoshsafar, Hosein; Shirzadmehr, Ali [Faculty of Chemistry, Bu-Ali Sina University, Hamedan (Iran, Islamic Republic of)

2014-04-01

Multi-walled carbon nanotubes decorated with Fe{sub 3}O{sub 4} nanoparticles were prepared to construct a novel sensor for the determination of haloperidol (Hp) by voltammetric methods. The morphology and properties of electrode surface were characterized by scanning electron microscopy (SEM) and electrochemical impedance spectroscopy. This modified sensor was used as a selective electrochemical sensor for the determination of trace amounts of Hp. The peak currents of differential pulse and square wave voltammograms of Hp increased linearly with its concentration in the ranges of 1.2 × 10{sup −3}–0.52 and 6.5 × 10{sup −4}–0.52 μmol L{sup −1}, respectively. The detection limits for Hp were 7.02 × 10{sup −4} and 1.33 × 10{sup −4} μmol L{sup −1} for differential pulse and square wave voltammetric methods, respectively. The results show that the combination of multi-walled carbon nanotubes and Fe{sub 3}O{sub 4} nanoparticles causes a dramatic enhancement in the sensitivity of Hp quantification. This sensor was successfully applied to determine Hp in pharmaceutical samples and biological fluids. The fabricated electrode showed excellent reproducibility, repeatability and stability. - Highlights: • A sensitive paste using Fe{sub 3}O{sub 4}/multi-walled carbon nanotubes was fabricated. • Haloperidol determination is based on its adsorption on the surface of Fe{sub 3}O{sub 4}/MWCNTs. • Different electrochemical methods and impedance spectroscopy were used for this study. • Haloperidol was determined in pharmaceutical and biological samples. • In comparison to other conventional methods, this method is simple, rapid, selective and cost-effective.

Comparison of QT dispersion between subclinical hypothyroid and euthyroid patients

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Muharrem Kıskaç

2010-06-01

Full Text Available Objectives: The aim of this study was to investigate the relationship between subclinical hypothyroid and QTc dispersionindicating local heterogeneity in repolarization of myocardium, which is well known as independent cardiac risk factor for sudden death and ventricular arrhythmia.Materials and Methods: We compared QTc dispersion of subclinical hypothyroid patients, after treatment and healthy control group. We included a total of 50 patients with 41 women and 9 men in the study group. Electrocardiographywith 12 derivations, thyroid hormones, serum electrolytes and basic biochemical parameters were measured.The control group consisted of 25 healthy individuals.QT distances were calculated by using Bazet formula. The difference between the longest QTc and the shortest QTc distance was accepted as QTc dispersion (QTcd.Results: Comparison of subclinical hypothyroid patients, their euthyroidic period after treatment and healthy controlgroup, gave no significant differences in age, body weight, body mass index and free thyroxin values. However,significant difference was found in durations of QTd and QTcd between the subclinical hypothyroid, the control and the euthyroidic groups (p0.05.Conclusion: Our results suggested that subclinical hypothyroidpatients had longer QTc dispersion compared to euthyroidic period and healthy subjects. However there was no QTcd difference between the euthyroidic period and healthy control group.

Electrocardiography and serum potassium before and after hemodialysis sessions

International Nuclear Information System (INIS)

Tarif, N.; Al-Wakeel, Jamal Saleh; Sulaimani, F.; Memon, Nawaz Ali; Al-Suwaida, Abdul Kareem; Yamani, H.; Bakhsh, Ahmed Jahangir

2008-01-01

This study was undertaken to assess potassium level and electrocardiographic (ECG) changes post hemodialysis and whether fall in potassium level during hemodialysis may potentiate cardiac arrythemia. We studied 21 chronic hemodialysis (HD) patients who had their serum electrolytes measured before and after dialysis session and ECG performed at the same time. The patients included 14 females and 7 males with a mean age of 53.1+-15.6 years and range from 26 to 81 years; 9 (43%) patients were diabetics. All the patients had been on dialysis for a minimum of 6 months each Pre-HD serum potassium levels had no correlation with any ECG parameters except a negative correlation with T wave amplitude r=-0.5, p=0.021. ECG parameters significantly changed post-HD; the T wave amplitude decreased and the R wave amplitude increased. A comparatively higher R wave significantly decreased the T to R wave ratio post dialysis. The QRS duration and QTc interval also increased significantly. The patients with post-HD serum potassium of 3.5 mmol/L had a higher R wave amplitude and a significantly less T to R wave ratio (11.8+-9.7 vs 6.4+-5.1, p=0.045 and 0.4+-0.38 vs 1.0+-0.97, p=0.049, respectively. In patients with serum potassium decrement of >2.0 mmol/L, the T to R wave ratio decreased significantly, 0.32+-0.21 vs 0.85+-0.26, p=0.023; The T wave amplitude decreased more than the rise in R wave. Multiple regression analysis did not reveal any relationship of pre or post HD ECG changes and serum potassium, serum calcium or net change in serum potassium post-HD. We conclude that post-HD serum potassium decrement results in a decrease in T to R wave ratio on ECG; this change may have an arrhythmogenic potential. (author)

Characterization and bioactivity of novel calcium antagonists - N-methoxy-benzyl haloperidol quaternary ammonium salt

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Chen, Yi-Cun; Zhu, Wei; Zhong, Shu-Ping; Zheng, Fu-Chun; Gao, Fen-Fei; Zhang, Yan-Mei; Xu, Han; Zheng, Yan-Shan; Shi, Gang-Gang

2015-01-01

BACKGROUND AND PURPOSE Calcium antagonists play an important role in clinical practice. However, most of them have serious side effects. We have synthesized a series of novel calcium antagonists, quaternary ammonium salt derivatives of haloperidol with N-p-methoxybenzyl (X1), N-m-methoxybenzyl (X2) and N-o-methoxybenzyl (X3) groups. The objective of this study was to investigate the bioactivity of these novel calcium antagonists, especially the vasodilation activity and cardiac side-effects. The possible working mechanisms of these haloperidol derivatives were also explored. EXPERIMENTAL APPROACH Novel calcium antagonists were synthesized by amination. Compounds were screened for their activity of vasodilation on isolated thoracic aortic ring of rats. Their cardiac side effects were explored. The patch-clamp, confocal laser microscopy and the computer-fitting molecular docking experiments were employed to investigate the possible working mechanisms of these calcium antagonists. RESULTS The novel calcium antagonists, X1, X2 and X3 showed stronger vasodilation effect and less cardiac side effect than that of classical calcium antagonists. They blocked L-type calcium channels with an potent effect order of X1 > X2 > X3. Consistently, X1, X2 and X3 interacted with different regions of Ca2+-CaM-CaV1.2 with an affinity order of X1 > X2 > X3. CONCLUSIONS The new halopedidol derivatives X1, X2 and X3 are novel calcium antagonists with stronger vasodilation effect and less cardiac side effect. They could have wide clinical application. PMID:26544729

Low doses of haloperidol combined with ondansetron are not effective for prophylaxis of postoperative nausea and vomiting in susceptible patients.

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Veiga-Gil, Leonor; López-Olaondo, Luis; Pueyo, Javier; Callejas, Raquel; Duque, Paula; Carrascosa, Francisco

2015-02-01

In this observational study we reviewed the efficacy and side effects of different antiemetic combinations used in our hospital for postoperative nausea and vomiting (PONV) prophylaxis in high-risk women undergoing highly emetogenic surgery. After reviewing retrospectively the medical records of patients undergoing highly emetogenic elective surgeries under general anaesthesia, we selected 368 women whose Apfel risk score was ≥ 3 and receiving a combination of 2 antiemetics for PONV prophylaxis. We analysed the incidence of PONV at 2, 6, 12 and 24h after surgery, antiemetic rescue requirements, pattern of occurrence of PONV, side effects and level of sedation were also assessed. The main goal was complete response defined as no PONV within 24h after surgery. Ondansetron 4mg i.v. plus dexamethasone 8mg i.v. (O&Dex), haloperidol 1mg i.v. (O&Hal1), haloperidol 2mg i.v. (O&Hal2) or droperidol 1.25mg i.v. (O&Dro) were the combinations most frequently used. The complete response was better in groups O&Dex: 68.5% (CI: 58-78), O&Hal2: 64.1% (CI: 53-74) and O&Dro 63% (CI: 52-73) than in group O&Hal1: 41.3% (CI: 31-52) (p<0,01). Peak incidence of PONV occurred within the 2-6h period. The incidence of side effects was higher in group O&Hal2. In high risk patients for PONV who underwent highly emetogenic surgeries, the efficacy of low-dose haloperidol (1mg) in combination is limited. Higher doses (2mg) are more effective but its use is associated with a high incidence of side effects. Copyright © 2013 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

[Healthier after Psychotherapy? Analysis of Claims Data (Lower Saxony, Germany) on Sickness Absence Duration before and after Outpatient Psychotherapy].

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Epping, Jelena; de Zwaan, Martina; Geyer, Siegfried

2017-11-17

Introduction In employed populations sickness absence can be used as a good indicator of health status. In the present study, it was examined how periods of sickness absence are developing within one year before and after psychotherapy under comparison of three types of psychotherapy (behavior therapy, psychodynamic psychotherapy, and psychoanalysis), all fully covered by statutory health insurance. Methods and data The analyses were performed with pseudonymized claims data from the AOK Niedersachsen, a statutory health insurance (N=2,900,065 insured). Certified sickness absences before and after psychotherapy were examined for 9,916 patients. Parallelized controls were used to build a comparison of the length of sickness absences. Analyses were performed separately for women and for men. Results Within one year before starting psychotherapy, patients had longer sickness absences than controls on average. There was a reduction in the length of sickness absence of 20 days (median) within one year before to 12 days (median) within one year after the psychotherapy. The obtained differences between types of psychotherapy were considerable. Discussion Differences in terms of sickness absences may in part be explained by socio-demographic differences. Patients who underwent psychoanalysis were younger and had higher educational levels. However, it remains unclear why the differences of sickness absence periods were that high. It has to be discussed whether self-selection of patients with better health into psychoanalysis had occurred. Conclusions Patients undergoing psychoanalysis differ from patients who underwent other types of psychotherapy in terms of their duration of sickness absence as well as socio-demographic profile. Thus, due to differences in the composition of patients future research in psychotherapy will have to differentiate by type of psychotherapy. © Georg Thieme Verlag KG Stuttgart · New York.

Differential Long-Term Effects of Haloperidol and Risperidone on the Acquisition and Performance of Tasks of Spatial Working and Short-Term Memory and Sustained Attention in Rats

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Hutchings, Elizabeth J.; Waller, Jennifer L.

2013-01-01

A common feature of the neuropsychiatric disorders for which antipsychotic drugs are prescribed is cognitive dysfunction, yet the effects of long-term antipsychotic treatment on cognition are largely unknown. In the current study, we evaluated the effects of long-term oral treatment with the first-generation antipsychotic haloperidol (1.0 and 2.0 mg/kg daily) and the second-generation antipsychotic risperidone (1.25 and 2.5 mg/kg daily) on the acquisition and performance of two radial-arm maze (RAM) tasks and a five-choice serial reaction-time task (5C-SRTT) in rats during days 15–60 and 84–320 days of treatment, respectively. In the RAM, neither antipsychotic significantly affected the acquisition or performance of a spatial win shift or a delayed non–match-to-position task. Conversely, in the rats administered 5C-SRTT, haloperidol was associated with profound deficits in performance, and the subjects were not able to progress through all stages of task acquisition. Depending on the dose, risperidone was associated with a greater number of trials to meet specific performance criteria during task acquisition compared with vehicle-treated controls; however, most subjects were eventually able to achieve all levels of task acquisition. Both haloperidol and risperidone also increased the number of perseverative and time-out responses during certain stages of task acquisition, and the response and reward latencies were slightly higher than controls during several stages of the study. These results in rats suggest that while long-term treatment with haloperidol or risperidone may not significantly affect spatial working or short-term memory, both antipsychotics can (depending on dose) impair sustained attention, decrease psychomotor speed, increase compulsive-type behaviors, and impair cognitive flexibility. PMID:24042161

Differential long-term effects of haloperidol and risperidone on the acquisition and performance of tasks of spatial working and short-term memory and sustained attention in rats.

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Hutchings, Elizabeth J; Waller, Jennifer L; Terry, Alvin V

2013-12-01

A common feature of the neuropsychiatric disorders for which antipsychotic drugs are prescribed is cognitive dysfunction, yet the effects of long-term antipsychotic treatment on cognition are largely unknown. In the current study, we evaluated the effects of long-term oral treatment with the first-generation antipsychotic haloperidol (1.0 and 2.0 mg/kg daily) and the second-generation antipsychotic risperidone (1.25 and 2.5 mg/kg daily) on the acquisition and performance of two radial-arm maze (RAM) tasks and a five-choice serial reaction-time task (5C-SRTT) in rats during days 15-60 and 84-320 days of treatment, respectively. In the RAM, neither antipsychotic significantly affected the acquisition or performance of a spatial win shift or a delayed non-match-to-position task. Conversely, in the rats administered 5C-SRTT, haloperidol was associated with profound deficits in performance, and the subjects were not able to progress through all stages of task acquisition. Depending on the dose, risperidone was associated with a greater number of trials to meet specific performance criteria during task acquisition compared with vehicle-treated controls; however, most subjects were eventually able to achieve all levels of task acquisition. Both haloperidol and risperidone also increased the number of perseverative and time-out responses during certain stages of task acquisition, and the response and reward latencies were slightly higher than controls during several stages of the study. These results in rats suggest that while long-term treatment with haloperidol or risperidone may not significantly affect spatial working or short-term memory, both antipsychotics can (depending on dose) impair sustained attention, decrease psychomotor speed, increase compulsive-type behaviors, and impair cognitive flexibility.

Comparison of the Effects of Haloperidol and Benzodiazepines Used for Postictal Psychiatric Symptoms on Seizure Recurrence: A Pilot Study

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Pınar Hanife Kara

2017-09-01

Full Text Available Aim: Patients with epilepsy may experience a number of psychiatric and cognitive symptoms or behavioral manifestations during the period of a seizure and the postictal period. The aim of this pilot study was to compare the effects medications commonly used in emergency departments for postictal psychiatric symptoms on seizure recurrence. Methods: Data of 32 epileptic patients, who presented to İzmir Katip Çelebi University Atatürk Research and Training Hospital Emergency Department with postictal psychiatric symptoms between January 2013 and December 2014, were retrospectively collected. Demographic and clinical data were obtained from the emergency department charts and neurology and psychiatry consultation records. Data regarding administered drugs were obtained from the hospital data processing system. The chi-square test, Mann-Whitney U test and the Kruskal-Wallis test were used as statistical methods. Bonferroni correction was performed for post-hoc analysis. Results: There were no differences in the seizure recurrence rate between benzodiazepine, haloperidol and without medication groups (p>0.05. Conclusion: Our results suggest that benzodiazepines and haloperidol do not affect the development of recurrent seizures when administered for postictal symptoms.

Expression changes of serotonin receptor gene subtype 5HT3a in peripheral blood mononuclear cells from schizophrenic patients treated with haloperidol and Olanzapin.

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Shariati, Gholam Reza; Ahangari, Ghasem; Hossein-nezhad, Arash; Asadi, Seyed Mohammad; Pooyafard, Farzaneh; Ahmadkhaniha, Hamid Reza

2009-09-01

Serotonin receptors are involved in pathophysiology of schizophrenia and may mediate other neurotransmitter effects. We investigated serotonin receptors gene expression in peripheral blood mononuclear cells (PBMC) of naïve schizophrenic patients, before and after treatment. Also serotonin receptor gene expression was compared in two treatment groups including Haloperidol and Olanzapine. The PBMC was separated from whole blood by Ficoll-hypaque. The total cellular RNA was extracted and the cDNA was synthesized. This process was followed by real-time PCR using primer pairs specific for 5HT(3a) serotonin receptor mRNA and beta-actin as internal control. The results showed the presence of subtype of serotonin receptor in lymphocytes. Serotonin gene expression showed significant changes in Olanzapine treatment group which correlated with Clinical Global Impression (CGI) score improvement. In conclusion, the present study has shown that human PBMC express serotonin receptors 5HT(3a). Moreover, clinical symptom improvement of Olanzapin may be demonstrated by a change in serotonin receptor gene expression.

Atrial and Ventricular Electrocardiographic Dromotropic Disturbances in Down Syndrome Patients with Structurally Normal Heart: A Cross-Sectional Study

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Yazdan Ghandi

2018-03-01

Full Text Available Background: We designed a cross-sectional study to determine electrocardiographic disorders in Down syndrome patients with congenitally normal hearts in a bid to predict fatal cardiac arrhythmia in the future. Materials and Methods: We investigated 60 children with DS without congenital abnormal hearts. Sixty healthy juveniles were also included in the study as a control group. Physical examination, electrocardiography, and echocardiography were performed in all subjects. Corrected QT interval (QTc was measured according to Bazett’s formula. Results: Patients with DS consisted of 32 males (53.33%, and 28 females (46.66%, aged 6–13 (9.21 ± 6.24 years old. Healthy subjects comprised 31 males (51.66%, and 29 females (48.33% with a mean age of 9.15 ± 5.01. The two groups were significantly different in terms of heart rate (P=0.006, maximum P-wave duration (P=0.001, and P-wave dispersion (PWd, P=0.0001. There was no statistically significant difference regarding minimum P-wave duration (P=0.176. The patients with DS had a greater maximum QTc interval, QT dispersion, and corrected QT interval dispersion (QTc-d than the healthy control subjects (P=0.001. However, there was no difference in maximum QT interval and minimum QTc interval between the two groups (P=0.67 and P=0.553, respectively. A positive correlation was found between age, heart rate, and all electrocardiographic variables. Conclusion: All DS patients, even in the absence of concomitant congenital heart disease should be followed up carefully by electrocardiography, looking for increased PWd and QTc-d to detect predisposed cases to arrhythmia.

Carrier-added and no-carrier-added syntheses of (/sup 18/F)spiroperidol and (/sub 18/F)haloperidol

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Kilbourn, M R; Welch, M J; Dence, C S; Tewson, T J; Saji, H; Maeda, M

1984-07-01

Syntheses of (18F)haloperidol and (18F)spiroperidol in both no-carrier-added and carrier-added forms have been accomplished. The no-carrier-added (18F)butyrophenone neuroleptics were prepared in low (less than 2%) yield by acid decomposition of aryl piperidine triazenes. Carrier-added 18F-neuroleptics were prepared in better (5-17%) yields by 18F-for-19F nucleophilic aromatic substitution. The preparation of all synthetic precursors, and procedures for radiolabeling are fully described.

Potent haloperidol derivatives covalently binding to the dopamine D2 receptor.

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Schwalbe, Tobias; Kaindl, Jonas; Hübner, Harald; Gmeiner, Peter

2017-10-01

The dopamine D 2 receptor (D 2 R) is a common drug target for the treatment of a variety of neurological disorders including schizophrenia. Structure based design of subtype selective D 2 R antagonists requires high resolution crystal structures of the receptor and pharmacological tools promoting a better understanding of the protein-ligand interactions. Recently, we reported the development of a chemically activated dopamine derivative (FAUC150) designed to covalently bind the L94C mutant of the dopamine D 2 receptor. Using FAUC150 as a template, we elaborated the design and synthesis of irreversible analogs of the potent antipsychotic drug haloperidol forming covalent D 2 R-ligand complexes. The disulfide- and Michael acceptor-functionalized compounds showed significant receptor affinity and an irreversible binding profile in radioligand depletion experiments. Copyright © 2017 Elsevier Ltd. All rights reserved.

