WorldWideScience

Sample records for buspirone

  1. Compound list: buspirone [Open TG-GATEs

    Lifescience Database Archive (English)

    Full Text Available buspirone BPR 00173 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro.../buspirone.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/buspirone.Rat.in_vitro.Liver.zip ...

  2. Pharmacokinetics of buspirone in autistic children.

    Science.gov (United States)

    Edwards, David J; Chugani, Diane C; Chugani, Harry T; Chehab, Jamal; Malian, Monica; Aranda, Jacob V

    2006-05-01

    Buspirone is used to treat generalized anxiety disorder in children and may be useful in developmental disorders in which brain serotonin synthesis is altered. Autistic children (13 boys, 7 girls) were given a single oral dose of 2.5 mg (2-3 years) or 5.0 mg (4-6 years). Blood was collected for 8 hours, and plasma was assayed for buspirone and its metabolite 1-pyrimidinylpiperazine (1-PP). The peak concentration of buspirone averaged 1141 +/- 748 pg/mL with a time to maximum concentration of 0.8 hours. Half-life was 1.6 +/- 0.3 hours. Peak concentrations of 1-PP were 4.5-fold higher than for buspirone. Girls had higher peak concentrations (1876 vs 746 pg/mL) for buspirone and a lower peak 1-PP/buspirone concentration ratio. These results suggest that buspirone is rapidly absorbed and eliminated in young children with extensive metabolism to 1-PP. Plasma concentrations with 2.5- to 5.0-mg doses were similar to those observed in older children receiving 7.5- to 15-mg doses.

  3. [Buspirone in the treatment of cerebellar ataxia].

    Science.gov (United States)

    Svetel, M; Vojvodić, N; Filipović, S R; Dragasević, N; Sternić, N; Kostić, V S

    1999-01-01

    Ataxia is defined as a disturbance which, quite independent of any motor weakness, alters direction and extent of voluntary movement and impairs the sustained voluntary of reflex muscle contraction necessary for maintaining postiue and equilibrium [1]. Since pathophysiological basis of cerebeller ataxia is still not completely clear, the current therapeutic attempts are mainly symptom-oriented [3]. One possible approach could be a modification of potentially involved neurotransmitter systems of the cerebellum, where particularly interesting is the serotonergic system. However, attempts with levorotatory form of tryptophan (5-HT precursors) proved to be ineffective [4, 5]. Since receptors in the cerebellum are mainly of 5-HTIA subtype, the use of specific agonists might be a more reasonable therapy [6]. The study initially involved 11 patients, but only 9 completed the protocol due to unfavorable side effects. Our open label prospective study lasted for 15 weeks. The patients were tested before the beginning of the treatment (initial visit), at 7th (first visit) and 11th week (second visit) of continuous therapy, and eventually at 15th week (final visit). The daily dose was 40 mg at the first and 60 mg at the second visit. We used the evaluation scale gurposed for cerebellar functions testing (speech, gait, coordination and ocular movements). Significant improvement of cerebellar ataxia in patients under buspiron therapy has been noted. We analyzed the results obtained from our 9 patients (4 females and 5 males), of which 6 patients suffered from cerebellar degeneration, one from multiple sclerosis, one from Ramsey-Hunt syndrome, and one from pontine myelinolysis. At the initial visit the patient score was 18.9 (SD = 7.3), subsequently, at the iirst visit the score was 15.4 (SD = 8), while the second visit yielded the score of 12.9 (SD = 8.2), and finally, after a two-weeks lasting wash-out period, it was 17.7 (SD = 7.1) (Table 1). It was found that patients

  4. Buspirone versus Methylphenidate in the Treatment of Attention Deficit Hyperactivity Disorder: A Double-Blind and Randomized Trial

    Science.gov (United States)

    Davari-Ashtiani, Rozita; Shahrbabaki, Mahin Eslami; Razjouyan, Katayoon; Amini, Homayoun; Mazhabdar, Homa

    2010-01-01

    The efficacy and side effects of buspirone compared with methylphenidate (MPH) in the treatment of children with attention-deficit/hyperactivity disorder (ADHD). A total of 34 children with ADHD as defined by DSM-IV-TR were randomized to buspirone or methylphenidate dosed on weight-adjusted basis at buspirone (0.5 mg/kg/day) and methylphenidate…

  5. Monoaminergic involvement in the pharmacological actions of buspirone.

    OpenAIRE

    Skolnick, P; Weissman, B. A.; Youdim, M. B.

    1985-01-01

    Buspirone, MJ-13805 and MJ-13653 did not produce a '5-hydroxytryptamine (5-HT) syndrome' in rats at doses up to 20 mg kg-1. These drugs were very weak 5-HT uptake blockers (IC50 much greater than 10 microM) compared to drugs such as chlorimipramine. These drugs did not inhibit either monoamine oxidase (MAO)-A or MAO-B. The Ki values for these agents as inhibitors of [3H]-5-HT and [3H]-ketanserin binding to rat frontal cortex or hippocampal membranes were in the microM range, well above the br...

  6. Evaluation of Buspirone on Streptozotocin Induced Type 1 Diabetes and Its Associated Complications

    Directory of Open Access Journals (Sweden)

    Suchi Raghunathan

    2014-01-01

    Full Text Available We have evaluated the effect of buspirone (1.5 mg/kg/day, p.o. type 1 diabetes induced cardiovascular complications induced by streptozotocin (STZ, 45 mg/kg, i.v. in Wistar rats. Various biochemical, cardiovascular, and hemodynamic parameters were measured at the end of 8 weeks of treatment. STZ produced significant hyperglycaemia, hypoinsulinemia, and dyslipidemia, which was prevented by buspirone treatment. STZ produced increase in serum creatinine, urea, lactate dehydrogenase, creatinine kinase, and C-reactive protein levels and treatment with buspirone produced reduction in these levels. STZ produced increase in cardiac and LV hypertrophy index, LV/RV ratio, and LV collagen, which were decreased by buspirone treatment. Buspirone also prevented STZ induced hemodynamic alterations and oxidative stress. These results were further supported by histopathological studies in which buspirone showed marked reduction in fibrosis and cardiac fiber disarray. In conclusion, our data suggests that buspirone is beneficial as an antidiabetic agent in type 1 diabetes mellitus and also prevents its cardiac complications.

  7. Buspirone reduces sexual risk-taking intent but not cocaine self-administration.

    Science.gov (United States)

    Bolin, B Levi; Lile, Joshua A; Marks, Katherine R; Beckmann, Joshua S; Rush, Craig R; Stoops, William W

    2016-06-01

    Impulsive sexual decision-making may underlie sexual risk-taking behavior that contributes to the disproportionately high prevalence of HIV infection among cocaine users. Delay-discounting procedures measure impulsive decision-making and may provide insight into the underlying mechanisms of sexual risk-taking behavior. The anxiolytic drug buspirone reduces delay discounting in rats and blunts the reinforcing effects of cocaine in some preclinical studies suggesting that it might have utility in the treatment of cocaine-use disorders. This study determined whether buspirone mitigates impulsive risky sexual decision-making in cocaine users on a sexual delay-discounting procedure. The effects of buspirone maintenance on the abuse-related and physiological effects of cocaine were also tested. Nine (N = 9) current cocaine users completed a repeated-measures, inpatient protocol in which sexual delay discounting was assessed after 3 days of maintenance on placebo and buspirone (30 mg/day) in counterbalanced order. The reinforcing, subject-rated, and physiological effects of placebo and intranasal cocaine (15 and 45 mg) were also assessed during buspirone and placebo maintenance. Buspirone increased the likelihood of condom use for hypothetical sexual partners that were categorized as most likely to have a sexually transmitted infection and least sexually desirable. Cocaine functioned as a reinforcer and increased positive subjective effects ratings, but buspirone maintenance did not impact these effects of cocaine. Buspirone was also safe and tolerable when combined with cocaine and may have blunted some its cardiovascular effects. The results from the sexual delay-discounting procedure indicate that buspirone may reduce preference for riskier sex in cocaine users. (PsycINFO Database Record PMID:27254258

  8. Development and optimization of buspirone oral osmotic pump tablet.

    Science.gov (United States)