Are all first-generation antipsychotics equally effective in treating schizophrenia? A meta-analysis of randomised, haloperidol-controlled trials.

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Dold, Markus; Tardy, Magdolna; Samara, Myrto T; Li, Chunbo; Kasper, Siegfried; Leucht, Stefan

2016-04-01

Narrative, unsystematic reviews revealed no differences in efficacy between the various first-generation antipsychotics (FGAs) resulting in the psychopharmacological assumption of comparable efficacy between the different FGAs. We sought to determine if the assumption of comparable efficacy of all FGAs can be regarded as evidence-based using meta-analytic statistics. A systematic literature survey (Cochrane Schizophrenia Group trial register) was applied to identify all RCTs that compared oral haloperidol with another oral FGA in schizophrenia. Primary outcome was dichotomous treatment response. Secondary outcomes were symptom severity measured by rating scales, discontinuation rates, and specific adverse effects. Altogether, 79 RCTs with 4343 participants published between 1962 and 1999 were included. We found a significant between-group difference only between haloperidol and nemonapride, but not for the remaining 19 investigated FGAs. There were no significant differences for discontinuation rates. As most of the single meta-analytic comparisons can be regarded as underpowered, the evidence for the assumption of comparable efficacy of all FGAs is inconclusive. We therefore cannot confirm or reject the statements of previous narrative, unsystematic reviews in this regard. Our findings were limited by the small sample size in the individual comparisons and the low methodological quality in many included studies.

Haloperidol plus dexamethasone versus dexamethasone alone to prevent postoperative nausea and vomiting in patients undergoing ambulatory surgery: a randomized, controlled and double-blind study

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Nelson Javier González

2008-02-01

Full Text Available

BACKGROUND AND GOAL OF THE STUDY: haloperidol is an effective antiemetic drug. We sought to determine whether haloperidol and dexamethasone prophylaxis schemes decrease the incidence of postoperative nausea and vomiting (PONV in patients undergoing ambulatory surgery.

MATERIALS AND METHODS: we enrolled 160 non-smoking females who received a standardized anesthesia technique including 8 mg of dexamethasone at the beginning of surgery. They were then randomized to receive either 1.5 mg of haloperidol (DH group or placebo (DP group 30 minutes before the end of surgery. The incidence of PONV was assessed by a blinded investigator at 30 minutes and at 2, 6 and 24 hours in the postoperative period. Analgesic requirements, ocular opening time and sedation were also assessed. The quantitative variables of normal distribution were evaluated with the t-student test and the ones with abnormal distribution, with the U-Mann Whitney test. Qualitative variables were evaluated with the Fisher test.

RESULTS AND DISCUSSION: both groups were homogeneous in demographic characteristics (30.1 vs. 29.5 years, 55.9 vs. 56 kg and history of PONV in 21.5% vs. 21.2% in DH group vs. DP group, respectively. At 6 hours postoperatively we found no difference in the incidence of nausea (22.5% vs. 27.5%; RR: 0.81, CI 95%: 0.56 -1

Carrier-added and no-carrier-added syntheses of (/sup 18/F)spiroperidol and (/sup 18/F)haloperidol

Energy Technology Data Exchange (ETDEWEB)

Kilbourn, M R; Welch, M J; Dence, C S; Tewson, T J; Saji, H; Maeda, M [Washington Univ., St. Louis, MO (USA). Edward Mallinckrodt Inst. of Radiology

1984-07-01

Syntheses of (/sup 18/F)haloperidol and (/sup 18/F)spiroperidol in both no-carrier-added and carrier-added forms have been accomplished. The no-carrier-added (/sup 18/F)butyrophenone neuroleptics were prepared in low (<2%) yield by acid decomposition of aryl piperidine triazenes. Carrier-added /sup 18/F-neuroleptics were prepared in better (5-17%) yields by /sup 18/F-for-/sup 19/F nucleophilic aromatic substitution. The preparation of all synthetic precursors, and procedures for radiolabeling are fully described.

sigma opiates and certain antipsychotic drugs mutually inhibit (+)-[3H]SKF 10,047 and [3H]haloperidol binding in guinea pig brain membranes

International Nuclear Information System (INIS)

Tam, S.W.; Cook, L.

1984-01-01

The relationship between binding of antipsychotic drugs and sigma psychotomimetic opiates to binding sites for the sigma agonist (+)-[ 3 H]SKF 10,047 (N-allylnormetazocine) and to dopamine D 2 sites was investigated. In guinea pig brain membranes, (+)-[ 3 H]SKF 10,047 bound to single class of sites with a K/sub d/ of 4 x 10 -8 M and a B/sub max/ of 333 fmol/mg of protein. This binding was different from μ, kappa, or delta opiate receptor binding. It was inhibited by opiates that produce psychotomimetic activities but not by opiates that lack such activities. Some antipsychotic drugs inhibited (+)-[ 3 H]SKF 10,047 binding with high to moderate affinities in the following order of potency: haloperidol > perphenazine > fluphenazine > acetophenazine > trifluoperazine > molindone greater than or equal to pimozide greater than or equal to thioridazine greater than or equal to chlorpromazine greater than or equal to triflupromazine. However, there were other antipsychotic drugs such as spiperone and clozapine that showed low affinity for the (+)-[ 3 H]SKF 10,047 binding sites. Affinities of antipsychotic drugs for (+)-[ 3 H]SKF 10,047 binding sites did not correlate with those for [ 3 H]spiperone (dopamine D 2 ) sites. [ 3 H]-Haloperidol binding in whole brain membranes was also inhibited by the sigma opiates pentazocine, cyclazocine, and (+)-[ 3 H]SKF 10,047. In the striatum, about half of the saturable [ 3 H]haloperidol binding was to [ 3 H]spiperone (D 2 ) sites and the other half was to sites similar to (+)-[ 3 H]SKF 10,047 binding sites. 15 references, 4 figures, 1 table

[3H]Haloperidol labels brain dopamine receptors after its injection into the internal carotid artery of the rat

International Nuclear Information System (INIS)

D'Ambrosio, A.; Zivkovic, B.; Bartholini, G.

1982-01-01

Pulse injection of [ 3 H]haloperidol (0.1 μCi; 0.003 μg) into the internal carotid artery of the rat specifically labelled dopamine receptors in striatum and olfactory tubercle, as indicated by the kinetics of, and the effects of neuroleptic drugs on, the ligand disposition. The described method may prove useful for labelling brain receptors with ligands which readily cross the blood-brain barrier but which do not selectively mark their receptors if injected systemically. (Auth.)

Ventricular Effective Refraction Period and Ventricular Repolarization Analysis in Experimental Tachycardiomyopathy in Swine.

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Noszczyk-Nowak, Agnieszka; Pasławska, Urszula; Gajek, Jacek; Janiszewski, Adrian; Pasławski, Robert; Zyśko, Dorota; Nicpoń, Józef

2016-01-01

Swine are recognized animal models of human cardiovascular diseases. However, little is known on the CHF-associated changes in the electrophysiological ventricular parameters of humans and animals. The aim of this study was to analyze changes in the durations of ventricular effective refraction period (VERP), QT and QTc intervals of pigs with chronic tachycardia-induced tachycardiomyopathy (TIC). The study was comprised of 28 adult pigs (8 females and 20 males) of the Polish Large White breed. A one-chamber pacemaker was implanted in each of the 28 pigs. Electrocardiographic, echocardiographic and electrophysiological studies were carried out prior to the pacemaker implantation and at subsequent 4-week intervals. All electrocardiographic, echocardiographic and short electrophysiological study measurements in all swine were done under general anesthesia (propofol) after premedication with midazolam, medetomidine, and ketamine. No significant changes in the duration of QT interval and corrected QT interval (QTc) were observed during consecutive weeks of the experiment. The duration of the QTc interval of female pigs was shown to be significantly longer than that of the males throughout the whole study period. Beginning from the 12th week of rapid ventricular pacing, a significant increase in duration of VERP was observed in both male and female pigs. Males and females did not differ significantly in terms of VERP duration determined throughout the whole study period. Ventricular pacing, stimulation with 2 and 3 premature impulses at progressively shorter coupling intervals and an imposed rhythm of 130 bpm or 150 bpm induced transient ventricular tachycardia in one female pig and four male pigs. One episode of permanent ventricular tachycardia was observed. The number of induced arrhythmias increased proportionally to the severity of heart failure and duration of the experiment. However, relatively aggressive protocols of stimulation were required in order to induce

QT interval and dispersion in drug-free anorexia nervosa adolescents: a case control study.

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Bomba, Monica; Tremolizzo, Lucio; Corbetta, Fabiola; Nicosia, Franco; Lanfranconi, Francesca; Poggioli, Gianni; Goulene, Karine; Stramba-Badiale, Marco; Conti, Elisa; Neri, Francesca; Nacinovich, Renata

2017-11-16

Long QT values have been reported in patients with anorexia nervosa of the restricting type (ANr) potentially increasing the risk of fatal arrhythmia, especially if psychotropic drug treatment is required. Nevertheless, the previous studies on this topic are biased by drug exposure, long disease durations, and small sample sizes. This study is aimed at assessing QTc and QTcd values in ANr adolescents with recent onset and drug free, as compared to subjects affected by psychiatric disorders other than ANr. We evaluated QTc and its dispersion (QTcd) in a population of 77 drug-free ANr female adolescents and compared to an equal number of healthy controls (H-CTRL) and pathological controls (P-CTRL, mixed psychiatric disorders). The QT determination was performed on a standard simultaneous 12-lead ECG in blind by a single experienced investigator. QTc was calculated by the Bazett's formula and QTcd was determined as the difference between the maximum and minimum QTc intervals in different leads. Only for ANr patients, clinico-demographic data, hormones, and electrolytes were obtained. QTc was slightly reduced in ANr patients (27.7 ms, studies are needed to understand if the previously reported increase might be related to other associated chronic disorders, such as hormonal or electrolyte imbalance.

Effect of alectinib on cardiac electrophysiology: results from intensive electrocardiogram monitoring from the pivotal phase II NP28761 and NP28673 studies.

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Morcos, Peter N; Bogman, Katrijn; Hubeaux, Stanislas; Sturm-Pellanda, Carolina; Ruf, Thorsten; Bordogna, Walter; Golding, Sophie; Zeaiter, Ali; Abt, Markus; Balas, Bogdana

2017-03-01

Alectinib, a central nervous system (CNS)-active ALK inhibitor, has demonstrated efficacy and safety in ALK+ non-small-cell lung cancer that has progressed following crizotinib treatment. Other ALK inhibitors have shown concentration-dependent QTc prolongation and treatment-related bradycardia. Therefore, this analysis evaluated alectinib safety in terms of electrophysiologic parameters. Intensive triplicate centrally read electrocardiogram (ECG) and matched pharmacokinetic data were collected across two alectinib single-arm trials. Analysis of QTcF included central tendency analysis [mean changes from baseline with one-sided upper 95% confidence intervals (CIs)], categorical analyses, and relationship between change in QTcF and alectinib plasma concentrations. Alectinib effects on other ECG parameters (heart rate, PR interval and QRS duration) were also evaluated. Alectinib did not cause a clinically relevant change in QTcF. The maximum mean QTcF change from baseline was 5.3 ms observed pre-dose at week 2. The upper one-sided 95% CI was exposure-dependent decrease in mean heart rate of ~11 to 13 beats per minute at week 2. No clinically relevant effects were seen on other ECG parameters. Approximately 5% of patients reported cardiac adverse events of bradycardia or sinus bradycardia; however, these were all grade 1-2. Alectinib does not prolong the QTc interval or cause changes in cardiac function to a clinically relevant extent, with the exception of a decrease in heart rate which was generally asymptomatic.

Long-Duration Space Flight and Bed Rest Effects on Testosterone and Other Steroids

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Heer, Martina; Wang, Zuwei; Huntoon, Carolyn L.; Zwart, Sara R.

2012-01-01

Context: Limited data suggest that testosterone is decreased during space flight, which could contribute to bone and muscle loss. Objective: The main objective was to assess testosterone and hormone status in long- and short-duration space flight and bed rest environments and to determine relationships with other physiological systems, including bone and muscle. Design: Blood and urine samples were collected before, during, and after long-duration space flight. Samples were also collected before and after 12- to 14-d missions and from participants in 30- to 90-d bed rest studies. Setting: Space flight studies were conducted on the International Space Station and before and after Space Shuttle missions. Bed rest studies were conducted in a clinical research center setting. Data from Skylab missions are also presented. Participants: All of the participants were male, and they included 15 long-duration and nine short-duration mission crew members and 30 bed rest subjects. Main Outcome Measures: Serum total, free, and bioavailable testosterone were measured along with serum and urinary cortisol, serum dehydroepiandrosterone, dehydroepiandrosterone sulfate, and SHBG. Results: Total, free, and bioavailable testosterone was not changed during long-duration space flight but were decreased (P space flight. There were no changes in other hormones measured. Testosterone concentrations dropped before and soon after bed rest, but bed rest itself had no effect on testosterone. Conclusions: There was no evidence for decrements in testosterone during long-duration space flight or bed rest. PMID:22049169

Verifying the competition between haloperidol and biperiden in serum albumin through a model based on spectrofluorimetry

Science.gov (United States)

Muniz da Silva Fragoso, Viviane; Patrícia de Morais e Coura, Carla; Paulino, Erica Tex; Valdez, Ethel Celene Narvaez; Silva, Dilson; Cortez, Celia Martins

2017-11-01

The aim of this work was to apply mathematical-computational modeling to study the interactions of haloperidol (HLP) and biperiden (BPD) with human (HSA) and bovine (BSA) serum albumin in order to verify the competition of these drugs for binding sites in HSA, using intrinsic tryptophan fluorescence quenching data. The association constants estimated for HPD-HSA was 2.17(±0.05) × 107 M-1, BPD-HSA was 2.01(±0.03) × 108 M-1 at 37 °C. Results have shown that drugs do not compete for the same binding sites in albumin.

Plasma catecholamine metabolites in schizophrenics: evidence for the two-subtype concept.

Science.gov (United States)

Chang, W H; Chen, T Y; Lin, S K; Lung, F W; Lin, W L; Hu, W H; Yeh, E K

1990-03-01

Plasma homovanillic acid (pHVA) and plasma methoxyhydroxyphenyl glycol (pMHPG), as well as plasma haloperidol, were measured in 33 schizophrenic patients before and during 6 weeks of haloperidol treatment. Good responders had higher baseline pHVA values compared with poor responders (17.4 +/- 8.8 ng/ml, n = 22 versus 11.4 +/- 5.0 ng/ml, n = 11, p less than 0.05). A higher than 15 ng/ml pretreatment pHVA level was associated with a more consistent clinical response to the subsequent treatment. Differential pHVA changes during treatment were also found between good and poor responders. Within the good responder group, a significant decline in pHVA over time was found. By contrast, pHVA showed a transient increase in the poor responder group. Plasma MHPG changes showed a similar pattern during treatment in good responders, although no significant differences in baseline values were found between the good (n = 13) and poor (n = 9) responders, and pMHPG showed no change during treatment in poor responders. Significant correlations between baseline pHVA and pMHPG values were found in 22 patients. Good responders and poor responders did not differ significantly in terms of age, duration of illness, severity of presenting symptoms, haloperidol dose, or plasma drug concentration. Two hypothetical subtypes of schizophrenia and both dopamine and norepinephrine systems involved in schizophrenic psychopathology are proposed.

(/sup 3/H)Haloperidol labels brain dopamine receptors after its injection into the internal carotid artery of the rat

Energy Technology Data Exchange (ETDEWEB)

D' Ambrosio, A; Zivkovic, B; Bartholini, G [Research Department, Synthelabo-L.E.R.S., Paris (France)

1982-04-29

Pulse injection of (/sup 3/H)haloperidol (0.1 ..mu..Ci; 0.003 ..mu..g) into the internal carotid artery of the rat specifically labelled dopamine receptors in striatum and olfactory tubercle, as indicated by the kinetics of, and the effects of neuroleptic drugs on, the ligand disposition. The described method may prove useful for labelling brain receptors with ligands which readily cross the blood-brain barrier but which do not selectively mark their receptors if injected systemically.

A comparative study of aripiprazole orally disintegrating tablets and Haloperidol treatment for tic disorders%阿立哌唑口腔崩解片与氟哌啶醇治疗抽动障碍的对比研究

Institute of Scientific and Technical Information of China (English)

郑庆梅; 李耀东; 邓良华; 谭助英

2015-01-01

Objective To evaluate the efficacy and tolerability of Aripiprazole orally disintegrating tablets and Haloperidol treatment in children with tic disorders. Method 61 Tourette patients were randomly divided into two groups,treatment with Aripiprazole orally disintegra-ting tablets and Haloperidol for 8 weeks. Before treatment and in the second,fourth and eighth weekend,YGTSSS and TESS were used to eval-uate efficacy and side effects. Results In the 2nd,4th and 8th weekend vocal tic,total damage and total scores of YGTSS both in Aripiprazole group and Haloperidol group significantly decreased. But in the second weekend motor tics score worse than haloperidol. In terms of safety,side effects and tolerance of Aripiprazole orally disintegrating tablets was better. Conclusion Aripiprazole orally disintegrating tabletsis effective for treatment of tic disorder,and high safety.%目的：比较阿立哌唑口腔崩解片和氟哌啶醇治疗抽动障碍的临床疗效和安全性。方法：将符合抽动障碍的61例儿童随机分为两组，分别接受氟哌啶醇和阿立哌唑口腔崩解片治疗，并在治疗2周、4周及8周末分别进行耶鲁综合抽动严重程度量表（Yale Global Tic Severity Scale，YGTSS）、不良反应量表（treatment emergent symptomscale，TESS）评估其疗效和安全性。结果：阿立哌唑口腔崩解片与氟哌啶醇组在治疗的2、4、8周末在YGTSS量表发声抽动、整体损害和YGTSS总分疗效评分上均无明显差异，在2周末运动抽动疗效评分上较氟哌啶醇差；在安全性方面，阿立哌唑口腔崩解片不良反应更小，耐受性更好。结论：阿立哌唑口腔崩解片在治疗抽动障碍上有显著的疗效，和更好地安全性。

Relationship Between Short Sleep Duration and Preseason Concussion Testing.

Science.gov (United States)

Silverberg, Noah D; Berkner, Paul D; Atkins, Joseph E; Zafonte, Ross; Iverson, Grant L

2016-05-01

Baseline, preseason assessment of cognition, symptoms, and balance has been recommended as part of a comprehensive sport concussion management program. We examined the relationship between sleep and baseline test results. We hypothesized that adolescents who slept fewer hours the night before would report more symptoms and perform more poorly on cognitive testing than students who had a full night sleep. Cross-sectional observation study. Preseason concussion testing for high school athletes. A large sample (n = 2928) of student athletes from Maine, USA, between the ages of 13 and 18 years completed preseason testing. Participants with developmental problems, a history of treatment for neurological or psychiatric problems, recent concussion, or 3 or more prior concussions were excluded. Athletes were divided into 4 groups based on their sleep duration the night before testing. Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT; ImPACT Applications, Inc, Pittsburgh, PA) cognitive composite scores and the embedded Post-Concussion Symptom Scale. Sleep was not related to any ImPACT cognitive composite score, after covarying for age and controlling for multiple comparisons. In contrast, there were sleep duration, sex, and sleep duration by sex effects on the Post-Concussion Symptom Scale. The effect of sleep duration on symptom reporting was more pronounced in girls. Supplementary analyses suggested that sleep insufficiency was associated with a diverse array of postconcussion-like symptoms. Poor sleep the night before baseline or postinjury testing may be an important confound when assessing postconcussion symptoms. Girls may be more vulnerable to experiencing and reporting symptoms following insufficient sleep. Clinicians should routinely ask how the athlete slept the night before preseason baseline testing and consider deferring the symptom assessment or later retesting athletes who slept poorly.