    Derakhshandeh, K; Berenji, M Ghasemnejad

    2014-01-01

    The aim of the current study was to design a porous osmotic pump-based drug delivery system for controlling the release of buspirone from the delivery system. The osmotic pump was successfully developed using symmetric membrane coating. The core of the tablets was prepared by direct compression technique and coated using dip-coating technique. Drug release from the osmotic system was studied using USP paddle type apparatus. The effect of various processing variables such as the amount of osmotic agent, the amount of swellable polymer, concentration of the core former, concentration of the plasticizer, membrane thickness, quantum of orifice on drug release from osmotic pump were evaluated. Different kinetic models (zero order, first order and Higuchi model) were applied to drug release data in order to establish the kinetics of drug release. It was found that the drug release was mostly affected by the amount of NaCl as osmotic agent, the swellable polymer; hydroxy propyl methyl cellulose (HPMC), the amount of PEG-400 and cellulose acetate in the coating solution and thickness of the semipermeable membrane. The optimized formulation released buspirone independent of pH and orifice quantum at the osmogen amount of 42%, hydrophilic polymer of 13% and pore size of 0.8 mm on the tablet surface. The drug release of osmotic formulation during 24 h showed zero order kinetics and could be suggested that this formulation as a once-daily regimen improves pharmacokinetic parameters of the drug and enhances patient compliance. PMID:25657794

  9. A Comparison of Risperidone and Buspirone for Treatment of Behavior Disorders in Children with Phenylketonuria

    OpenAIRE

    FAYYAZI, Afshin; Elham SALARI*; Ali KHAJEH; Abdi GAJARPOUR

    2014-01-01

    How to Cite This Article: Fayyazi A, Salari E, Khajeh A, Ghajarpour A. A Comparison of Risperidone and Buspirone for Treatment ofBehavior Disorders in Children with Phenylketonuria. Iran J Child Neurol. 2014 Autumn; 8(4):33-38.AbstractObjectiveMany patients with late-diagnosed phenylketonuria (PKU) suffer from severe behavior problems. This study compares the effects of buspirone and risperidone on reducing behavior disorders in these patients.Materials & MethodsIn this crossover clinical...

  10. Effect of ashwagandha and aloe vera pretreatment on intestinal transport of buspirone across rat intestine

    OpenAIRE

    Yamsani, Shravan K.; Devandla, Adukondalu; Yamsani, Vamshi V.; Athukuri, Bhargavilatha; Gannu, Ramesh; Palem, Chinna R.; Rao, Yamsani Madhusudan; Manda, Sarangapani

    2011-01-01

    The transport of buspirone across rat intestine (duodenum, jejunum, ileum and colon) was studied by using the non-everted sac method. Rats were pretreated with ashwagandha (Withania somnifera) and Aloe vera juice for 7 days. The rats were sacrificed by using anesthetic ether, the intestinal segments were isolated and used for the studies. The probe drug (buspirone) solution was placed in the isolated intestinal sac. Samples were collected at preset time points and replaced with fresh buffer. ...

  11. Pharmacokinetics of a prototype formulation of sublingual testosterone and a buspirone tablet, versus an advanced combination tablet of testosterone and buspirone in healthy premenopausal women

    NARCIS (Netherlands)

    van Rooij, Kim; de Leede, Leo; Frijlink, Henderik W; Bloemers, Jos; Poels, Saskia; Koppeschaar, Hans; Olivier, Berend; Tuiten, Adriaan

    2014-01-01

    The study aimed to compare the kinetics of two novel combination drug products for Female Sexual Interest/Arousal Disorder (FSIAD). Thirteen women received testosterone via the sublingual route followed 2.5 hours later by a buspirone tablet, versus a single combination tablet swallowed at once. The

  12. Effect of pomegranate pretreatment on the oral bioavailability of buspirone in male albino rabbits

    OpenAIRE

    M. Sarangapani; Y Madhusudan Rao; R Shiva Kumar; Ramesh, G.; Y Vamshi Vishnu; Bhargavi Latha, A.; Adukondalu, D.; Y Shravan Kumar

    2011-01-01

    Background and the Purpose of the study: Many drug substances and variety of naturally occurring dietary or herbal components are capable of interaction with the CYP enzyme system. The aim of the study was to investigate the effect of pomegranate juice pretreatment on the bioavailability of buspirone in rabbits. Methods: White New Zealand rabbits weighing 2.1±0.13 Kg were selected for study. The bioavailability of buspirone after pre-treatment with pomegranate juice (10 ml Kg-1 for sev...

  13. Pharmacokinetics study of extended release formulations of buspirone hydrochloride in Beagle dogs

    Institute of Scientific and Technical Information of China (English)

    CUI Meng-cun; LI Jing-lai; CHEN Yan; WANG Xiao-ying; QIAO Jian-zhong; ZHANG Zhen-qing; RUAN Jin-xiu

    2008-01-01

    Objective To evaluate the pharmacokinetics (PK) properties of extended release formulations of buspirone hydrochloride in Beagle dogs. Methods A randomized, two period, two treatment, two sequence crossover bioequivalenee study was designed; six healthy Beagle dogs were randomly divided into two groups, each group was orally given buspirone tablets or buspirone extended capsule containing 15 mg buspirone hydrochloride. Blood samples (about 1 mL) were collected in heparinized tubes before dosing and at 0.33, 0.67, 1,2, 3, 4, 6, 8, 10, 12, 18, 24 h after administration, and were then immediately centrifuged at 3000 rpm for 15 min. The pharmacokinetics (PK) properties of the drugs were evaluated using the liquid chromatographic-tandem mass spectrometric (LC-MS/MS) method. Results The mean tmax was 4.7, 0.8 h and Cmax values was 1.8, 6.9 μg·L-1, respectively for the sustained-release test (capsule) and reference formulation (tablet). When compared to the tablets, the residence time of the sustained capsules was dramatically prolonged and Cmax Was reduced (P<0.01). The initial release speed was slow and stable. The bioavailability was similar to the common tablets. Conclusions The sustained capsule had showed good pharmacokinetics property of sustained-release in the Beagle dogs.

  14. Effect of blueberry juice on clearance of buspirone and flurbiprofen in human volunteers

    Science.gov (United States)

    Hanley, Michael J; Masse, Gina; Harmatz, Jerold S; Cancalon, Paul F; Dolnikowski, Gregory G; Court, Michael H; Greenblatt, David J

    2013-01-01

    Aim The present study evaluated the possibility of drug interactions involving blueberry juice (BBJ) and substrate drugs whose clearance is dependent on cytochromes P4503A (CYP3A) and P4502C9 (CYP2C9). Methods A 50:50 mixture of lowbush and highbush BBJ was evaluated in vitro as an inhibitor of CYP3A activity (hydroxylation of triazolam and dealkylation of buspirone) and of CYP2C9 activity (flurbiprofen hydroxylation) using human liver microsomes. In clinical studies, clearance of oral buspirone and oral flurbiprofen was studied in healthy volunteers with and without co-treatment with BBJ. Results BBJ inhibited CYP3A and CYP2C9 activity in vitro, with 50% inhibitory concentrations (IC50) of less than 2%, but without evidence of mechanism-based (irreversible) inhibition. Grapefruit juice (GFJ) also inhibited CYP3A activity, but inhibitory potency was increased by pre-incubation, consistent with mechanism-based inhibition. In clinical studies, GFJ significantly increased area under the plasma concentration−time curve (AUC) for the CYP3A substrate buspirone. The geometric mean ratio (GMR = AUC with GFJ divided by AUC with water) was 2.12. In contrast, the effect of BBJ (GMR = 1.39) was not significant. In the study of flurbiprofen (CYP2C9 substrate), the positive control inhibitor fluconazole significantly increased flurbiprofen AUC (GMR = 1.71), but BBJ had no significant effect (GMR = 1.03). Conclusion The increased buspirone AUC associated with BBJ is quantitatively small and could have occurred by chance. BBJ has no effect on flurbiprofen AUC. The studies provide no evidence for concern about clinically important pharmacokinetic drug interactions of BBJ with substrate drugs metabolized by CYP3A or CYP2C9. PMID:22943633

  15. Quantization of buspirone hydrochloride in pure and pharmaceutical formulation by spectrophotometric method

    International Nuclear Information System (INIS)

    A simple and sensitive method is described for the determination of bus pirone hydrochloride in bulk drug and in formulations employing spectrophotometric technique. The method is based on the interaction orbuspirone hydrochloride with ammonium molybdate in acidic media and the absorbance is measured at 700 nm. Beer's Law is obeyed in the range of 5 macro g to 350 micro g/ml and RSD is 0.96% for buspirone hydrochloride. Analytical data for the determination of pure compound is presented along with the application of the proposed method for the analysis of pharmaceutical formulation. (author)