Successful control of intractable nausea and vomiting requiring combined ondansetron and haloperidol in a patient with advanced cancer.

Science.gov (United States)

Cole, R M; Robinson, F; Harvey, L; Trethowan, K; Murdoch, V

1994-01-01

Chemically induced nausea and vomiting is a common symptom of advanced cancer effected through stimulation of dopamine (D2) or serotonin (5-HT3) receptors located in the chemoreceptor trigger zone (CTZ). These may be blocked by therapeutic doses of haloperidol and ondansetron, respectively. This case, reporting on a single patient acting as her own control, establishes that combined blockade of these receptors is sometimes required to relieve intractable nausea and vomiting. It also demonstrates the value of clinical review, audit of care, and quality assurance in the palliative care setting.

Marked exacerbation of orthostatic intolerance after long- vs. short-duration spaceflight in veteran astronauts

Science.gov (United States)

Meck, J. V.; Reyes, C. J.; Perez, S. A.; Goldberger, A. L.; Ziegler, M. G.

2001-01-01

OBJECTIVE: The incidence of postflight orthostatic intolerance after short-duration spaceflight is about 20%. However, the incidence after long-duration spaceflight was unknown. The purpose of this study was to test the hypothesis that orthostatic intolerance is more severe after long-duration than after short-duration flight. METHODS: We performed tilt tests on six astronauts before and after long-duration (129-190 days) spaceflights and compared these data with data obtained during stand tests before and after previous short-duration missions. RESULTS: Five of the six astronauts studied became presyncopal during tilt testing after long-duration flights. Only one had become presyncopal during stand testing after short-duration flights. We also compared the long-duration flight tilt test data to tilt test data from 20 different astronauts who flew on the short-duration Shuttle missions that delivered and recovered the astronauts to and from the Mir Space Station. Five of these 20 astronauts became presyncopal on landing day. Heart rate responses to tilt were no different between astronauts on long-duration flights and astronauts on short-duration flights, but long-duration subjects had lower stroke volumes and cardiac outputs than short-duration presyncopal subjects, suggesting a possible decrease in cardiac contractile function. One subject had subnormal norepinephrine release with upright posture after the long flight but not after the short flight. Plasma volume losses were not greater after long flights. CONCLUSION: Long-duration spaceflight markedly increases orthostatic intolerance, probably with multiple contributing factors.

Effects of typical antipsychotic, haloperidol on regional cerebral blood flow in drug-naive schizophrenic patients-study with 99mTc-HMPAO SPECT

International Nuclear Information System (INIS)

Kamoya, Masatoshi

2001-01-01

For the purpose of examining antipsychotic action of haloperidol (HPD), effects of chronic perioral administration of HPD 4.5 mg/day on regional cerebral blood flow (rCBF) with 99mTc-HMPAO SPECT were investigated in 12 drug-naive schizophrenic patients with acute hallucinatory and delusional state. Further, the SPECT examinations were performed on 20 normal adult volunteers to investigate differences in rCBFs between schizophrenics and the normal subjects. Results are itemized as follows. The rCBF values were significantly increased in the bilateral superior and middle frontal, cingulate, middle temporal, pre-and post-central gyri, the left superior temporal gyrus, the bilateral inferior parietal lobule, and the bilateral hippocampal and thalamic cortices in comparison between normal subjects and before the HPD dose in schizophrenics. However, the rCBF values after the HPD dose showed significant increases only in the bilateral pre-and post-central gyri in comparison with the normal subjects. The rCBF values were significantly decreased in the bilateral superior, middle and inferior frontal, superior and middle temporal gyri, and the left insular gyrus after the HPD dose in comparison with before the HPD dose. The psychiatric assessment with PANSS showed an improvement of positive symptoms consisting of auditory hallucination and delusions after the HPD dose. Statistical analyses on relationships between the rCBF values and PANSS scores before and after the HPD dose showed positive correlations between the right inferior frontal gyrus and auditory hallucination or positive symptoms, between the right superior temporal gyrus, left thalamus and delusions, and between the left thalamus, insular gyrus and negative symptoms. These results suggest that acute drug-naive schizophrenic patients have widespread cortico-subcortical energic hypermetabolism and HPD reduces the hypermetabolism, leading to whole normalized brain metabolism, in particular with the larger region

Effects of typical antipsychotic, haloperidol on regional cerebral blood flow in drug-naive schizophrenic patients-study with 99mTc-HMPAO SPECT

Energy Technology Data Exchange (ETDEWEB)

Kamoya, Masatoshi [Kanazawa Medical Univ., Ishikawa (Japan)

2001-03-01

For the purpose of examining antipsychotic action of haloperidol (HPD), effects of chronic perioral administration of HPD 4.5 mg/day on regional cerebral blood flow (rCBF) with 99mTc-HMPAO SPECT were investigated in 12 drug-naive schizophrenic patients with acute hallucinatory and delusional state. Further, the SPECT examinations were performed on 20 normal adult volunteers to investigate differences in rCBFs between schizophrenics and the normal subjects. Results are itemized as follows. The rCBF values were significantly increased in the bilateral superior and middle frontal, cingulate, middle temporal, pre-and post-central gyri, the left superior temporal gyrus, the bilateral inferior parietal lobule, and the bilateral hippocampal and thalamic cortices in comparison between normal subjects and before the HPD dose in schizophrenics. However, the rCBF values after the HPD dose showed significant increases only in the bilateral pre-and post-central gyri in comparison with the normal subjects. The rCBF values were significantly decreased in the bilateral superior, middle and inferior frontal, superior and middle temporal gyri, and the left insular gyrus after the HPD dose in comparison with before the HPD dose. The psychiatric assessment with PANSS showed an improvement of positive symptoms consisting of auditory hallucination and delusions after the HPD dose. Statistical analyses on relationships between the rCBF values and PANSS scores before and after the HPD dose showed positive correlations between the right inferior frontal gyrus and auditory hallucination or positive symptoms, between the right superior temporal gyrus, left thalamus and delusions, and between the left thalamus, insular gyrus and negative symptoms. These results suggest that acute drug-naive schizophrenic patients have widespread cortico-subcortical energic hypermetabolism and HPD reduces the hypermetabolism, leading to whole normalized brain metabolism, in particular with the larger region

Associations between changes in city and address specific temperature and QT interval--the VA Normative Aging Study.

Directory of Open Access Journals (Sweden)

Amar J Mehta

Full Text Available BACKGROUND: The underlying mechanisms of the association between ambient temperature and cardiovascular morbidity and mortality are not well understood, particularly for daily temperature variability. We evaluated if daily mean temperature and standard deviation of temperature was associated with heart rate-corrected QT interval (QTc duration, a marker of ventricular repolarization in a prospective cohort of older men. METHODS: This longitudinal analysis included 487 older men participating in the VA Normative Aging Study with up to three visits between 2000-2008 (n = 743. We analyzed associations between QTc and moving averages (1-7, 14, 21, and 28 days of the 24-hour mean and standard deviation of temperature as measured from a local weather monitor, and the 24-hour mean temperature estimated from a spatiotemporal prediction model, in time-varying linear mixed-effect regression. Effect modification by season, diabetes, coronary heart disease, obesity, and age was also evaluated. RESULTS: Higher mean temperature as measured from the local monitor, and estimated from the prediction model, was associated with longer QTc at moving averages of 21 and 28 days. Increased 24-hr standard deviation of temperature was associated with longer QTc at moving averages from 4 and up to 28 days; a 1.9°C interquartile range increase in 4-day moving average standard deviation of temperature was associated with a 2.8 msec (95%CI: 0.4, 5.2 longer QTc. Associations between 24-hr standard deviation of temperature and QTc were stronger in colder months, and in participants with diabetes and coronary heart disease. CONCLUSION/SIGNIFICANCE: In this sample of older men, elevated mean temperature was associated with longer QTc, and increased variability of temperature was associated with longer QTc, particularly during colder months and among individuals with diabetes and coronary heart disease. These findings may offer insight of an important underlying mechanism of

Electroencephalographic changes in the lateral septum complex following systemic administration of DES-TYR1 -[alpha]-endorphin, Des-Tyr1-[gamma]-endorphin and haloperidol in rats

NARCIS (Netherlands)

Urban, I.J.A.; Wied, D. de

1982-01-01

The influence of systemically administered Des-Tyr1-α-endorphin (DTαE), Des-Tyr1-γ-endorphin (DTγE) and haloperidol on electroencephalographic (EEG) activity of the lateral septum complex (LSC) and the frontal cortex was studied in male rats. DTαE (2 μg) significantly increased whereas DTγE (10 μg)

Single-step synthesis of [18F]haloperidol from the chloro-precursor and its applications in PET imaging of a cat's brain

International Nuclear Information System (INIS)

Hashizume, Kazunari; Tamakawa, Hiroki; Hashimoto, Naoto; Miyake, Yoshihiro

1997-01-01

We have established a convenient synthesis process for the synthesis of [ 18 F]haloperidol using a single-step 18 F - for -Cl exchange reaction and a new elution system for the preparative high performance liquid chromatography (HPLC) using C18 bonded vinylalcohol copolymer gel (ODP) and a basic eluent. We successfully applied the product to cat-PET study and got clear images of the striatum, showing the usefulness of this synthesis. (author)

Developmental changes in FSH secretion induced by 5-hydroxytryptophan, naloxone and haloperidol in male and female rats.

Science.gov (United States)

Becú-Villalobos, D; Lacau-Mengido, I M; Libertun, C

1989-06-01

Follicle-stimulating hormone (FSH) secretion is increased in the immature female rat from day 5 to days 17-18 of life, and decreases steadily thereafter until puberty. It has been reported that estradiol negative feedback and inhibin-like peptides are low during this period, while luteinizing hormone (LH) and FSH sensitivity to LH-releasing hormone (LHRH) are maximal. It was therefore of interest to study the effects of some neurotropic drugs on FSH release at 12 days of age, and to compare their effects at 1 and 20 days. Besides, as developmental patterns and regulation of FSH are different in male and female rats, the experiments were carried out using male and female littermates. The drugs chosen were haloperidol, 5-hydroxytryptophan and naloxone. These drugs release LH in the infantile female rat, the effect decreasing or disappearing as the animal matures; no effects of these drugs have been reported on FSH release in infantile rats to the present time. It was found that haloperidol (0.25 mg/kg), naloxone (2 mg/kg) and 5-hydroxytryptophan (50 mg/kg) markedly increased the already high titers of FSH in the 12-day-old female rat. This effect could not be discerned in newborn rats, and had disappeared at 20 days of age. Male littermates failed to respond at any age. When adult male and female rats in diestrus were tested, all drugs at the chosen doses were ineffective in altering FSH release. These data suggest that the infantile female rat represents an interesting physiological model to evaluate the neural regulation of FSH in a situation in which inhibitory signals provided by inhibin and estrogen in later life are diminished.

Optimisation of Embryonic and Larval ECG Measurement in Zebrafish for Quantifying the Effect of QT Prolonging Drugs

Science.gov (United States)

Dhillon, Sundeep Singh; Dóró, Éva; Magyary, István; Egginton, Stuart; Sík, Attila; Müller, Ferenc

2013-01-01

Effective chemical compound toxicity screening is of paramount importance for safe cardiac drug development. Using mammals in preliminary screening for detection of cardiac dysfunction by electrocardiography (ECG) is costly and requires a large number of animals. Alternatively, zebrafish embryos can be used as the ECG waveform is similar to mammals, a minimal amount of chemical is necessary for drug testing, while embryos are abundant, inexpensive and represent replacement in animal research with reduced bioethical concerns. We demonstrate here the utility of pre-feeding stage zebrafish larvae in detection of cardiac dysfunction by electrocardiography. We have optimised an ECG recording system by addressing key parameters such as the form of immobilization, recording temperature, electrode positioning and developmental age. Furthermore, analysis of 3 days post fertilization (dpf) zebrafish embryos treated with known QT prolonging drugs such as terfenadine, verapamil and haloperidol led to reproducible detection of QT prolongation as previously shown for adult zebrafish. In addition, calculation of Z-factor scores revealed that the assay was sensitive and specific enough to detect large drug-induced changes in QTc intervals. Thus, the ECG recording system is a useful drug-screening tool to detect alteration to cardiac cycle components and secondary effects such as heart block and arrhythmias in zebrafish larvae before free feeding stage, and thus provides a suitable replacement for mammalian experimentation. PMID:23579446

Ocular Counter Rolling in Astronauts After Short- and Long-Duration Spaceflight.

Science.gov (United States)

Reschke, Millard F; Wood, Scott J; Clément, Gilles

2018-05-17

Ocular counter-rolling (OCR) is a reflex generated by the activation of the gravity sensors in the inner ear that stabilizes gaze and posture during head tilt. We compared the OCR measures that were obtained in 6 astronauts before, during, and after a spaceflight lasting 4-6 days with the OCR measures obtained from 6 astronauts before and after a spaceflight lasting 4-9 months. OCR in the short-duration fliers was measured using the afterimage method during head tilt at 15°, 30°, and 45°. OCR in the long-duration fliers was measured using video-oculography during whole body tilt at 25°. A control group of 7 subjects was used to compare OCR measures during head tilt and whole body tilt. No OCR occurred during head tilt in microgravity, and the response returned to normal within 2 hours of return from short-duration spaceflight. However, the amplitude of OCR was reduced for several days after return from long-duration spaceflight. This decrease in amplitude was not accompanied by changes in the asymmetry of OCR between right and left head tilt. These results indicate that the adaptation  of otolith-driven reflexes to microgravity is a long-duration process.

The effects of odour and body posture on perceived duration

Directory of Open Access Journals (Sweden)

Eliane eSchreuder

2014-02-01

Full Text Available This study reports an examination of the internal clock model, according to which subjective time duration is influenced by attention and arousal state. In a time production task, we examine the hypothesis that an arousing odour and an upright body posture affect perceived duration.The experimental task was performed while participants were exposed to an odour and either sitting upright (arousing condition or lying down in a relaxing chair (relaxing condition. They were allocated to one of three experimental odour conditions: rosemary (arousing condition, peppermint (relaxing condition and no odour (control condition. The predicted effects of the odours were not borne out by the results. Self-reported arousal and pleasure states were measured before, during (after each body posture condition and post experimentally. Heart rate and skin conductance were measured before and during the experiment. As expected, odour had an effect on perceived duration. When participants were exposed to rosemary odour, they produced significantly shorter time intervals than in the no odour condition. This effect, however, could not be explained by increased arousal. There was no effect of body posture on perceived duration, even though body posture did induce arousal. The results do not support the proposed arousal mechanism of the internal clock model.

Economic impact of antidepressant treatment duration in naturalistic conditions.

Science.gov (United States)

Tournier, M; Crott, R; Gaudron, Y; Verdoux, H

2013-05-01

To assess the economic impact of the duration of antidepressant drug treatment in a real-life setting. A historical fixed cohort study included 27 917 patients aged 18 and over with a new antidepressant treatment registered in the national insurance database. The economic impact concerned healthcare expenditure in the first 3 months after treatment discontinuation. Generalized linear models were used to compare two groups of treatment duration: adjustment for care costs before and during treatment episode, gender, age, chronic diseases, welfare and prescriber specialty, total healthcare costs (in log) [-0.06 (-0.14;0.01) P = 0.11] and psychiatric care costs (in square root) [-0.08 (-0.41;0.25) P = 0.6] were similar in both groups. Non-psychiatric care costs were significantly lower in the 'long treatment duration' group compared with the 'short treatment duration' group [-11.4 (-15.8; -7.0) P costs over the antidepressant treatment episode were larger in the 'long treatment duration' group compared with the 'short treatment duration' group. With regard to healthcare costs and global health, antidepressant drug treatments of short duration appear less effective than treatment of recommended duration. © 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

Different Functional and Microstructural Changes Depending on Duration of Mild Cognitive Impairment in Parkinson Disease.

Science.gov (United States)

Shin, N-Y; Shin, Y S; Lee, P H; Yoon, U; Han, S; Kim, D J; Lee, S-K

2016-05-01

The higher cortical burden of Lewy body and Alzheimer disease-type pathology has been reported to be associated with a faster onset of cognitive impairment of Parkinson disease. So far, there has been a few studies only about the changes of gray matter volume depending on duration of cognitive impairment in Parkinson disease. Therefore, our aim was to evaluate the different patterns of structural and functional changes in Parkinson disease with mild cognitive impairment according to the duration of parkinsonism before mild cognitive impairment. Fifty-nine patients with Parkinson disease with mild cognitive impairment were classified into 2 groups on the basis of shorter (parkinsonism before mild cognitive impairment. Fifteen drug-naïve patients with de novo Parkinson disease with intact cognition were included for comparison. Cortical thickness, Tract-Based Spatial Statistics, and seed-based resting-state functional connectivity analyses were performed. Age, sex, years of education, age at onset of parkinsonism, and levodopa-equivalent dose were included as covariates. The group with shorter duration of parkinsonism before mild cognitive impairment showed decreased fractional anisotropy and increased mean and radial diffusivity values in the frontal areas compared with the group with longer duration of parkinsonism before mild cognitive impairment (corrected P parkinsonism before mild cognitive impairment showed decreased resting-state functional connectivity in the default mode network area when the left or right posterior cingulate was used as a seed, and in the dorsolateral prefrontal areas when the left or right caudate was used as a seed (corrected P parkinsonism before mild cognitive impairment showed decreased resting-state functional connectivity mainly in the medial prefrontal cortex when the left or right posterior cingulate was used as a seed, and in the parieto-occipital areas when the left or right caudate was used as a seed (corrected P Parkinson

Comparison of the efficacy of carbamazepine, haloperidol and valproic acid in the treatment of children with Sydenham´s chorea: clinical follow-up of 18 patients Comparación de la eficacia de carbamazepina, haloperidol y acido valproico en el tratamiento de niños con corea de Sydenham: seguimiento clínico de 18 pacientes

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Joaquín Peña

2002-06-01

Full Text Available In order to compare and contrast the efficacy of haloperidol, carbamazepine, and valproic acid in the treatment of Sydenham´s chorea a prospective study including 18 cases of this disorder was undertaken. Age of patients ranged from 7 to 15 years. Ten children were female and 8 were male. All but one had generalized, either symmetric or asymmetric chorea. The patients were divided in three equal groups, and were given a standardized dose of each of the drugs built-up over a week. Following therapy, the six children receiving valproic acid showed remarkable improvement, without side effects. Five patients receiving carbamazepine showed improvement without side effects. Only three of the patients that received haloperidol improved. In the 4 cases that did not show clinical improvement after one week of treatment, therapy with valproic acid led to disappearance of the symptoms in a lapse that ranged from 4 to 7 days. Recurrence related to discontinuation of treatment was observed in two patients. In view of the present results we recommend valproic acid as the first choice drug to treat Sydenham chorea.A fin de comparar y contrastar la eficacia de haloperidol, carbamazepina y ácido valproico en el tratamiento de la corea de Sydenham, se realizó un estudio prospectivo que incluyó 18 casos de esta patología. La edad de los pacientes varió de 7 a 15 años. Diez de los niños eran varones y el resto hembras. A excepción de uno de ellos, todos tenían corea generalizada, simétrica ó asimétrica. Los pacientes fueron divididos en tres grupos iguales, a cada uno de los cuales se le administró una dosis estandarizada de los medicamentos mencionados durante una semana. Luego del tratamiento, los seis pacientes que recibieron ácido valproico mostraron mejoría notable sin efectos colaterales. Cinco de los seis pacientes que recibieron carbamazepina exhibieron mejoría sin efectos colaterales. Solo tres de los pacientes que recibieron haloperidol

帕利哌酮与氟哌啶醇治疗儿童抽动障碍对照研究%A Control Study of Paliperidone Versus Haloperidol in the Treatment of Tic Disorders in Children

Institute of Scientific and Technical Information of China (English)

陆志新; 石磊; 李志佳

2015-01-01

Objective To compare the efficacy and adverse reactions between Paliperidone and Haloperidol in the treatment of children with tic disorders(TD). Methods Sixty children of 8-16 years old with tic disorders admitted in our clinic from January 2012 to March 2014 were randomly assigned to Paliperidone group (n=30) and Haloperidol group (n=30), treated by Paliperidone and Haloperidol, respectively, for 8 weeks. The treatment efficacy and adverse reactions were measured by the Yale Global Tic Severity Scale (YGTSS) and the Treatment Emergent Symptom Scale (TESS) at the baseline, week 2, 4 and 8, respectively. Results After 2 weeks of treatment, the total tic scores measured by the YGTSS decreased in both groups, and the rate of YGTSS decreased in Paliperidone group was significantly higher than that in Haloperidol group. The overall rate of effectiveness after 8 weeks’ treatment was 90.0% and 66.7% in Paliperidone group and Haloperidol group, respectively(P<0.05). The incidence of adverse reactions after 8 weeks’treatment was 20.0% and 76.7% in Paliperidone group and Haloperidol group, respectively(P<0.01). Conclusion Both Paliperidone and Haloperidol can be used for children with tic disorders. However, Paliperidone may be a promising drug in the treatment of children with tic disorders because of its higher efficacy and less adverse reactions and better tolerance.%目的：比较利帕利哌酮与氟哌啶醇治疗儿童抽动障碍(tic disorders, TD)的疗效及不良反应。方法对该院2012年1月—2014年3月门诊收治的60例儿童抽动障碍患者(年龄8～16岁)随机分成两组,分别给予利帕利哌酮与氟哌啶醇,其中帕利哌酮组30例,氟哌啶醇组30例,疗程8周。分别采用耶鲁抽动症状严重程度量表(Yale Global Tic Severity Scale, YGTSS)和不良反应量表(treatment emergent symptom scale, TESS)对治疗前、治疗后第2、4、8�

Assessment of anti-arrhythmic activity of antipsychotic drugs in an animal model

DEFF Research Database (Denmark)

Mow, Tomas; Frederiksen, Kristen; Thomsen, Morten B.

2015-01-01

limited experimental information exists about the effects of α1-adrenergic receptor activity of antipsychotic drugs in pro-arrhythmic models, we have decided to investigate this. In this study we show that four antipsychotic drugs all have high affinity for α1-adrenergic receptor (sertindole>risperidone>haloperidol......>olanzapine) and all block IKr (sertindole>haloperidol>risperidone>olanzapine). In canine Purkinje fibres, α1-adrenergic stimulation prolonged action potential duration; however, the stimulation does not cause afterdepolarizations, even in the presence of dofetilide-induced delayed repolarization. We showed...

Cost effectiveness of long-acting risperidone injection versus alternative antipsychotic agents in patients with schizophrenia in the USA.

Science.gov (United States)

Edwards, Natalie C; Locklear, Julie C; Rupnow, Marcia F T; Diamond, Ronald J

2005-01-01

The availability of long-acting risperidone injection may increase adherence and lead to improved clinical and economic outcomes for individuals with schizophrenia. The objective of this study was to assess the cost effectiveness of long-acting risperidone, oral risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, and haloperidol depot in patients with schizophrenia over 1 year from a healthcare system perspective. Published medical literature, unpublished data from clinical trials and a consumer health database, and a clinical expert panel were utilized to populate a decision analytical model comparing the seven treatment alternatives. The model captured rates of patient compliance, the rates, frequency and duration of relapse, incidence of adverse events, and healthcare resource utilization and associated costs. Primary outcomes were expressed in terms of percentage of patients relapsing per year, number of relapse days per year (number and duration of relapses per patient per year), and total direct 2003 medical cost per patient per year. On the basis of model projections, the proportions of patients experiencing a relapse requiring hospitalization in 1 year were 66% for haloperidol depot, 41% for oral risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole, and 26% for long-acting risperidone, whereas the proportions of patients with an exacerbation not requiring hospitalization were 60% for haloperidol depot, 37% for oral risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole, and 24% for long-acting risperidone. The mean number of days of relapse requiring hospitalization per patient per year were 28 for haloperidol depot, 18 for oral risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole, and 11 for long-acting risperidone, whereas the mean number of days of exacerbation not requiring hospitalization were eight for haloperidol depot, five for oral risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole

Righting elicited by novel or familiar auditory or vestibular stimulation in the haloperidol-treated rat: rat posturography as a model to study anticipatory motor control.

Science.gov (United States)

Clark, Callie A M; Sacrey, Lori-Ann R; Whishaw, Ian Q

2009-09-15

External cues, including familiar music, can release Parkinson's disease patients from catalepsy but the neural basis of the effect is not well understood. In the present study, posturography, the study of posture and its allied reflexes, was used to develop an animal model that could be used to investigate the underlying neural mechanisms of this sound-induced behavioral activation. In the rat, akinetic catalepsy induced by a dopamine D2 receptor antagonist (haloperidol 5mg/kg) can model human catalepsy. Using this model, two experiments examined whether novel versus familiar sound stimuli could interrupt haloperidol-induced catalepsy in the rat. Rats were placed on a variably inclined grid and novel or familiar auditory cues (single key jingle or multiple key jingles) were presented. The dependent variable was movement by the rats to regain equilibrium as assessed with a movement notation score. The sound cues enhanced movements used to regain postural stability and familiar sound stimuli were more effective than unfamiliar sound stimuli. The results are discussed in relation to the idea that nonlemniscal and lemniscal auditory pathways differentially contribute to behavioral activation versus tonotopic processing of sound.

Single-step synthesis of [{sup 18}F]haloperidol from the chloro-precursor and its applications in PET imaging of a cat`s brain

Energy Technology Data Exchange (ETDEWEB)

Hashizume, Kazunari; Tamakawa, Hiroki; Hashimoto, Naoto; Miyake, Yoshihiro [National Cardiovascular Center, Suita (Japan). Inst. of Biofunctional Research

1997-09-01

We have established a convenient synthesis process for the synthesis of [{sup 18}F]haloperidol using a single-step {sup 18}F - for -Cl exchange reaction and a new elution system for the preparative high performance liquid chromatography (HPLC) using C18 bonded vinylalcohol copolymer gel (ODP) and a basic eluent. We successfully applied the product to cat-PET study and got clear images of the striatum, showing the usefulness of this synthesis. (author).

Reducing the time until psychotherapy initiation reduces sick leave duration in participants diagnosed with anxiety and mood disorders.

Science.gov (United States)

Alonso, Sandra; Marco, José H; Andani, Joaquín

2018-01-01

Sick leave in patients with a mental disorder is characterized by having a long duration. Studies suggest that the time until a patient on sick leave for a common mental health disorder initiates evaluation and treatment by a healthcare professional is an important factor in the duration of the sick leave. However, in these studies, the intervention was not performed by a mental health specialist. The aim of this study was to find out whether the length of sick leave was associated with the time before initiating psychotherapy, age, time until returning to work after psychotherapy ends, and duration of psychotherapy. In a further analysis, we examined whether the model composed of age, duration of psychotherapy, and time before initiating psychotherapy predicted the length of sick leave. The sample consisted of 2,423 participants, 64.1% (n = 1,554) women and 35.9% (n = 869) men, who were on sick leave for anxiety disorders or depressive disorder. The total duration of the sick leave of participants diagnosed with depression and anxiety was positively associated with the time before beginning psychotherapy. Time before beginning psychotherapy predicted the length of sick leave when the variables age and duration of psychotherapy were controlled. It is necessary to reduce the time until beginning psychotherapy in people on sick leave for common mental disorders. Copyright © 2017 John Wiley & Sons, Ltd.

Safety and efficacy of vemurafenib in end stage renal failure

International Nuclear Information System (INIS)

Iddawela, Mahesh; Crook, Sarah; George, Leah; Lakkaraju, Amit; Nanayakkara, Nihal; Hunt, Roland; Adam, William R

2013-01-01

Serine-threonine inhibitors, such as vemurafenib, are being used increasingly in cancer treatment, and the toxicity and therapeutic benefit need to be balanced carefully both before and during treatment. A patient with metastatic melanoma and end stage renal failure who was on peritoneal dialysis was treated with the serine-threonine kinase inhibitor, vemurafenib. After 5 months of treatment, a substantial response to vemurafenib was observed using imaging, but when he developed a prolonged QTc interval (common toxicity criteria (CTC) grade 3), treatment was interrupted. Vemurafenib was restarted at a reduced dose when the QTc interval returned to normal. The patient has had a significant response to vemurafenib and continued on treatment for 12 months after beginning the therapy. This is the first reported case of end stage renal failure in a patient who is taking vemurafenib. Although the patient developed QTc prolongation, it appears to be asymptomatic, and was managed with dose reduction. This case highlights the need for closer QTc monitoring at the start and during treatment

Valproic Acid and Sleep Duration in Children with Epilepsy

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J Gordon Millichap

2009-09-01

Full Text Available Sleep duration and behavior were assessed in 46 children (age range 1.7-17.4 years before and after tapering valproic acid (VPA administered for more than 6 months for epilepsy, in a study at University Children's Hospital, Zurich, Switzerland.

The adenosine A2A antagonist MSX-3 reverses the effects of the dopamine antagonist haloperidol on effort-related decision making in a T-maze cost/benefit procedure.

Science.gov (United States)

Mott, Allison M; Nunes, Eric J; Collins, Lyndsey E; Port, Russell G; Sink, Kelly S; Hockemeyer, Jörg; Müller, Christa E; Salamone, John D

2009-05-01

Mesolimbic dopamine (DA) is a critical component of the brain circuitry regulating behavioral activation and effort-related processes. Research involving choice tasks has shown that rats with impaired DA transmission reallocate their instrumental behavior away from food-reinforced tasks with high response requirements and instead select less effortful food-seeking behaviors. Previous work showed that adenosine A(2A) antagonism can reverse the effects of the DA antagonist haloperidol in an operant task that assesses effort-related choice. The present work used a T-maze choice procedure to assess the effects of adenosine A(2A) and A(1) antagonism. With this task, the two arms of the maze have different reinforcement densities (four vs. two food pellets), and a vertical 44 cm barrier is positioned in the arm with the higher density, presenting the animal with an effort-related challenge. Untreated rats strongly prefer the arm with the high density of food reward and climb the barrier in order to obtain the food. Haloperidol produced a dose-related (0.05-0.15 mg/kg i.p.) reduction in the number of trials in which the rats chose the high-barrier arm. Co-administration of the adenosine A(2A) receptor antagonist MSX-3 (0.75, 1.5, and 3.0 mg/kg i.p.), but not the A(1) antagonist 8-cyclopentyl-1,3-dipropylxanthine (0.75, 1.5, and 3.0 mg/kg i.p.), reversed the effects of haloperidol on effort-related choice and latency. Adenosine A(2A) and D2 receptors interact to regulate effort-related decision making, which may have implications for the treatment of psychiatric symptoms such as psychomotor slowing or anergia that can be observed in depression, parkinsonism, and other disorders.

Safety and effectiveness of drug therapy for the acutely agitated patient (Part I

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Gianluca Airoldi

2013-04-01

Full Text Available Acute agitation occurs in a variety of medical and psychiatric conditions, and the management of agitated, abusive, or violent patients is a common problem in the emergency department. Rapid control of potentially dangerous behaviors by physical restraint and pharmacologic tranquillization is crucial to ensure the safety of the patient and health-care personnel and to allow diagnostic procedures and treatment of the underlying condition. The purpose of this article (the first in a 2-part series is to review the extensive safety data published on the antipsychotic medications currently available for managing situations of this type, including older neuroleptics like haloperidol, chlorpromazine, and pimozide as well as a number of the newer atypical antipsychotics (olanzapine, risperidone, ziprasidone. Particular attention is focused on the ability of these drugs to lengthen the QT interval in surface electrocardiograms. This adverse effect is of major concern, especially in light of the reported relation between QT interval and the risk of sudden death. In patients with the congenital long-QT syndrome, a long QT interval is associated with a fatal paroxysmal ventricular arrhythmia knownas torsades de pointes. Therefore, careful evaluation of the QT-prolonging properties and arrhythmogenic potential of antipsychotic drugs is urgently needed. Clinical assessment of drug-induced QT-interval prolongation is strictly dependent on the quality of electrocardiographic data and the appropriateness of electrocardiographic analyses. Unfortunately, measurement imprecision and natural variability preclude a simple use of the actually measured QT interval as a surrogate marker of drug-induced proarrhythmia. Because the QT interval changes with heart rate, a rate-corrected QT interval (QTc is commonly used when evaluating a drug’s effect. In clinical settings, themost widely used formulas for rate-correction are those of Bazett (QTc=QT/RR^0.5 and Fridericia

Changes in Sleep Duration During Transition to Statutory Retirement: A Longitudinal Cohort Study.

Science.gov (United States)

Myllyntausta, Saana; Salo, Paula; Kronholm, Erkki; Aalto, Ville; Kivimäki, Mika; Vahtera, Jussi; Stenholm, Sari

2017-07-01

This study examined whether sleep duration changes during the transition from full-time work to statutory retirement and, if this were the case, which preretirement factors, including sociodemographic, work, lifestyle, and health factors, predict these changes. Data from repeated surveys of the Finnish Public Sector study, linked to records of retirement, were used. The study population consisted of 5785 participants who retired on a statutory basis in 2000-2011 and who had responded to surveys on sleep duration at least once immediately before and after their retirement (mean number of repeat study waves 3.6). Linear regression analyses with generalized estimating equations were used to examine changes in sleep duration around retirement. Before retirement there was a slight decrease in sleep duration. During the 4-year retirement transition, sleep duration increased from 7 hours 0 minutes (95% confidence interval [CI] 6 hours 54 minutes to 7 hours 6 minutes) to 7 hours and 22 minutes (95% CI 7 hours 16 minutes to 7 hours 27 minutes); thus, mean increase being 22 minutes. Increase in sleep duration was greatest in those who were short sleepers, heavy drinkers, or had sleep difficulties. After the retirement transition, sleep duration remained at approximately the same level, as no significant changes were observed. This longitudinal study suggests that transition from full-time work to statutory retirement is associated with an increase in sleep duration. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Duration of patients’ visits to the hospital emergency department

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Karaca Zeynal

2012-11-01

Full Text Available Abstract Background Length of stay is an important indicator of quality of care in Emergency Departments (ED. This study explores the duration of patients’ visits to the ED for which they are treated and released (T&R. Methods Retrospective data analysis and multivariate regression analysis were conducted to investigate the duration of T&R ED visits. Duration for each visit was computed by taking the difference between admission and discharge times. The Healthcare Cost and Utilization Project (HCUP State Emergency Department Databases (SEDD for 2008 were used in the analysis. Results The mean duration of T&R ED visit was 195.7 minutes. The average duration of ED visits increased from 8 a.m. until noon, then decreased until midnight at which we observed an approximately 70-minute spike in average duration. We found a substantial difference in mean duration of ED visits (over 90 minutes between Mondays and other weekdays during the transition time from the evening of the day before to the early morning hours. Black / African American patients had a 21.4-minute longer mean duration of visits compared to white patients. The mean duration of visits at teaching hospitals was substantially longer than at non-teaching hospitals (243.8 versus 175.6 minutes. Hospitals with large bed size were associated with longer duration of visits (222.2 minutes when compared to hospitals with small bed size (172.4 minutes or those with medium bed size (166.5 minutes. The risk-adjusted results show that mean duration of visits on Mondays are longer by about 4 and 9 percents when compared to mean duration of visits on non-Monday workdays and weekends, respectively. Conclusions The duration of T&R ED visits varied significantly by admission hour, day of the week, patient volume, patient characteristics, hospital characteristics and area characteristics.

Supersensitivity of GABAergic systems induced within rat substantia nigra and globus pallidus by haloperidol

International Nuclear Information System (INIS)

Frey, J.J.M.

1986-01-01

The supersensitivity was demonstrated by an increase in the responsiveness of individual neurons within these brain regions to microiontophoretically-applied GABA and by an up regulation of GABA binding sites. Rates received haloperidol for 30 days in their feed and were then withdrawn from treatment for 48 hrs. 3 H-GABA binding was found to be significantly elevated with the SN R (55%) and GP (42%). Scatchard analysis of 3 H-muscimol binding isotherms indicated that the number (B max ) of high affinity binding sites within the GP was significantly increased (32%); within the SN R , significant increases were detected in the B max of both high (23%) and low (58%) affinity 3 H-muscimol binding sites. After CHAL treatment, signs of dopaminergic supersensitivity within the basal ganglia were also observed. Spontaneous locomotor activity and apomorphine-induced stereotyped behavior were increased and specific 3 H-spiroperidol binding was elevated within the striatum (60%) and GP (236%)

Loss-of-activity-mutation in the cardiac chloride-bicarbonate exchanger AE3 causes short QT syndrome

DEFF Research Database (Denmark)

Thorsen, Kasper; Dam, Vibeke S.; Kjaer-Sorensen, Kasper

2017-01-01

unrelated families with SQTS. The mutation causes reduced surface expression of AE3 and reduced membrane bicarbonate transport. Slc4a3 knockdown in zebrafish causes increased cardiac pHi, short QTc, and reduced systolic duration, which is rescued by wildtype but not mutated SLC4A3. Mechanistic analyses...

Analysis of Relationship between Levofloxacin and Corrected QT Prolongation Using a Clinical Data Warehouse.

Science.gov (United States)

Park, Man Young; Kim, Eun Yeob; Lee, Young Ho; Kim, Woojae; Kim, Ku Sang; Sheen, Seung Soo; Lim, Hong Seok; Park, Rae Woong

2011-03-01

The aim of this study was to examine whether or not levofloxacin has any relationship with QT prolongation in a real clinical setting by analyzing a clinical data warehouse of data collected from different hospital information systems. Electronic prescription data and medical charts from 3 different hospitals spanning the past 9 years were reviewed, and a clinical data warehouse was constructed. Patients who were both administrated levofloxacin and given electrocardiograms (ECG) were selected. The correlations between various patient characteristics, concomitant drugs, corrected QT (QTc) prolongation, and the interval difference in QTc before and after levofloxacin administration were analyzed. A total of 2,176 patients from 3 different hospitals were included in the study. QTc prolongation was found in 364 patients (16.7%). The study revealed that age (OR 1.026, p data seem to be essential to adverse drug reaction surveillance in future.

Duration of increased bleeding tendency after cessation of aspirin therapy.