  16. A Comparison of Risperidone and Buspirone for Treatment of Behavior Disorders in Children with Phenylketonuria

    Directory of Open Access Journals (Sweden)

    Afshin FAYYAZI

    2014-12-01

    Full Text Available How to Cite This Article: Fayyazi A, Salari E, Khajeh A, Ghajarpour A. A Comparison of Risperidone and Buspirone for Treatment ofBehavior Disorders in Children with Phenylketonuria. Iran J Child Neurol. 2014 Autumn; 8(4:33-38.AbstractObjectiveMany patients with late-diagnosed phenylketonuria (PKU suffer from severe behavior problems. This study compares the effects of buspirone and risperidone on reducing behavior disorders in these patients.Materials & MethodsIn this crossover clinical trial study, patients with severe behavior disorders after medical examination were randomly divided into two groups of two 8-week crossover treatments with risperidone or buspirone. Patient behavioral disorders before and after treatment by each drug was rated by parents on the Nisonger Child Behavior Rating Form (NCBRF, and after treatment by each drug, were assessed by a physician through clinical global impression (CGI.ResultsThirteen patients were able to complete the therapy period with these two medications.The most common psychiatric diagnoses were intellectual disability accompanied by pervasive developmental disorder NOS, and intellectual disability accompanied by autistic disorder. Risperidone was significantly effective in reducing the NCBRF subscales of hyperactivity disruptive/ stereotypic, and conduct problems. Treatment by buspirone only significantly decreased the severity of hyperactivity, but other behavior aspects showed no significant differences. Assessment of the severity of behavior disorder after treatment by risperidone and buspirone showed significant differences in reducing hyperactivity and masochistic/stereotype.ConclusionAlthough buspirone is effective in controlling hyperactivity in patients with PKU, it has no preference over risperidone. Therefore, it is recommended as an alternative to risperidone.ReferencesSmith I, Nowles JK. Behaviour in early treated phenylketonuria: a systematic review. Eur J Pediatr 2000;159:89-93.Targum SD

  17. Outcomes on the pharmacopsychometric triangle in bupropion-SR vs. buspirone augmentation of citalopram in the STAR*D trial

    DEFF Research Database (Denmark)

    Bech, P; Fava, Maurizio; Trivedi, M H;

    2012-01-01

    Bech P, Fava M, Trivedi MH, Wisniewski SR, Rush AJ. Outcomes on the pharmacopsychometric triangle in bupropion-SR vs. buspirone augmentation of citalopram in the STAR*D trial. Objective: To compare within the framework of a novel pharmacopsychometric triangle, augmentation treatment with bupropion...... Scale (HAM-D(17) ) and of the Inventory of Depressive Symptomatology (IDS-C(30) ), referred to as HAM-D(6) and IDS-C(6) , were focussed on pure antidepressive effect. Side-effects (tolerable vs. intolerable) and quality of life were measured using patient-administered questionnaires. A modified......-C(6) , and IDS-C(30) , but not on the HAM-D(17) . In the domain of side effects, the total scores on the Patient Rated Inventory of Side Effects (PRISE) were reduced significantly more by bupropion-SR than by buspirone (P = 0.03). In the domain of quality of life, the total scores on the Quality...

  18. Effect of the serotonin receptor agonist, buspirone, on immune function in HIV-infected individuals: a six-month randomized, double-blind, placebo-controlled trial

    DEFF Research Database (Denmark)

    Eugen-Olsen, J; Benfield, Thomas; Axen, T E;

    2000-01-01

    , and response to pokeweed mitogen (PWM) in antiretroviral naive HIV-1-infected individuals. METHOD: Twenty-three HIV-infected patients with CD4 T-cell counts above 300 per microL were enrolled in a 6-month double-blinded placebo controlled trial. No patients received antiretroviral therapy during the...... compared to placebo-treated patients was observed. There were no significant differences in CD4 T-cell counts, HIV viral load,or proliferative response to PWM between those receiving placebo and those receiving buspirone. CONCLUSION: Buspirone treatment leads to significant changes in CD8 T-cell count and...

  19. Effect of the serotonin receptor agonist, buspirone, on immune function in HIV-infected individuals: a six-month randomized, double-blind, placebo-controlled trial

    DEFF Research Database (Denmark)

    Eugen-Olsen, Jesper; Benfield, T; Axen, T E;

    2000-01-01

    , and response to pokeweed mitogen (PWM) in antiretroviral naive HIV-1-infected individuals. METHOD: Twenty-three HIV-infected patients with CD4 T-cell counts above 300 per microL were enrolled in a 6-month double-blinded placebo controlled trial. No patients received antiretroviral therapy during the...... compared to placebo-treated patients was observed. There were no significant differences in CD4 T-cell counts, HIV viral load, or proliferative response to PWM between those receiving placebo and those receiving buspirone. CONCLUSION: Buspirone treatment leads to significant changes in CD8 T-cell count and...

  20. Dopamine D3 receptor is necessary for ethanol consumption: an approach with buspirone.

    Science.gov (United States)

    Leggio, Gian Marco; Camillieri, Giovanni; Platania, Chiara B M; Castorina, Alessandro; Marrazzo, Giuseppina; Torrisi, Sebastiano Alfio; Nona, Christina N; D'Agata, Velia; Nobrega, José; Stark, Holger; Bucolo, Claudio; Le Foll, Bernard; Drago, Filippo; Salomone, Salvatore

    2014-07-01

    Mesolimbic dopamine (DA) controls drug- and alcohol-seeking behavior, but the role of specific DA receptor subtypes is unclear. We tested the hypothesis that D3R gene deletion or the D3R pharmacological blockade inhibits ethanol preference in mice. D3R-deficient mice (D3R(-/-)) and their wild-type (WT) littermates, treated or not with the D3R antagonists SB277011A and U99194A, were tested in a long-term free choice ethanol-drinking (two-bottle choice) and in a binge-like ethanol-drinking paradigm (drinking in the dark, DID). The selectivity of the D3R antagonists was further assessed by molecular modeling. Ethanol intake was negligible in D3R(-/-) and robust in WT both in the two-bottle choice and DID paradigms. Treatment with D3R antagonists inhibited ethanol intake in WT but was ineffective in D3R(-/-) mice. Ethanol intake increased the expression of RACK1 and brain-derived neurotrophic factor (BDNF) in both WT and D3R(-/-); in WT there was also a robust overexpression of D3R. Thus, increased expression of D3R associated with activation of RACK1/BDNF seems to operate as a reinforcing mechanism in voluntary ethanol intake. Indeed, blockade of the BDNF pathway by the TrkB selective antagonist ANA-12 reversed chronic stable ethanol intake and strongly decreased the striatal expression of D3R. Finally, we evaluated buspirone, an approved drug for anxiety disorders endowed with D3R antagonist activity (confirmed by molecular modeling analysis), that resulted effective in inhibiting ethanol intake. Thus, DA signaling via D3R is essential for ethanol-related reward and consumption and may represent a novel therapeutic target for weaning. PMID:24584330

  1. First Use of a New Device for Administration of Buspirone and Acetaminophen to Suppress Shivering During Therapeutic Hypothermia.

    Science.gov (United States)

    Honasoge, Akilesh; Parker, Braden; Wesselhoff, Kelly; Lyons, Neal; Kulstad, Erik

    2016-03-01

    Therapeutic hypothermia or targeted temperature management has been used after cardiac arrest to improve neurological outcomes and mortality. However, a side effect of temperature modulation is a centrally mediated shivering response. The Columbia Anti-Shivering Protocol sets up a systematic method of intravenous (IV) and oral medication escalation to suppress this response and preserve the benefits of this therapy. We present the case of a 59-year-old male who began shivering after therapeutic hypothermia for cardiac arrest, leading to a persistent rise in core temperature despite adequate sedation. He was also found to have gastric contents similar to coffee grounds through nasogastric tube suction. The shivering was effectively suppressed and the rising core temperature plateaued using rectal acetaminophen and buspirone administered by means of a novel device, the Macy Catheter. Also, when used in conjunction with other protocol-driven medications, the patient was able to achieve a core temperature of 33°C. The Macy Catheter appears to be a useful approach to rectally administer buspirone and acetaminophen, using an easy-to-place, nonsterile atraumatic device that requires no radiographic confirmation of placement. PMID:26807775