LENUS (Irish Health Repository)

Cahill, Ronan A

2012-02-03

BACKGROUND: Aspirin has a significant effect on hemostasis, so it is often recommended that patients taking aspirin discontinue treatment before elective surgery. While off aspirin, these patients may be at risk of thrombosis. The optimum period of time that aspirin should be withheld is controversial. The aim of this study was to establish the duration of the antihemostatic effect of prolonged aspirin therapy. STUDY DESIGN: In a prospective study, 51 healthy volunteers were randomly assigned into 3 groups, each receiving an identical tablet for 14 days. One group received a placebo tablet; individuals in the other two groups received either 75 mg or 300 mg of aspirin once a day. Template bleeding times and specific platelet function testing (using the PFA-100; Dade Behring) were carried out on subjects before therapy and again after its completion until they returned to baseline. RESULTS: Thirty-eight volunteers complied sufficiently with the protocol to provide useful results. All bleeding times normalized within 96 hours and all platelet function tests within 144 hours after stopping aspirin. There was no demonstrable hemostatic defect in any volunteer persisting by or beyond the sixth day after treatment cessation. There was no apparent difference in duration of effect between those taking either 75 mg or 300 mg of aspirin. CONCLUSIONS: This study uses sensitive measures of platelet function to demonstrate the duration of increased bleeding tendency after withdrawal of aspirin therapy. It supports discontinuation of aspirin therapy 5 days before elective surgery (with the operation being performed on the sixth day).

Cost-effectiveness of an atypical conventional antipsychotic in South Africa: An economic evaluation of quetiapine versus haloperidol in the treatment of patients partially responsive to previous antipsychotics

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Robin Emsley

2004-10-01

Full Text Available Background. The introduction of a new generation of atypical antipsychotic agents has raised difficult economic and ethical questions, particularly in lower-income countries. The reported tolerability and efficacy advantages of the atypical antipsy- chotics over their conventional predecessors have to be weighed against their higher acquisition costs. Pharmaco-eco- nomic studies conducted in Western countries consistently report cost advantages or cost neutrality for these new agents. However, considerable differences in health care service pro- vision make it difficult to generalise these findings to South Africa. Method. We compared the direct costs (private and public sector of treating schizophrenia with an atypical antipsychotic quetiapine, and with a conventional antipsychotic haloperidol, by adapting a decision-analytic pharmaco-economic model for South African circumstances. The sample comprised patients partially responsive to antipsychotics, who had partic- ipated in a multinational randomised controlled trial compar- ing the efficacy and safety of quetiapine versus haloperidol. Results. The estimated total direct cost for the treatment with quetiapine in South Africa was slightly less than for haloperidol for various models in both the private and the public sectors. Conclusions. Significant differences in health care provision make pharmaco-economic studies conducted in other coun- tries invalid for South African circumstances. Previously queti- apine treatment did not result in direct cost savings in South Africa. However, the recently introduced legislation to estab- lish single exit prices for medications has resulted in the cost of quetiapine treatment declining by 36.7% and that of haloperi- dol by 13%. This has translated into an overall direct cost sav- ing for quetiapine in both the private and public sector models. This, together with additional indirect advantages of the atypi- cal antipsychotics such as improved quality of

Predicting the phytoextraction duration to remediate heavy metal contaminated soils

NARCIS (Netherlands)

Koopmans, G.F.; Römkens, P.F.A.M.; Song, J.; Temminghoff, E.J.M.; Japenga, J.

2007-01-01

The applicability of phytoextraction to remediate soils contaminated with heavy metals (HMs) depends on, amongst others, the duration before remediation is completed. The impact of changes in the HM content in soil occurring during remediation on plant uptake has to be considered in order to obtain

Pharmacological evaluation of bee venom and melittin

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Camila G. Dantas

Full Text Available The objective of this study was to identify the pharmacological effects of bee venom and its major component, melittin, on the nervous system of mice. For the pharmacological analysis, mice were treated once with saline, 0.1 or 1.2 mg/kg of bee venom and 0.1 mg/kg of melittin, subcutaneously, 30 min before being submitted to behavioral tests: locomotor activity and grooming (open-field, catalepsy, anxiety (elevated plus-maze, depression (forced swimming test and apomorphine-induced stereotypy. Haloperidol, imipramine and diazepam were administered alone (positive control or as a pre-treatment (haloperidol.The bee venom reduced motor activity and promoted cataleptic effect, in a similar manner to haloperidol.These effects were decreased by the pretreatment with haloperidol. Both melittin and bee venom decreased the apomorphine-induced stereotypies. The data indicated the antipsychotic activity of bee venom and melittin in a murine model.

Autoradiographic analysis of regional alterations in brain receptors following chronic administration and withdrawal of typical and atypical neuroleptics in rats

International Nuclear Information System (INIS)

See, R.E.; Ellison, G.; Toga, A.W.

1990-01-01

Rats were administered haloperidol, clozapine, raclopride, or no drug for 28 days or 8 months. Following a 3 week withdrawal period, in vitro autoradiography was utilized to examine receptor binding for dopamine D2([ 3 H]spiperone and [ 3 H]raclopride), dopamine D1([ 3 H]SCH23390), GABA A ([ 3 H]muscimol), benzodiazepine ([ 3 H]RO15-1788), and muscarinic ACh receptors ([ 3 H]QNB). [ 3 H]spiperone was elevated in striatal subregions only in haloperidol-treated rats, with the largest increases seen in the 8 month duration animals. Striatal [ 3 H]raclopride binding was increased after both short- and long-term treatment in both haloperidol and raclopride, but not clozapine-treated animals. Clozapine-treated rats showed significant increases in [ 3 H]SCH23390 in the nucleus accumbens after 28-day administration; otherwise no changes were seen for this ligand in any other groups. Increases in [ 3 H]muscimol binding in the substantia nigra reticulata were seen in haloperidol-treated rats after 8 month treatment. Binding of [ 3 H]QNB and [ 3 H]RO15-1788 were not significantly different from control for any of the drug-treated groups. These data suggest that persisting alterations in receptor binding are primarily seen in dopamine D2 and GABA receptors after withdrawal from chronic administration of haloperidol but not the atypical neuroleptics, clozapine and raclopride. (Authors)

Efeitos de esmolol, lidocaína e fentanil nos intervalos dispersão da onda P, QT, QTc e respostas hemodinâmicas à intubação endotraqueal durante indução com propofol: um estudo comparativo

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Volkan Hancı

2013-06-01

Full Text Available JUSTIFICATIVA E OBJETIVOS: Investigar o efeito de esmolol, lidocaína e fentanil na dispersão da onda P (DP, durações dos intervalos QT e QT corrigido (QTc e as respostas hemodinâmicas à intubação endotraqueal durante a indução com propofol. MÉTODOS: Foram incluídos 80 pacientes adultos, estado físico ASA I ou II, idade entre 18 e 60 anos, neste estudo prospectivo, randômico e duplo-cego. Todos os pacientes foram submetidos a exame eletrocardiográfico (ECG antes da indução da anestesia. Os pacientes foram randomicamente alocados em quatro grupos iguais. O grupo controle (Grupo C recebeu 5 mL de solução salina; o grupo esmolol (Grupo E recebeu 0,5 mg.kg-1 de esmolol; o grupo fentanil (Grupo F recebeu 2 µg.kg-1 de fentanil e o grupo lidocaína (Grupo L recebeu 1,5 mg.kg-1 de lidocaína antes da indução anestésica. A anestesia foi induzida com propofol. ECG foi feito em todos os pacientes durante o primeiro e o terceiro minutos de indução, 3 minutos após a administração de relaxante muscular e 5 e 10 minutos após intubação. A DP e intervalos QT foram medidos em todos os ECGs. Os intervalos QTc foram determinados com o uso da fórmula de Bazett. Frequência cardíaca (FC e pressão arterial média (PAM foram registradas antes e depois da indução anestésica, imediatamente após a intubação e em 1, 3, 5, 7 e 10 minutos após a intubação. RESULTADOS: Após a intubação, a FC aumentou significativamente nos Grupos C, L e F em comparação com o grupo controle. Porém, não houve diferença significativa nos valores da FC após a intubação entre os grupos E e controle. Nos Grupos C e L, a PAM aumentou significativamente após a intubação em comparação com o grupo controle. No entanto, nos Grupos L, F e E não houve diferença significativa entre os valores da PAM após a intubação em comparação com o grupo controle. A DP foi significativamente mais longa no Grupo C após a intubação em comparação com o

Evaluation of σ-1 receptor radioligand 18F-FTC-146 in rats and squirrel monkeys using PET

DEFF Research Database (Denmark)

James, Michelle L; Shen, Bin; Nielsen, Carsten Haagen

2014-01-01

. Pretreatment with known S1R compounds, haloperidol, or BD1047, before radioligand administration, significantly attenuated (18)F-FTC-146 accumulation in all rat brain regions by approximately 85% (P ...-FTC-146 was observed in rat plasma. Preliminary monkey PET/MRI studies demonstrated specific accumulation of (18)F-FTC-146 in the brain (mainly in cortical structures, cerebellum, and vermis) that could be attenuated by pretreatment with haloperidol. HPLC of monkey plasma suggested radioligand metabolism...

(125I)Iodoazidococaine, a photoaffinity label for the haloperidol-sensitive sigma receptor

International Nuclear Information System (INIS)

Kahoun, J.R.; Ruoho, A.E.

1992-01-01

A carrier-free radioiodinated cocaine photoaffinity label, (-)-3-( 125 I)iodo-4-azidococaine [( 125 I)IACoc], has been synthesized and used as a probe for cocaine-binding proteins. Photoaffinity labeling with 0.5 nM ( 125 I)IACoc resulted in selective derivatization of a 26-kDa polypeptide with the pharmacology of a sigma receptor in membranes derived from whole rat brain, rat liver, and human placenta. ( 125 I)IACoc labeling of the 26-kDa polypeptide was also inhibited by 10 μM imipramine, amitriptyline, fluoxetine, benztropine, and tetrabenazine. The size of the ( 125 I)I-ACoc-labeled proteins is consistent with the size of proteins photolabeled in guinea pig brain and liver membranes by using the sigma photolabel azido-[ 3 H]DTG. Kinetic analysis of ( 125 I)IACoc binding to rat liver microsomes revealed two sites with K d values of 19 and 126 pM, respectively. The presence or absence of proteolytic inhibitors during membrane preparation did not alter the size of the photolabeled sigma receptor, indicating that the 26-kDa polypeptide was not derived from a larger protein. In summary, ( 125 I)IACoc is a potent and highly specific photoaffinity label for the haloperidol-sensitive sigma receptor and will be useful for its biochemical and molecular characterization

Comparative study between two animal models of extrapyramidal movement disorders: prevention and reversion by pecan nut shell aqueous extract.

Science.gov (United States)

Trevizol, Fabiola; Benvegnú, Dalila M; Barcelos, Raquel C S; Pase, Camila S; Segat, Hecson J; Dias, Verônica Tironi; Dolci, Geisa S; Boufleur, Nardeli; Reckziegel, Patrícia; Bürger, Marilise E

2011-08-01

Acute reserpine and subchronic haloperidol are animal models of extrapyramidal disorders often used to study parkinsonism, akinesia and tardive dyskinesia. In humans, these usually irreversible and disabling extrapyramidal disorders are developed by typical antipsychotic treatment, whose pathophysiology has been related to oxidative damages development. So far, there is no treatment to prevent these problems of the psychiatric clinic, and therefore further studies are needed. Here we used the animal models of extrapyramidal disorders cited above, which were performed in two distinct experiments: orofacial dyskinesia (OD)/catalepsy induced by acute reserpine and subchronic haloperidol after (experiment 1) and before (experiment 2) oral treatment with pecan shell aqueous extract (AE), a natural and promissory antioxidant. When administered previously (exp.1), the AE prevented OD and catalepsy induced by both reserpine and haloperidol. When reserpine and haloperidol were administered before the extract (exp.2), the animals developed OD and catalepsy all the same. However, the orofacial parameter (but not catalepsy) in both animal models was reversed after 7 and 14 days of AE treatment. These results indicate that, acute reserpine and subchronic haloperidol administrations induced similar motor disorders, although through different mechanisms, and therefore are important animal models to study the physiopathology of extrapyramidal disorders. Comparatively, the pecan shell AE was able to both prevent and reverse OD but only to prevent catalepsy. These results reinforce the role of oxidative stress and validate the two animal models used here. Our findings also favor the idea of prevention of extrapyramidal disorders, rather than their reversal. Copyright © 2011 Elsevier B.V. All rights reserved.

Arousal and exposure duration affect forward step initiation

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Daniëlle eBouman

2015-11-01

Full Text Available Emotion influences parameters of goal-directed whole-body movements in several ways. For instance, previous research has shown that approaching (moving toward pleasant stimuli is easier compared to approaching unpleasant stimuli. However, some studies found that when emotional pictures are viewed for a longer time, approaching unpleasant stimuli may in fact be facilitated. The effect of viewing duration may modulate whole-body approach movement in previous research but this has not been investigated before. In the current study, participants initiated a step forward after viewing neutral, high-arousal pleasant and high-arousal unpleasant stimuli. The viewing duration of the stimuli was set to 7 different durations, varying from 100 to 4000ms. Valence and arousal scores were collected for all stimuli.The results indicate that both viewing duration and the arousal of the stimuli influence kinematic parameters in forward gait initiation. Specifically, longer viewing duration, compared to shorter viewing duration, (a diminished the step length and peak velocity in both neutral and emotional stimuli, (b increased reaction time in neutral stimuli and, (c decreased reaction time in pleasant and unpleasant stimuli. Strikingly, no differences were found between high-arousal pleasant and high-arousal unpleasant stimuli. In other words, the valence of the stimuli did not influence kinematic parameters of forward step initiation. In contrast, the arousal level (neutral: low; pleasant and unpleasant: high explained the variance found in the results. The kinematics of forward gait initiation seemed to be reflected in the subjective arousal scores, but not the valence scores. So it seems arousal affects forward gait initiation parameters more strongly than valence. In addition, longer viewing duration seemed to cause diminished alertness, affecting GI parameters. These results shed new light on the prevailing theoretical interpretations regarding approach

Association of Sleep Duration with Obesity among US High School Students

Directory of Open Access Journals (Sweden)

Richard Lowry

2012-01-01

Full Text Available Increasing attention is being focused on sleep duration as a potential modifiable risk factor associated with obesity in children and adolescents. We analyzed data from the national Youth Risk Behavior Survey to describe the association of obesity (self-report BMI ≥95th percentile with self-reported sleep duration on an average school night, among a representative sample of US high school students. Using logistic regression to control for demographic and behavioral confounders, among female students, compared to 7 hours of sleep, both shortened (≤4 hours of sleep; adjusted odds ratio (95% confidence interval, AOR = 1.50 (1.05–2.15 and prolonged (≥9 hours of sleep; AOR = 1.54 (1.13–2.10 sleep durations were associated with increased likelihood of obesity. Among male students, there was no significant association between obesity and sleep duration. Better understanding of factors underlying the association between sleep duration and obesity is needed before recommending alteration of sleep time as a means of addressing the obesity epidemic among adolescents.

The effect of high energy electron irradiation on blood-brain barrier permeability to haloperidol and stobadin in rats

Energy Technology Data Exchange (ETDEWEB)

Trnovec, T; Kallay, Z [Komenskeho Univ., Bratislava (Czechoslovakia). Inst. of Preventive and Clinical Medicine; Volenec, K [Karlova Univ., Hradec Kralove (Czechoslovakia). Lekarska Fakulta; Bezek, S; Durisova, M; Scasnar, V; Kubu, M [Slovenska Akademia Vied, Bratislava (Czechoslovakia). Ustav Experimentalnej Farmakologie; Svoboda, V [Medical Academy J.E. Purkyne, Hradec Kralove (Czechoslovakia)

1991-10-01

The heads of rats were irradiated by 4 MeV electrons in doses 90, 180, and 360 Gy. The observed times of deaths ranged 120-600, 60-420, and 150-370 min after 90, 180, and 360 Gy, respectively. A dose dependent decrease of the brain uptake index of haloperidol was observed 1 and 3 h post radiation. On the other hand an increased brain uptake index was found for stobadin after head irradiation with doses of 180 and 360 Gy. Regional cerebral blood flow, blood pressure, and heart rate were not significantly altered in the period following irradiation with 180 Gy. The observed changes in blood-brain barrier (BBB) permeability seem to be the result of the damaged function of morphological structures forming the BBB rather than altered regional blood flow. (orig.).

Single therapeutic and supratherapeutic doses of sacubitril/valsartan (LCZ696) do not affect cardiac repolarization.

Science.gov (United States)

Langenickel, Thomas H; Jordaan, Pierre; Petruck, Jesika; Kode, Kiran; Pal, Parasar; Vaidya, Soniya; Chandra, Priya; Rajman, Iris

2016-08-01

Sacubitril/valsartan (LCZ696) is a first-in-class angiotensin receptor neprilysin inhibitor (ARNI) indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure (NYHA class II-IV) and reduced ejection fraction. This study was aimed to evaluate the effect of single oral therapeutic (400 mg) and supratherapeutic (1200 mg) doses of LCZ696 on cardiac repolarization. This randomized double-blind crossover study in healthy male subjects compared the effect of therapeutic and supratherapeutic doses of LCZ696 with placebo and moxifloxacin 400 mg (open-label treatment) as positive control. The primary assessment was mean baseline- and placebo-corrected QTcF (∆∆QTcF; Fridericia correction). Additional assessments included the ∆∆QTcB (Bazett's correction), PR interval, QRS duration, heart rate (HR), LCZ696 pharmacokinetics, pharmacokinetic/pharmacodynamic relationships, and safety. Of the 84 subjects enrolled, 81 completed the study. The maximum upper bound of the two-sided 90 % confidence interval for ∆∆QTcF for LCZ696 400 mg and 1200 mg were <10 ms, and assay sensitivity was confirmed with moxifloxacin. No relevant treatment-emergent changes were observed in any of the ECG-derived parameters with LCZ696 or placebo, and the incidence of adverse events was comparable among the treatment groups. Single therapeutic and supratherapeutic doses of LCZ696 did not affect cardiac repolarization as defined by the E14 ICH guidelines.

Speaker-Sex Discrimination for Voiced and Whispered Vowels at Short Durations.

Science.gov (United States)

Smith, David R R

2016-01-01

Whispered vowels, produced with no vocal fold vibration, lack the periodic temporal fine structure which in voiced vowels underlies the perceptual attribute of pitch (a salient auditory cue to speaker sex). Voiced vowels possess no temporal fine structure at very short durations (below two glottal cycles). The prediction was that speaker-sex discrimination performance for whispered and voiced vowels would be similar for very short durations but, as stimulus duration increases, voiced vowel performance would improve relative to whispered vowel performance as pitch information becomes available. This pattern of results was shown for women's but not for men's voices. A whispered vowel needs to have a duration three times longer than a voiced vowel before listeners can reliably tell whether it's spoken by a man or woman (∼30 ms vs. ∼10 ms). Listeners were half as sensitive to information about speaker-sex when it is carried by whispered compared with voiced vowels.

Workplace Social Support and Behavioral Health Prior to Long-Duration Spaceflight.

Science.gov (United States)

Deming, Charlene A; Vasterling, Jennifer J

2017-06-01

Preparation and training for long-duration spaceflight bring with them psychosocial stressors potentially affecting the well-being and performance of astronauts, before and during spaceflight. Social support from within the workplace may mitigate behavioral health concerns arising during the preflight period and enhance resiliency before and during extended missions. The purpose of this review was to evaluate evidence addressing the viability of workplace social support as a pre-mission countermeasure, specifically addressing: 1) the observed relationships between workplace social support and behavioral health; 2) perceived need, acceptability, and format preference for workplace social support among high-achievers; 3) potential barriers to delivery/receipt of workplace social support; 4) workplace social support interventions; and 5) delivery timeframe and anticipated duration of workplace social support countermeasure benefits. We conducted an evidence review examining workplace social support in professional contexts sharing one or more characteristics with astronauts and spaceflight. Terms included populations of interest, social support constructs, and behavioral health outcomes. Abstracts of matches were subsequently reviewed for relevance and quality. Research findings demonstrate clear associations between workplace social support and behavioral health, especially following exposure to stress. Further, studies indicate strong need for support and acceptability of support countermeasures, despite barriers. Our review revealed two general formats for providing support (i.e., direct provision of support and training to optimize skills in provision and receipt of support) with potential differentiation of expected duration of benefits, according to format. Workplace social support countermeasures hold promise for effective application during pre-mission phases of long-duration spaceflight. Specific recommendations are provided.Deming CA, Vasterling JJ

Estudo da sístole elétrica ventricular nos insuficientes renais crônicos hemodialisados Study of ventricular electrical systole in patients with end-stage kidney disease on hemodialysis

Directory of Open Access Journals (Sweden)

Bruno Valentim

2013-03-01

and intermittent character of dialysis. Changes in ventricular electrical systole induced by necessary dialysis significantly contribute to predict sudden death due to arrhythmia in ESKD. OBJECTIVE: The major objective of this study was to assess the behavior of ventricular repolarization in dialysis by analyzing QTc interval and QTc dispersion. METHODS: This study sample consisted of 47 patients undergoing hemodialysis (61.7% males and 38.3% females, whose mean age was 66.79±13.16 years. All of them underwent three electrocardiograms performed before, during and after one dialysis session. Ventricular electrical systole was analyzed later. RESULTS: An increase in maximum QTc interval and QTc dispersion associated with dialysis was observed. In addition, an increase in the number of individuals meeting the electrocardiographic criteria for left ventricular hypertrophy (LVH was observed. After dialysis, higher means of the maximum QTc interval (473 ± 27.63 mseg and of the QTc dispersion (58.95 ± 18.87 mseg were observed in individuals with LVH as compared with those in individuals without LVH (455.21 ± 26.85 mseg and 44 ± 16.41 mseg, respectively. CONCLUSION: This study confirmed an increase in the QTc interval and QTc dispersion associated with dialysis. That emphasizes the dependence of ventricular repolarization on fluid and electrolyte balance, and suggests a profile of higher vulnerability to arrhythmia associated with dialysis .

Effects of SKF-83566 and haloperidol on performance on progressive ratio schedules maintained by sucrose and corn oil reinforcement: quantitative analysis using a new model derived from the Mathematical Principles of Reinforcement (MPR).

Science.gov (United States)

Olarte-Sánchez, C M; Valencia-Torres, L; Cassaday, H J; Bradshaw, C M; Szabadi, E

2013-12-01

Mathematical models can assist the interpretation of the effects of interventions on schedule-controlled behaviour and help to differentiate between processes that may be confounded in traditional performance measures such as response rate and the breakpoint in progressive ratio (PR) schedules. The effects of a D1-like dopamine receptor antagonist, 8-bromo-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol hydrobromide (SKF-83566), and a D2-like receptor antagonist, haloperidol, on rats' performance on PR schedules maintained by sucrose and corn oil reinforcers were assessed using a new model derived from Killeen's (Behav Brain Sci 17:105-172, 1994) Mathematical Principles of Reinforcement. Separate groups of rats were trained under a PR schedule using sucrose or corn oil reinforcers. SKF-83566 (0.015 and 0.03 mg kg(-1)) and haloperidol (0.05 and 0.1 mg kg(-1)) were administered intraperitoneally (five administrations of each treatment). Running and overall response rates in successive ratios were analysed using the new model, and estimates of the model's parameters were compared between treatments. Haloperidol reduced a (the parameter expressing incentive value) in the case of both reinforcers, but did not affect the parameters related to response time and post-reinforcement pausing. SKF-83566 reduced a and k (the parameter expressing sensitivity of post-reinforcement pausing to the prior inter-reinforcement interval) in the case of sucrose, but did not affect any of the parameters in the case of corn oil. The results are consistent with the hypothesis that blockade of both D1-like and D2-like receptors reduces the incentive value of sucrose, whereas the incentive value of corn oil is more sensitive to blockade of D2-like than D1-like receptors.

Ketamine-induced behavioural and brain oxidative changes in mice: an assessment of possible beneficial effects of zinc as mono- or adjunct therapy.

Science.gov (United States)

Onaolapo, Olakunle James; Ademakinwa, Olayemi Quyyom; Olalekan, Temitayo Opeyemi; Onaolapo, Adejoke Yetunde

2017-09-01

We studied the influence of zinc, haloperidol or olanzapine on neurobehaviour (open-field, radial arm maze and elevated plus maze) and brain antioxidant status in vehicle- or ketamine-treated mice, with the aim of ascertaining the potentials of zinc in counteracting ketamine's effects. Experiment 1 assessed the effects of zinc in healthy animals and the relative degrees of modulation of ketamine's effects by zinc, haloperidol or olanzapine, respectively. Experiment 2 assessed the modulation of ketamine's effects following co-administration of zinc with haloperidol or olanzapine. Male mice weighing 18-20 g each were used. Animals were pretreated with ketamine (except vehicle, zinc, haloperidol and olanzapine controls) for 10 days before commencement of 14-day treatment (day 11-24) with vehicle, zinc, haloperidol or olanzapine (alone or in combination). Ketamine injection also continued alongside zinc and/or standard drugs in the ketamine-treated groups. Zinc, haloperidol and olanzapine were administered by gavage. Treatments were given daily and behaviours assessed on days 11 and 24. On day 24, animals were sacrificed and whole brain homogenates used for estimation of glutathione, nitric oxide and malondialdehyde (MDA) levels. Ketamine increased open-field behaviours, nitric oxide and MDA levels, while it decreased working memory, social interaction and glutathione. Administration of zinc alone or in combination with haloperidol or olanzapine was associated with variable degrees of reversal of these effects. Zinc may have the potential of a possible therapeutic agent and/or adjunct in the reversal of schizophrenia-like changes in behaviour and brain oxidative status.

A associação de haloperidol, dexametasona e ondansetrona reduz a intensidade de náusea, dor e consumo de morfina após gastrectomia vertical laparoscópica

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Márcio Luiz Benevides

2013-10-01

Full Text Available JUSTIFICATIVA E OBJETIVOS: Náusea e vômito pós-operatório (NVPO ocorrem frequentemente após cirurgia bariátrica laparoscópica. A associação de haloperidol, dexametasona e ondansetrona pode reduzir esses eventos indesejáveis. O objetivo deste estudo foi avaliar a intensidade de náusea e dor, o número de episódios de vômito e o consumo de morfina no pós-operatório (PO de pacientes obesos submetidos à gastrectomia vertical laparoscópica (GVL. MÉTODO: Estudo clínico, aleatorizado, controlado e duplamente encoberto feito em 90 pacientes com índice de massa corporal > 35 kg.cm-2. Os pacientes foram distribuídos em três grupos de 30 para receberem no Grupo O: ondansetron 8 mg; no Grupo DO: ondansetron 8 mg e dexametasona 8 mg e no Grupo HDO: ondansetron 8 mg, dexametasona 8 mg e haloperidol 2 mg. Foram avaliados a intensidade de náusea e dor, por meio de escala numérica verbal, o número cumulativo de episódios de vômito e o consumo de morfina no período de 0-2, 2-12, 12-24 e 24-36 horas de PO. RESULTADOS: A intensidade de náusea foi menor no Grupo HDO comparado com o Grupo O (p = 0,001, a intensidade da dor foi menor no Grupo HDO comparado com o Grupo O (p = 0,046 e o consumo de morfina no Grupo HDO foi menor do que no Grupo O (p = 0,037. Não houve diferença do número de episódios de vômito entre os grupos (p = 0,052. CONCLUSÃO: A associação de haloperidol, dexametasona e ondansetron promoveu redução da intensidade de náusea, da dor e do consumo de morfina no PO de pacientes obesos submetidos à GVL.

Autoradiographic analysis of regional alterations in brain receptors following chronic administration and withdrawal of typical and atypical neuroleptics in rats

Energy Technology Data Exchange (ETDEWEB)

See, R E; Ellison, G; Toga, A W [California Univ., Los Angeles, CA (USA). School of Medicine

1990-01-01

Rats were administered haloperidol, clozapine, raclopride, or no drug for 28 days or 8 months. Following a 3 week withdrawal period, in vitro autoradiography was utilized to examine receptor binding for dopamine D2(({sup 3}H)spiperone and ({sup 3}H)raclopride), dopamine D1(({sup 3}H)SCH23390), GABA{sub A}(({sup 3}H)muscimol), benzodiazepine (({sup 3}H)RO15-1788), and muscarinic ACh receptors (({sup 3}H)QNB). ({sup 3}H)spiperone was elevated in striatal subregions only in haloperidol-treated rats, with the largest increases seen in the 8 month duration animals. Striatal ({sup 3}H)raclopride binding was increased after both short- and long-term treatment in both haloperidol and raclopride, but not clozapine-treated animals. Clozapine-treated rats showed significant increases in ({sup 3}H)SCH23390 in the nucleus accumbens after 28-day administration; otherwise no changes were seen for this ligand in any other groups. Increases in ({sup 3}H)muscimol binding in the substantia nigra reticulata were seen in haloperidol-treated rats after 8 month treatment. Binding of ({sup 3}H)QNB and ({sup 3}H)RO15-1788 were not significantly different from control for any of the drug-treated groups. These data suggest that persisting alterations in receptor binding are primarily seen in dopamine D2 and GABA receptors after withdrawal from chronic administration of haloperidol but not the atypical neuroleptics, clozapine and raclopride. (Authors).

Effect of foot reflexology on pain intensity and duration of labor on primiparous

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Soheila Moghimi Hanjani

2012-12-01

Full Text Available Introduction: The integration of reflexology as one of the non-pharmacological pain relief methods in to midwifery care has become more common in recent years. The aim of this study was to determine the effect of reflexology on pain intensity and the duration of labor in primiparous.Materials and Methods: This clinical trial study was carried out on 80 primiparous women with low risk pregnancy that referring to Karaj hospitals (Iran then randomized in two groups, intervention group which received reflexology for 40 minutes and control group. Severity of labor pain was shown by visual analogue scale (McGill questionnaire, before, half, one and two hours after intervention. Moreover, the duration of labor was determined for both groups.Results: Severity of labor pain before and immediately after intervention foot reflexology did not vary between case and control groups (p>0.05. But half, one and two hours after it, severity of labor pain in the intervention group was lower than the control group (P<0.001. Duration of labor in the intervention group significantly was lower than the control group (P<0.001.Conclusion: Reflexology can lead to decrease in labor pain as well as duration of labor. Therefore, we can use this non-invasive technique to decrease the labor pain and encourage mothers to normal vaginal delivery that is one of the aims of midwifery

Game-based evaluation of personalized support for astronauts in long duration missions

NARCIS (Netherlands)

Smets, N.J.J.M.; Abbing, M.S.; Neerincx, M.A.; Lindenberg, J.; Oostendorp, H. van

2008-01-01

Long duration missions set high requirements for personalized astronaut support that takes into account the social, cognitive and affective state of the astronaut. Such support should be tested as thoroughly as possible before deployment into space. The in-orbit influences of the astronaut's state

Effect of introduction of electronic patient reporting on the duration of ambulance calls.

Science.gov (United States)

Kuisma, Markku; Väyrynen, Taneli; Hiltunen, Tuomas; Porthan, Kari; Aaltonen, Janne

2009-10-01

We examined the effect of the change from paper records to the electronic patient records (EPRs) on ambulance call duration. We retrieved call duration times 6 months before (group 1) and 6 months after (group 2) the introduction of EPR. Subgroup analysis of group 2 was fulfilled depending whether the calls were made during the first or last 3 months after EPR introduction. We analyzed 37 599 ambulance calls (17 950 were in group 1 and 19 649 were in group 2). The median call duration in group 1 was 48 minutes and in group 2 was 49 minutes (P = .008). In group 2, call duration was longer during the first 3 months after EPR introduction. In multiple linear regression analysis, urgency category (P introduction was noticed, reflecting adaptation process to a new way of working.

Training Concept for Long Duration Space Mission

Science.gov (United States)

O'Keefe, William

2008-01-01

There has been papers about maintenance and psychological training for Long Duration Space Mission (LDSM). There are papers on the technology needed for LDSMs. Few are looking at how groundbased pre-mission training and on-board in-transit training must be melded into one training concept that leverages this technology. Even more importantly, fewer are looking at how we can certify crews pre-mission. This certification must ensure, before the crew launches, that they can handle any problem using on-board assets without a large ground support team.

Effect of active warm-up duration on morning short-term maximal ...

African Journals Online (AJOL)

Purpose: To examine the effect of active warm-up duration on short-term maximal performance assessed during Ramadan in the morning. Methods: Twelve healthy active men performed four Wingate tests for measurement of peak power and mean power before and during Ramadan at 09:00 a.m. The tests were performed ...

The Role of Emotion Regulation in Reducing Emotional Distortions of Duration Perception

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Yu Tian

2018-03-01

Full Text Available Emotional events, especially negative ones, are consistently reported to last longer than neutral events. Previous studies suggested that this distortion of duration perception is linked to arousal and attention bias in response to emotional events. Reappraisal and suppression, arguably the most effective strategies for emotion regulation, have been demonstrated to decrease such arousal and attention bias. The present study investigated whether reappraisal and suppression can reduce emotional distortions of duration perception. Seventy-eight Chinese undergraduates were recruited as paid participants and randomly assigned to nonregulation, reappraisal, and suppression groups. Before they performed a temporal bisection task involving presentation of emotional pictures for different durations, the groups were each given one of three different sets of instructions requiring them to passively perceive, reappraise, or suppress the emotions of the pictures. The results indicated that the distortion of duration perception occurred only in the nonregulation group, suggesting that it can be effectively reduced by reappraisal and suppression.

Acute effects of smoking on QT dispersion in healthy males

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Mohammad Ali Akbarzadeh

2014-03-01

Full Text Available 800x600 BACKGROUND: Cigarette smoking increases the risk of ventricular fibrillation and sudden cardiac death (SCD. QT dispersion (QTD is an important predictor of cardiac arrhythmia. The aim of this study was to assess the acute effect of smoking a single standard cigarette containing 1.7 mg nicotine on QT interval and QTD in healthy smokers and nonsmokers. METHODS: The study sample population consisted of 40 healthy male hospital staff, including 20 smokers and 20 nonsmokers. They were asked to refrain from smoking at least 6 h before attending the study. A 12-lead surface electrocardiogram (ECG, recorded at paper speed of 50 mm/s, was obtained from all participants before and 10 min after smoking of a single complete cigarette. QT interval, corrected QT interval, QTD, and corrected QT dispersion (QTcD were measured before and after smoking. RESULTS: Smokers and nonsmokers did not have any significant differences in heart rate (HR (before smoking = 67.35 ± 5.14 vs. 67.70 ± 5.07, after smoking = 76.70 ± 6.50 vs. 76.85 ± 6.50, respectively, QTD (before smoking = 37.75 ± 7.16 vs. 39.15 ± 6.55, after smoking = 44.75 ± 11.97 vs. 45.50 ± 9.58, respectively, and QTcD (before smoking = 39.85 ± 7.40 vs. 41.55 ± 6.57, after smoking = 50.70 ± 14.31 vs. 51.50 ± 11.71, respectively. However, after smoking a single cigarette, HR, mean QTD, and QTcD significantly increased (all had P value <0.001 in comparison to the measures before smoking. CONCLUSION: Smoking of a single complete cigarette in both smokers and nonsmokers results in significant QTD increase, which can cause arrhythmia and SCD.   Keywords: Cardiac, Death, Electrocardiography, Smoking, Sudden  Normal 0 false false false EN-US X-NONE FA MicrosoftInternetExplorer4

Inhibition of radioemesis by disruption of catecholamines in dogs

International Nuclear Information System (INIS)

Luthra, Y.K.; Mattsson, J.L.; Yochmowitz, M.G.

1981-01-01

Dogs were treated 30 min to 1 h before x irradiation with α-methyl-p-tyrosine or 6-hydroxydopamine. A third group of dogs was given a known antiradioemetic drug, haloperidol to verify the sensitivity of the procedure. Irradiated but untreated controls were also used. Light methoxyflurane anesthesia was used for restraint during the exposure. Exposure dose was 800 rad kerma delivered at 50 rad/min to a 10 x 10-cm area covering the abdominal area from xiphoid to pubis. Haloperidol and 6-hydroxydopamine significantly reduced the number of emetic episodes and delayed the onset time to the first episode, α-Methyl-p-tyrosine caused no significant changes. The effectiveness of 6-hydroxydopamine indicates that catecholaminergic neurons are involved in radioemesis, whereas haloperidol and phenothiazine-derivative tranquilizers inhibit radiomesis by blocking catecholamine receptor neurons

QT interval prolongation in users of selective serotonin reuptake inhibitors in an elderly surgical population

DEFF Research Database (Denmark)

van Haelst, Ingrid M M; van Klei, Wilton A; Doodeman, Hieronymus J

2014-01-01

OBJECTIVE: To investigate the association between the use of a selective serotonin reuptake inhibitor (SSRI) and the occurrence of QT interval prolongation in an elderly surgical population. METHOD: A cross-sectional study was conducted among patients (> 60 years) scheduled for outpatient...... preanesthesia evaluation in the period 2007 until 2012. The index group included elderly users of an SSRI. The reference group of nonusers of antidepressants was matched to the index group on sex and year of scheduled surgery (ratio, 1:1). The primary outcome was the occurrence of QT interval prolongation shown...... on electrocardiogram. The QT interval was corrected for heart rate (QTc interval). The secondary outcome was the duration of the QTc interval. The outcomes were adjusted for confounding by using regression techniques. RESULTS: The index and reference groups included 397 users of an SSRI and 397 nonusers, respectively...

A comparison of [/sup 18/F]spiroperidol, [/sup 18/F]benperidol and [/sup 18/F] haloperidol kinetics in baboon brain

International Nuclear Information System (INIS)

Arnett, C.D.; Shiue, C.Y.; Wolf, A.P.; Fowler, J.S.; Logan, J.

1984-01-01

Neuroleptic receptor ligands, spiroperidol, benperidol and haloperidol were labeled with fluorine-18 by a nucleophilic aromatic substitution reaction of p-nitrobenzo-nitrile with /sup 18/F/sup -/ to produce p-[/sup 18/F]fluorobenzonitrile which was converted to p-[/sup 18/F]fluoro-y-chlorobutyrophenone and then alkylated with the appropriate amine to give [/sup 18/F]spiroperidol ([/sup 18/F]SP), [/sup 18/F]benperidol ([/sup 18/F]BEN), or [/sup 18/F]haloperidol ([/sup 18/F]HAL). Specific activity ranged from 3 to 6 Ci/μmol. Anesthetized baboons were injected with 6-17 mCi of [/sup 18/F]-labeled tracer. Kinetic curves (striatum and cerebellum) were obtained from PETT scans up to 4 hr with each drug; [/sup 18/F]SP was studied to 8 hr. [/sup 18/F]SP and [/sup 18/F]BEN exhibited similar kinetics in striatum, with radioactivity concentration plateauing by 30 min after injection and remaining constant for the remainder of the study. These two compounds cleared rapidly from the cerebellum. [/sup 18/F]HAL showed a much different kinetic pattern in the striatum. Although it reached a higher striatal concentration (≅0.07% per ml vs. ≅ 0.02% per ml for [/sup 18/F]SP or [/sup 18/F]BEN), a peak occurred at 30 min after injection, followed by a decline almost as rapid as that in the cerebellum. Plasma analyses for [/sup 18/F]SP showed > 90% unchanged drug up to 5 min and ≅ 30% metabolites at 20 min after injection. Pretreatment with (+)-butaclamol abolished the selective distribution of [/sup 18/F]SP to the striatum in the four animals studied. Both [/sup 18/F]SP and [/sup 18/F]BEN may be suitable for PETT studies of neuroleptic receptors, but the in vivo kinetics of these compounds are markedly different from their in vitro receptor binding kinetics

Acute alteration of cardiac ECG, action potential, I{sub Kr} and the human ether-a-go-go-related gene (hERG) K{sup +} channel by PCB 126 and PCB 77

Energy Technology Data Exchange (ETDEWEB)

Park, Mi-Hyeong; Park, Won Sun; Jo, Su-Hyun, E-mail: suhyunjo@kangwon.ac.kr

2012-07-01

Polychlorinated biphenyls (PCBs) have been known as serious persistent organic pollutants (POPs), causing developmental delays and motor dysfunction. We have investigated the effects of two PCB congeners, 3,3′,4,4′-tetrachlorobiphenyl (PCB 77) and 3,3′,4,4′,5-pentachlorobiphenyl (PCB 126) on ECG, action potential, and the rapidly activating delayed rectifier K{sup +} current (I{sub Kr}) of guinea pigs' hearts, and hERG K{sup +} current expressed in Xenopus oocytes. PCB 126 shortened the corrected QT interval (QTc) of ECG and decreased the action potential duration at 90% (APD{sub 90}), and 50% of repolarization (APD{sub 50}) (P < 0.05) without changing the action potential duration at 20% (APD{sub 20}). PCB 77 decreased APD{sub 20} (P < 0.05) without affecting QTc, APD{sub 90}, and APD{sub 50}. The PCB 126 increased the I{sub Kr} in guinea-pig ventricular myocytes held at 36 °C and hERG K{sup +} current amplitude at the end of the voltage steps in voltage-dependent mode (P < 0.05); however, PCB 77 did not change the hERG K{sup +} current amplitude. The PCB 77 increased the diastolic Ca{sup 2+} and decreased Ca{sup 2+} transient amplitude (P < 0.05), however PCB 126 did not change. The results suggest that PCB 126 shortened the QTc and decreased the APD{sub 90} possibly by increasing I{sub Kr}, while PCB 77 decreased the APD{sub 20} possibly by other modulation related with intracellular Ca{sup 2+}. The present data indicate that the environmental toxicants, PCBs, can acutely affect cardiac electrophysiology including ECG, action potential, intracellular Ca{sup 2+}, and channel activity, resulting in toxic effects on the cardiac function in view of the possible accumulation of the PCBs in human body. -- Highlights: ► PCBs are known as serious environmental pollutants and developmental disruptors. ► PCB 126 shortened QT interval of ECG and action potential duration. ► PCB 126 increased human ether-a-go-go-related K{sup +} current and I{sub Kr}. �

Pulse duration discriminator

International Nuclear Information System (INIS)

Kosakovskij, L.F.

1980-01-01

Basic circuits of a discriminator for discrimination of pulses with the duration greater than the preset one, and of a multifunctional discriminator allowing to discriminate pulses with the duration greater (tsub(p)>tsub(s)) and lesser (tsub(p) tsub(s) and with the duration tsub(p) [ru

Differential Effects of Intermittent versus Continuous Haloperidol Treatment throughout Adolescence on Haloperidol Sensitization and Social Behavior in Adulthood

Science.gov (United States)

Gao, Jun; Li, Ming

2014-01-01

Animal work on the behavioral effects of antipsychotic treatment suggests that different dosing regimens could affect drug sensitivity differently, with an intermittent treatment regimen tending to cause a sensitization effect, while a continuous treatment causing a tolerance. In this study, we explored how haloperidol (HAL) sensitization induced throughout adolescence and tested in adulthood was differentially impacted by these two dosing regimens in the conditioned avoidance response (CAR) test. We also examined how these two dosing regiments affected social interaction and social memory in adulthood. Male adolescent Sprague-Dawley rats were treated with HAL via either osmotic minipump (HAL-0.25 CONT; 0.25 mg/kg/day, n = 14) or daily injection (HAL-0.05 INT; 0.05 mg/kg/injection/day, sc, n = 14), or sterile water (n = 14) from postnatal days (PND) 44 to 71. HAL sensitization was assessed in a challenge test in which all rats were injected with HAL (0.025 and 0.05 mg/kg, sc) on PND 80 and PND 82. Two days later, half of the rats from each group (n = 7/group) were assayed in two 4-trial social interaction tests in which a subject rat was given four 5-min social encounters with a familiar or novel juvenile rat (PND 35–40) at 10 min intervals. Another half were tested in a quinpirole-induced hyperlocomotion assay to assess the potential HAL-induced change in D2-mediated function. Results show that only the intermittent dosing group under the HAL 0.05 mg/kg challenge showed a robust sensitization effect as rats in this group made significantly fewer avoidance responses than those in the vehicle and HAL-0.25 CONT groups. Adolescent HAL treatment did not affect social behavior and social memory, as rats from all 3 groups exhibited a similar level of social interaction and showed a similar level of sensitivity to the change of social stimuli. Similarly, adolescent HAL treatment also did not produce a long-lasting change in D2 function, as all 3 groups exhibited a

Bipolar High-Voltage, Long-Duration Pulsed Radiofrequency Improves Pain Relief in Postherpetic Neuralgia.

Science.gov (United States)

Wan, Cheng-Fu; Liu, Yan; Dong, Dao-Song; Zhao, Lin; Xi, Qi; Yu, Xue; Cui, Wen-Yao; Wang, Qiu-Shi; Song, Tao

2016-07-01

Postherpetic neuralgia (PHN) is often refractory to existing treatments. Treatment of the dorsal root ganglion (DRG) using monopolar pulsed radiofrequency (PRF), which is a non- or minimally neurodestructive technique, is not efficacious in all patients. This study aimed to determine the safety and clinical efficacy of bipolar high-voltage, long-duration PRF on the DRG in PHN patients. Self before-after controlled clinical trial. Department of Pain Medicine, the First Affiliated Hospital of China Medical University. Ninety patients diagnosed with PHN for > 3months were included. Bipolar high-voltage, long-duration PRF at 42°C for 900 seconds was applied after the induction of paresthesias covered the regions of hyperalgesic skin. The therapeutic effects were evaluated using a visual analog scale (VAS) and the 36-item Short Form health survey (SF-36) before treatment and one, 4, 8, and 12 weeks after PRF. The VAS scores at one, 4, 8, and 12 weeks after PRF treatment were significantly lower than before treatment (P DRG is an effective and safe therapeutic alternative for PHN patients. This treatment could improve the quality of life of PHN patients. NO ChiCTR-OCS-14005461.

Eating behavior by sleep duration in the Hispanic Community Health Study/Study of Latinos.

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Mossavar-Rahmani, Yasmin; Jung, Molly; Patel, Sanjay R; Sotres-Alvarez, Daniela; Arens, Raanan; Ramos, Alberto; Redline, Susan; Rock, Cheryl L; Van Horn, Linda

2015-12-01

Sleep is an important pillar of health and a modifiable risk factor for diabetes, stroke and obesity. Little is known of diet and sleep patterns of Hispanics/Latinos in the US. Here we examine eating behavior as a function of sleep duration in a sub-sample of 11,888 participants from the Hispanic Community Health Study/Study of Latinos, a community-based cohort study of Hispanics aged 18-74 years in four US cities. Using a cross-sectional probability sample with self-report data on habitual sleep duration and up to two 24-h dietary recalls, we quantified the Alternative Healthy Eating Index (AHEI-2010) score, a measure of diet quality, and intake of selected nutrients related to cardiovascular health. Linear regression models were fit to estimate least-square means of usual nutrient intake of saturated fats, potassium density, fiber, calcium, caffeine and the AHEI-2010 score by sleep duration adjusting for age, sex, Hispanic/Latino background, income, employment status, education, depressive symptomology, and years lived in the US. Distribution of calories over the day and association with sleep duration and BMI were also examined. Short sleepers (≤6 h) had significantly lower intake of potassium, fiber and calcium and long sleepers (≥9 h) had significantly lower intake of caffeine compared to others sleepers after adjusting for covariates. However no difference in the AHEI-2010 score was seen by sleep duration. Significantly more long sleepers, compared to intermediate and short sleepers, reported having ≥30% total daily calories before bedtime. Not consuming a snack or meal within 3 h before bedtime was associated with higher AHEI-2010 scores. These findings identify novel differences in dietary patterns by sleep duration in a Hispanic/Latino cohort in the U.S. CLINICALTRIALS. NCT02060344. Copyright © 2015 Elsevier Ltd. All rights reserved.

Tp-e interval and Tp-e/QT ratio in patients with celiac disease.

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Demirtaş, K; Yayla, Ç; Yüksel, M; Açar, B; Ünal, S; Ertem, A G; Kaplan, M; Akpinar, M Y; Kiliç, Z M Y; Kayaçetin, E

2017-11-01

Celiac disease is a chronic immune-mediated disease of the small intestine. It has been known that dilated cardiomyopathy and ischemic coronary artery disease have become more frequent in patients with celiac disease. The aim of the study was to assess Tp-e interval and Tp-e/QT ratio in patients with celiac disease. This study was conducted at a single center in collaboration with gastroenterology and cardiology clinics. Between January 2014 and June 2015, a total of 76 consecutive patients were enrolled (38 patients with celiac disease and 38 control subjects). Tp-e interval, Tp-e/QT and Tp-e/QTc ratio were measured from the 12-lead electrocardiogram. Tp-e interval (64.2±11.0 vs. 44.5±6.0; pceliac disease than control subjects. There was a significant positive correlation between Tp-e/QTc ratio and disease duration in patients with celiac disease (r=0.480, p=0.003) and also there was a significant positive correlation between Tp-e/QTc ratio and erythrocyte sedimentation rate (r=0.434, pceliac disease. Whether these changes increase the risk of ventricular arrhythmia deserve further studies. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Intercultural crew issues in long-duration spaceflight

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Kraft, Norbert O.; Lyons, Terence J.; Binder, Heidi

2003-01-01

Before long-duration flights with international crews can be safely undertaken, potential interpersonal difficulties will need to be addressed. Crew performance breakdown has been recognized by the American Institute of Medicine, in scientific literature, and in popular culture. However, few studies of human interaction and performance in confined, isolated environments exist, and the data pertaining to those studies are mostly anecdotal. Many incidents involving crew interpersonal dynamics, those among flight crews, as well as between flight crews and ground controllers, are reported only in non-peer reviewed books and newspapers. Consequently, due to this lack of concrete knowledge, the selection of astronauts and cosmonauts has focused on individual rather than group selection. Additional selection criteria such as interpersonal and communication competence, along with intercultural training, will have a decisive impact on future mission success. Furthermore, industrial psychological research has demonstrated the ability to select a group based on compatibility. With all this in mind, it is essential to conduct further research on heterogeneous, multi-national crews including selection and training for long-duration space missions.

Can we predict the duration of an interglacial?

Directory of Open Access Journals (Sweden)

P. C. Tzedakis

2012-09-01

Full Text Available Differences in the duration of interglacials have long been apparent in palaeoclimate records of the Late and Middle Pleistocene. However, a systematic evaluation of such differences has been hampered by the lack of a metric that can be applied consistently through time and by difficulties in separating the local from the global component in various proxies. This, in turn, means that a theoretical framework with predictive power for interglacial duration has remained elusive. Here we propose that the interval between the terminal oscillation of the bipolar seesaw and three thousand years (kyr before its first major reactivation provides an estimate that approximates the length of the sea-level highstand, a measure of interglacial duration. We apply this concept to interglacials of the last 800 kyr by using a recently-constructed record of interhemispheric variability. The onset of interglacials occurs within 2 kyr of the boreal summer insolation maximum/precession minimum and is consistent with the canonical view of Milankovitch forcing pacing the broad timing of interglacials. Glacial inception always takes place when obliquity is decreasing and never after the obliquity minimum. The phasing of precession and obliquity appears to influence the persistence of interglacial conditions over one or two insolation peaks, leading to shorter (~ 13 kyr and longer (~ 28 kyr interglacials. Glacial inception occurs approximately 10 kyr after peak interglacial conditions in temperature and CO₂, representing a characteristic timescale of interglacial decline. Second-order differences in duration may be a function of stochasticity in the climate system, or small variations in background climate state and the magnitude of feedbacks and mechanisms contributing to glacial inception, and as such, difficult to predict. On the other hand, the broad duration of an interglacial may be determined by the phasing of astronomical parameters and the history of

Effects of Long-Duration Ground Motions on Liquefaction Hazards

Science.gov (United States)

Greenfield, Michael W.

Soil liquefaction during past earthquakes has caused extensive damage to buildings, bridges, dam, pipelines and other elements of infrastructure. Geotechnical engineers use empirical observations from earthquake case histories in conjunction with soil mechanics to predict the behavior of liquefiable soils. However, current empirical databases are insufficient to evaluate the behavior of soils subject to long-duration earthquakes, such as a possible Mw = 9.0 Cascadia Subduction Zone earthquake. The objective of this research is to develop insight into the triggering and effects of liquefaction due to long-duration ground motions and to provide recommendations for analysis and design. Recorded ground motions from 21 case histories with surficial evidence of liquefaction showed marked differences in soil behavior before and after liquefaction was triggered. In some cases, strong shaking continued for several minutes after the soil liquefied, and a variety of behaviors were observed including dilation pulses, continued softening due to soil fabric degradation, and soil stiffening due to pore pressure dissipation and drainage. Supplemental field and laboratory investigations were performed at three sites that liquefied during the 2011 Mw = 9.0 Tohoku earthquake. The recorded ground motions and field investigation data were used in conjunction with laboratory observations, analytical models, and numerical models to evaluate the behavior of liquefiable soils subjected to long-duration ground motions. Observations from the case histories inspired a framework to predict ground deformations based on the differences in soil behavior before and after liquefaction has triggered. This framework decouples the intensity of shaking necessary to trigger liquefaction from the intensity of shaking that drives deformation by identifying the time when liquefaction triggers. The timing-based framework promises to dramatically reduce the uncertainty in deformation estimates compared to

The Effects of Fluvoxamine on the Steady-State Plasma Concentrations of Escitalopram and Desmethylescitalopram in Depressed Japanese Patients.

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Yasui-Furukori, Norio; Tsuchimine, Shoko; Kubo, Kazutoshi; Ishioka, Masamichi; Nakamura, Kazuhiko; Inoue, Yoshimasa

2016-08-01

The aim of this study was to determine the impact of fluvoxamine, an inhibitor of Cytochrome P450 (CYP) 2C19 (CYP2C19), on the pharmacokinetics of escitalopram, a substrate of CYP2C19. Thirteen depressed patients initially received a 20-mg/d dose of escitalopram alone. Subsequently, a 50-mg/d dose of fluvoxamine was administered because of the insufficient efficacy of escitalopram. Plasma concentrations of escitalopram and desmethylescitalopram were quantified using high-performance liquid chromatography before and after fluvoxamine coadministration. The QT and corrected QT (QTc) intervals were measured before and after fluvoxamine coadministration. Fluvoxamine significantly increased the plasma concentrations of escitalopram (72.3 ± 36.9 ng/mL versus 135.2 ± 79.7 ng/mL, P escitalopram were significantly decreased during fluvoxamine coadministration (0.37 ± 0.21 versus 0.21 ± 0.10, P escitalopram. The QTc interval did not change in this condition.

Long-duration transcutaneous electric acupoint stimulation alters small-world brain functional networks.

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Zhang, Yue; Jiang, Yin; Glielmi, Christopher B; Li, Longchuan; Hu, Xiaoping; Wang, Xiaoying; Han, Jisheng; Zhang, Jue; Cui, Cailian; Fang, Jing

2013-09-01

Acupuncture, which is recognized as an alternative and complementary treatment in Western medicine, has long shown efficiencies in chronic pain relief, drug addiction treatment, stroke rehabilitation and other clinical practices. The neural mechanism underlying acupuncture, however, is still unclear. Many studies have focused on the sustained effects of acupuncture on healthy subjects, yet there are very few on the topological organization of functional networks in the whole brain in response to long-duration acupuncture (longer than 20 min). This paper presents a novel study on the effects of long-duration transcutaneous electric acupoint stimulation (TEAS) on the small-world properties of brain functional networks. Functional magnetic resonance imaging was used to construct brain functional networks of 18 healthy subjects (9 males and 9 females) during the resting state. All subjects received both TEAS and minimal TEAS (MTEAS) and were scanned before and after each stimulation. An altered functional network was found with lower local efficiency and no significant change in global efficiency for healthy subjects after TEAS, while no significant difference was observed after MTEAS. The experiments also showed that the nodal efficiencies in several paralimbic/limbic regions were altered by TEAS, and those in middle frontal gyrus and other regions by MTEAS. To remove the psychological effects and the baseline, we compared the difference between diffTEAS (difference between after and before TEAS) and diffMTEAS (difference between after and before MTEAS). The results showed that the local efficiency was decreased and that the nodal efficiencies in frontal gyrus, orbitofrontal cortex, anterior cingulate gyrus and hippocampus gyrus were changed. Based on those observations, we conclude that long-duration TEAS may modulate the short-range connections of brain functional networks and also the limbic system. Copyright © 2013 Elsevier Inc. All rights reserved.

Relationship between Corrected-QT Intervals and Other ECG Characteristics with Methadone Dose in Methadone Maintenance Treatment (MMT Patients and Healthy Subjects: A Case- Control Study

Directory of Open Access Journals (Sweden)

Mina Akbari Rad

2017-05-01

Full Text Available Background In this study we assessed the relationship between corrected-QT intervals and other ECG characteristics with methadone dose and other parameters in MMT patients and healthy subjects. Methods This was a case-control study which was carried out on patients underwent MMT and healthy control group who had been referred to Ebne-Sina academic hospital, Mashhad during 2014 - 2015. At the time of the study, 40 patients who received MMT therapy for at least 6 months and 40 voluntary healthy subjects who matched on age and sex enrolled in the study. 12-lead ECG was performed for all the patients. Mean QT interval, PR interval and QRS duration in every 12 leads were documented for each patient in maximum. Results To evaluate the patients, we divided 80 patients into two groups: 40 patients under treatment with Methadone and 40 voluntary participants as control group. There were 20 males and 20 females in each group. Duration of addiction was 214.80 ± 126.99 months in MMT group. Significant differences were observed in PRi between the patient and control groups (P = 0.007, and also between methadone dose and PRi (r = 0.468, P = 0.038 in males. QTc prolongation was reported in 4 patients of addicted group (10%. All of the QTc prolongation patients were female (P = 0.037. There was significant relationship between PRi and weight (P = 0.015, addiction period (P = 0.011, methadone treatment period (P = 0.018 as well as methadone dosage (P = 0.14. Methadone cut off point of 65 mg had a significant relationship with systolic blood pressure (P = 0.002, diastolic blood pressure (P = 0.013, QTCi (P = 0.016 and QRS (P = 0.044; however, no significant relationship was reported with PRi (P = 0.451. Conclusions We found that there is no exact dosage of methadone in which the side effects such as TdP (Torsade de pointes or QTc prolongation can be predicted. Female gender and methadone dosage ≥ 65 mg were risk factors of our study for QTc prolongation which

Breastfeeding Duration and Primary Reasons for Breastfeeding Cessation among Women with Postpartum Depressive Symptoms.

Science.gov (United States)

Bascom, Erin McElderry; Napolitano, Melissa A

2016-05-01

Although postpartum depression is associated with lower breastfeeding initiation rates and shorter breastfeeding duration, the potential mechanisms through which this relationship functions are not well understood. This study examined the breastfeeding behaviors of women with postpartum depressive symptoms (PDS) to identify potential motivations for early breastfeeding cessation. An analysis of quantitative data from the Infant Feeding Practices Study II examined the relationship between PDS and breastfeeding behaviors, including breastfeeding duration and primary reasons for early breastfeeding cessation. Of the women in the sample, 30.9% met criteria for mild PDS. Women with PDS had shorter overall (18.4 vs 21.8 weeks, P = .001) and exclusive breastfeeding duration (3.6 vs 4.7 weeks, P = .012) than women without PDS. A larger proportion of women with PDS stopped breastfeeding before 6 months (68.7% vs 57.2%, P household duties" (OR = 1.90, P = .011) as a primary reason for breastfeeding cessation among women who stopped breastfeeding before 6 months. After controlling for these same covariates, women with PDS had, on average, 2.4 weeks shorter breastfeeding duration than women without PDS (P = .025). There is a high prevalence of depressive symptoms among new mothers, and most do not breastfeed for recommended time periods. Increased PDS screening during prenatal and postpartum visits and promotion of lactation support services may better address the high rates of PDS and suboptimal breastfeeding behavior. © The Author(s) 2015.

Effect Observation of Haloperidol Combined with Psychological Behavioral Therapy in Treatment of Children with Tic Disorders%氟哌啶醇结合心理行为疗法治疗儿童抽动障碍疗效观察

Institute of Scientific and Technical Information of China (English)

陈宇; 钟燕; 丁大为; 游诚; 何毅

2016-01-01

Objective To investigate the clinical effects of haloperidol combined with psychological behavioral therapy in the treatment of children with tic disorders (TD). Methods 70 children with tic disorders treated in our hospital from January 2013 to December 2014 were selected and randomly divided into observation group and control group, with 35 cases in each group. The control group was given conventional haloperidol therapy, the observation group was given haloperidol combined with psychological behavioral therapy. The clinical efficacy was evaluated by Tic evaluation questionnaire. Results After the treatment, the Tic questionnaire scores of vocal tic, motor tic, behavior, motor restlessness in two groups increased significantly, and the scores of observation group were significantly lower than those of control group, with statistically significant difference (P <0.05). The total effective rate of observation group was 97.14%, significantly higher than 80.00%of control group, with statistical ly significant difference (P <0.05). Conclusions Haloperidol combined with psychological behavioral therapy can significantly improve the tic symptoms of children, and has better curative effects than conventional haloperidol therapy.%目的：探讨氟哌啶醇结合心理行为疗法治疗儿童抽动障碍的疗效。方法将2013年1月至2014年12月来我院诊治的70例儿童抽动障碍患者随机分成观察组和对照组，每组各35例。对照组采用常规氟哌啶醇治疗，观察组采取氟哌啶醇结合心理行为疗法治疗。使用抽动问卷评价临床疗效差异。结果两组治疗后抽动问卷调查各因子（发声性抽动、运动性抽动、行为、运动不宁)评分较治疗前均显著降低，且观察组治疗后抽动问卷各因子评分显著低于对照组，差异均具有统计学意义（P<0.05)。观察组治疗后临床总有效率为97.14％，明显高于对照组的80.0％，差异具有统计学意义（P<0.05)�

Laser-driven short-duration heating angioplasty: dilatation performance in cadaver atherosclerotic femoral arteries

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Shimazaki, Natsumi; Naruse, Sho; Arai, Tsunenori; Imanishi, Nobuaki; Aiso, Sadakazu

2013-03-01

The purpose of this study was to investigate the artery dilatation performance of the short-duration heating balloon catheter in cadaver stenotic arteries. We designed a prototype short-duration heating balloon catheter that can heat artery media to around 60 °C in 15-25 s by a combination of laser-driven heat generation and continuous fluid irrigation in the balloon. We performed ex vivo short-duration heating dilatation in the cadaver atherosclerotic femoral arteries (initial percent diameter stenosis was 36-98%), with the maximum balloon temperature of 65+/-5 °C, laser irradiation duration of 25 s, and balloon dilatation pressure of 3.5 atm. The artery lumen configurations before and after the dilatations were assessed with a commercial IVUS system. After the short-duration heating dilatations, the percent diameter stenosis was reduced below 30% without any artery tears or dissections. We estimated that the artery media temperature was raised to around 60 °C in which plaque thickness was below 0.8 mm by a thermal conduction calculation. The estimated maximum temperature in artery adventitia and surrounding tissue was up to 45 °C. We found that the short-duration heating balloon could sufficiently dilate the cadaver stenotic arteries, without thermal injury in artery adventitia and surroundings.

The optimal time of discontinuing methimazole before radioiodine therapy

International Nuclear Information System (INIS)

Moosavi, Z.; Zakavi, R.

2001-01-01

Hyperthyroidism is a common disease and one of the best methods for its treatment is radioiodine therapy with Treatment with antithyroid drugs brings patients to euthyroidism before radioiodine therapy. Antithyroid drugs should be discontinued before radioiodine therapy to increase thyroid uptake. The purpose of this study was to determine the optimal time of methimazole discontinuation. One hundred eighty four patients, who were referred for radioiodine therapy were classified in 3 groups according to the duration of methimazole discontinuation before thyroid uptake (RAIU) measurement. Group 1,2 and 3 were patients who discontinued methimazole (48-72 h rs), (72-120 h rs) and more than 120 h rs before RAIU measurement, respectively. Mean thyroid uptake in group 1, 2 and 3 was (64±151.1%), (60.1±14.1%) and (59.3±12.8), respectively. No significant difference was noted in thyroid uptake between these groups (F= 1.83, P<0.16). This study shows that 48-72 h rs of methimazole discontinuation before radioiodine therapy is enough and longer term abstention is not associated with higher uptake

New age- and sex-specific criteria for QT prolongation based on rate correction formulas that minimize bias at the upper normal limits.

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Rautaharju, Pentti M; Mason, Jay W; Akiyama, Toshio

2014-07-01

Existing formulas for rate-corrected QT (QTc) commonly fail to properly adjust the upper normal limits which are more critical than the mean QTc for evaluation of prolonged QT. Age- and sex-related differences in QTc are also often overlooked. Our goal was to establish criteria for prolonged QTc using formulas that minimize QTc bias at the upper normal limits. Strict criteria were used in selecting a study group of 57,595 persons aged 5 to 89 years (54% women) and to exclude electrocardiograms (ECG) with possible disease-associated changes. Two QT rate adjustment formulas were identified which both minimized rate-dependency in the 98 th percentile limits: QTcmod, based on an electrophysiological model (QTcMod = QTx(120 + HR)/180)), and QTcLogLin, a power function of the RR interval with exponents 0.37 for men and 0.38 for women. QTc shortened in men during adolescence and QTcMod became 13 ms shorter than in women at age 20-29 years. The sex difference was maintained through adulthood although decreasing with age. The criteria established for prolonged QTc were: Age < 40 years, men 430 ms, women 440 ms; Age 40 to 69, men 440 ms, women 450 ms; Age ≥ 70 years, men 455 ms, and women 460 ms. Sex difference in QTc originates from shortened QT in adolescent males. Upper normal limits for QTc vary substantially by age and sex, and it is essential to use age- and sex-specific criteria for evaluation of QT prolongation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The effect of sertindole on QTD and TPTE

DEFF Research Database (Denmark)

Nielsen, J; Andersen, M P; Graff, Claus

2010-01-01

Recent research suggests that other surrogate markers than QTc, including QTc dispersion and Tpeak-Tend, may better correlate with cardiac arrhythmia risk. While sertindole significantly prolongs the QTc interval, the effects on other markers of arrhythmia risk, such as QTc dispersion and Tpeak-T...

Effects of Short- and Long-Duration Space Flight on Neuromuscular Function

Science.gov (United States)

Buxton, Roxanne E.; Spiering, Barry A.; Ryder, Jeffrey W.; Ploutz-Snyder, Lori L.; Bloomberg, Jacob J.

2010-01-01

The Functional Task Tests (FTT) is an interdisciplinary study designed to correlate the changes in functional tasks (such as emergency egress, ladder climbing, and hatch opening) with changes in neuromuscular, cardiovascular, and sensorimotor function. One aspect of the FTT, the neuromuscular function test, is used to investigate the neuromuscular component underlying changes in the ability of astronauts to perform functional tasks (representative of critical mission tasks) safely and quickly after flight. PURPOSE: To describe neuromuscular function after short- and long-duration space flight. METHODS: To date, 5 crewmembers on short-duration (10- to 15-day) missions and 3 on long-duration missions have participated. Crewmembers were assessed 30 days before flight, on landing day (short-duration subjects only) and 1, 6, and 30 days after landing. The interpolated twitch technique, which utilizes a combination of maximal voluntary contractions and electrically evoked contractions, was used to assess the maximal voluntary isometric force (MIF) and central activation capacity of the knee extensors. Leg-press and bench-press devices were used to assess MIF and maximal dynamic power of the lower and upper body respectively. Specifically, power was measured during concentric-only ballistic throws of the leg-press sled and bench-press bar loaded to 40% and 30% of MIF respectively. RESULTS: Data are currently being collected from both Shuttle and ISS crewmembers. Emerging data indicate that measures of knee extensor muscle function are decreased with long-duration flight. DISCUSSION: The relationships between flight duration, neural drive, and muscle performance are of particular interest. Ongoing research will add to the current sample size and will focus on defining changes in muscle performance measures after long-duration space flight.

Different effects of long-term haloperidol administration on GABA/sub A/ and benzodiazepine receptors in various parts of the brain

International Nuclear Information System (INIS)

Vasar, Oe.Oe.; Nurk, A.M.; Maimets, M.O.; Soosaar, A.H.; Allikmets, L.H.

1986-01-01

The data described in this paper are evidence that long-term administration of haloperidol has an opposite effect on the density of GABA/sub A/ and benzodiazepine receptors in the fore- and hindbrain. These changes are reflected at the molecular level as reversal of behavioral effect of the GABA/sub A/ agonist muscimol and the benzodiazepine agonist Ro15-1788. By means of parallel behavioral tests, binding of 3 H-muscimol in the fore- and hindbrain of rats was investigated in experiments in vitro. 3 H-flunitrazepam binding experiments were carried out in vivo on mice. Parallel with reversal of the behavioral effects of muscimol and Ro15-1788, the number of binding sites both for 3 H-muscimol and for 3 H-flunitrazepam in the forebrain was reduced; in the hindbrain the opposite process took place

Assessment of cabozantinib treatment on QT interval in a phase 3 study in medullary thyroid cancer: evaluation of indirect QT effects mediated through treatment-induced changes in serum electrolytes.

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Miles, Dale R; Lacy, Steven A; Wada, David R; Milwee, Steve; Yaron, Yifah; Nguyen, Linh T

2017-08-01

This study evaluated factors impacting QTc interval in a phase 3 trial of cabozantinib in progressive, metastatic, medullary thyroid cancer (MTC). Electrocardiogram (12-lead ECG) measurements were obtained at screening, and at pre-dose, and 2, 4, and 6 h post-dose on Days 1 and 29 in a phase 3 study in patients with MTC treated with cabozantinib (140 mg/day). Central tendency analyses were conducted on baseline-corrected QTc values. Linear and nonlinear mixed-effects models were used to evaluate potential factors affecting the QTc interval, including serum electrolytes, patient demographics, and cabozantinib concentration. Central tendency analysis showed that oral cabozantinib (140 mg/day) produced a 10-15 ms increase in delta-delta Fridericia corrected QT (∆∆QTcF) and delta-delta study-specific corrected QT (∆∆QTcS) on Day 29, but not on Day 1. Further analysis showed that QTcS provided a slightly more accurate QT correction than QTcF. Mixed-effects models evaluating serum electrolytes, age, sex, and cabozantinib concentration showed that decreased serum calcium and potassium could explain the majority of cabozantinib treatment-associated QTcS prolongation observed in this study. Cabozantinib treatment prolongs the ∆∆QTcF interval by 10-15 ms. There was the absence of a strong relationship between cabozantinib concentration and QTcS prolongation. Cabozantinib treatment effects on serum calcium and potassium best explain the QTcS prolongation observed in this study.

Discounted Duration Calculus

DEFF Research Database (Denmark)

Ody, Heinrich; Fränzle, Martin; Hansen, Michael Reichhardt

2016-01-01

To formally reason about the temporal quality of systems discounting was introduced to CTL and LTL. However, these logic are discrete and they cannot express duration properties. In this work we introduce discounting for a variant of Duration Calculus. We prove decidability of model checking...... for a useful fragment of discounted Duration Calculus formulas on timed automata under mild assumptions. Further, we provide an extensive example to show the usefulness of the fragment....

Does increasing active warm-up duration affect afternoon short-term maximal performance during Ramadan?

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Baklouti, Hana; Aloui, Asma; Chtourou, Hamdi; Briki, Walid; Chaouachi, Anis; Souissi, Nizar

2015-01-01

The purpose of this study was to examine the effect of active warm-up duration on short-term maximal performance assessed during Ramadan in the afternoon. Twelve healthy active men took part in the study. The experimental design consisted of four test sessions conducted at 5 p.m., before and during Ramadan, either with a 5-minute or a 15-minute warm-up. The warm-up consisted in pedaling at 50% of the power output obtained at the last stage of a submaximal multistage cycling test. During each session, the subjects performed two vertical jump tests (squat jump and counter movement jump) for measurement of vertical jump height followed by a 30-second Wingate test for measurement of peak and mean power. Oral temperature was recorded at rest and after warming-up. Moreover, ratings of perceived exertion were obtained immediately after the Wingate test. Oral temperature was higher before Ramadan than during Ramadan at rest, and was higher after the 15-minute warm-up than the 5-minute warm-up both before and during Ramadan. In addition, vertical jump heights were not significantly different between the two warm-up conditions before and during Ramadan, and were lower during Ramadan than before Ramadan after both warm-up conditions. Peak and mean power were not significantly different between the two warm-up durations before Ramadan, but were significantly higher after the 5-minute warm-up than the 15-minute warm-up during Ramadan. Moreover, peak and mean power were lower during Ramadan than before Ramadan after both warm-up conditions. Furthermore, ratings of perceived exertion were higher after the 15-minute warm-up than the 5-minute warm-up only during Ramadan. The prolonged active warm-up has no effect on vertical jump height but impairs anaerobic power assessed during Ramadan in the afternoon.

Shorter epilepsy duration is associated with better seizure outcome in temporal lobe epilepsy surgery

Directory of Open Access Journals (Sweden)

Lucas Crociati Meguins

2015-03-01

Full Text Available Objective To investigate the influence of patient’s age and seizure onset on surgical outcome of temporal lobe epilepsy (TLE. Method A retrospective observational investigation performed from a cohort of patients from 2000 to 2012. Results A total of 229 patients were included. One-hundred and eleven of 179 patients (62% were classified as Engel I in the group with < 50 years old, whereas 33 of 50 (66% in the group with ≥ 50 years old group (p = 0.82. From those Engel I, 88 (61% reported epilepsy duration inferior to 10 years and 56 (39% superior to 10 years (p < 0.01. From the total of patients not seizure free, 36 (42% reported epilepsy duration inferior to 10 years and 49 (58% superior to 10 years (p < 0.01. Conclusion Patients with shorter duration of epilepsy before surgery had better postoperative seizure control than patients with longer duration of seizures.

Factors predicting the duration of adrenal insufficiency in patients successfully treated for Cushing disease and nonmalignant primary adrenal Cushing syndrome.

Science.gov (United States)

Prete, Alessandro; Paragliola, Rosa Maria; Bottiglieri, Filomena; Rota, Carlo Antonio; Pontecorvi, Alfredo; Salvatori, Roberto; Corsello, Salvatore Maria

2017-03-01

Successful treatment of Cushing syndrome causes transient or permanent adrenal insufficiency deriving from endogenous hypercortisolism-induced hypothalamus-pituitary-adrenal-axis suppression. We analyzed pre-treatment factors potentially affecting the duration of adrenal insufficiency. We conducted a retrospective analysis on patients successfully treated for Cushing disease (15 patients) who underwent transsphenoidal surgery, and nonmalignant primary adrenal Cushing syndrome (31 patients) who underwent unilateral adrenalectomy, divided into patients with overt primary adrenal Cushing syndrome (14 patients) and subclinical primary adrenal Cushing syndrome (17 patients). Epidemiological data, medical history, and hormonal parameters depending on the etiology of hypercortisolism were collected and compared to the duration of adrenal insufficiency. The median duration of follow-up after surgery for Cushing disease and primary adrenal Cushing syndrome was 70 and 48 months, respectively. In the Cushing disease group, the median duration of adrenal insufficiency after transsphenoidal surgery was 15 months: younger age at diagnosis and longer duration of signs and symptoms of hypercortisolism before diagnosis and surgery were associated with longer duration of adrenal insufficiency. The median duration of adrenal insufficiency was 6 months for subclinical primary adrenal Cushing syndrome and 18.5 months for overt primary adrenal Cushing syndrome. The biochemical severity of hypercortisolism, the grade of hypothalamus-pituitary-adrenal-axis suppression, and treatment with ketoconazole before surgery accounted for longer duration of adrenal insufficiency. In patients with Cushing disease, younger age and delayed diagnosis and treatment predict longer need for glucocorticoid replacement therapy after successful transsphenoidal surgery. In patients with primary adrenal Cushing syndrome, the severity of hypercortisolism plays a primary role in influencing the duration of

Optimal antidepressant dosing. Practical framework for selection, titration, and duration of therapy.

Science.gov (United States)

Nielsen, J W; Witek, M W; Hurwitz, S

2000-10-01

Appropriate antidepressant dosing and trial duration are crucial for successful treatment of depression. Before prescribing an antidepressant, primary care physicians should take into account each patient's history, responses to previous antidepressants, depressive symptoms, coexisting illnesses, and current prescriptions. Physicians must be able to help patients manage side effects and know when to discontinue treatment, switch antidepressants, or refer patients to a psychiatrist.

Utility of heart rate turbulence and T-Wave alternans to assess risk for Re-admission and cardiac death in hospitalized heart failure patients.

Science.gov (United States)

Yamada, Shinya; Yoshihisa, Akiomi; Sato, Yu; Sato, Takamasa; Kamioka, Masashi; Kaneshiro, Takashi; Oikawa, Masayoshi; Kobayashi, Atsushi; Suzuki, Hitoshi; Ishida, Takafumi; Takeishi, Yasuchika