  2. The 5-HT1A agonists 8-OH-DPAT, buspirone and ipsapirone attenuate stress-induced anorexia in rats.

    Science.gov (United States)

    Dourish, C T; Kennett, G A; Curzon, G

    1987-01-01

    The effects of 5-HT agonists and antagonists, benzodiazepine anxiolytics and tricyclic antidepressants on restraint stress-induced anorexia in rats were examined. The selective 5-HT(1A) agonists 8-hydroxy-2-(di- n-propylamino)tetralin (8-OH-DPAT), buspirone and ipsapirone, when injected 2 h after the termination of stress, attenuated stress-induced anor exia and body weight loss. The effects of 8-OH-DPAT on stress-induced anorexia were blocked by the 5-HT(1A) antagonist spiperone but not by the 5-HT(2) antagonist ketanserin. The preferential 5-HT(1B) agonists RU-24969 and quipazine induced anorexia in unstressed rats and tended to supplement the anorectic effects of stress. The benzodiazepines chlordiazepoxide and diazepam and the 5-HT antagonist cyproheptadine had no effect on stress-induced anorexia, when given (like the 5-HT(1A) agonists) 2 h after the stress. Similarly, daily injection for 2 weeks of the tricyclic antidepressants desipramine and sertraline had no beneficial effect. The data suggest that 8-OH-DPAT, buspirone and ipsapirone attenuate stress-induced anorexia in rodents by a hyperphagic action on 5-HT(1A) receptors. PMID:22158750

  3. Treatment of Anxiety Disorders and Comorbid Alcohol Abuse with Buspirone in a Patient with Antidepressant-Induced Platelet Dysfunction: A Case Report

    Directory of Open Access Journals (Sweden)

    Mir Mazhar

    2013-01-01

    Full Text Available The risk of abnormal bleeding with serotonin reuptake inhibitors has been known, but there is insufficient evidence base to guide pharmacological treatment of anxiety in patients with underlying haematological conditions. The following case report is about a 50-year-old female with generalized anxiety disorder, social phobia, obsessive compulsive disorder, and alcohol abuse where pharmacological treatment of anxiety symptoms has been difficult as it would lead to bruising due to the patient’s underlying qualitative platelet dysfunction. Treatment with venlafaxine, citalopram, escitalopram, and clomipramine resulted in improvement and anxiety symptoms, as well as reduction in alcohol use, but pharmacological treatment has to be discontinued because of bruising and hematomas. In view of an active substance use disorder, benzodiazepines were avoided as a treatment option. The patient’s anxiety symptoms and comorbid alcohol abuse responded well to pharmacological treatment with buspirone which gradually titrated up to a dose of 30 mg BID. Patient was followed for around a six-month period while she was on buspirone before being discharged to family doctor’s care. Buspirone is unlikely to have a significant effect on platelet serotonin transponder and could be an effective alternative for pharmacological treatment of anxiety in patients with a bleeding diathesis.

  4. Enhanced bioavailability of buspirone from reservoir-based transdermal therapeutic system, optimization of formulation employing Box-Behnken statistical design.

    Science.gov (United States)

    Gannu, Ramesh; Palem, Chinna Reddy; Yamsani, Shravan Kumar; Yamsani, Vamshi Vishnu; Yamsani, Madhusudan Rao

    2010-06-01

    The purpose of the present study was to develop and optimize reservoir-based transdermal therapeutic system (TTS) for buspirone (BUSP), a low bioavailable drug. A three-factor, three-level Box-Behnken design was employed to optimize the TTS. Hydroxypropyl methylcellulose, D: -limonene and propylene glycol were varied as independent variables; cumulative amount permeated across rat abdominal skin in 24 h, flux and lag time were selected as dependent variables. Mathematical equations and response surface plots were used to relate the dependent and independent variables. The statistical validity of polynomials was established, and optimized formulation factors were selected by feasibility and grid search. Validation of the optimization study with seven confirmatory runs indicated high degree of prognostic ability of response surface methodology. BUSP-OPT (optimized formulation) showed a flux 104.6 microg cm(-2) h(-1), which could meet target flux. The bioavailability studies in rabbits showed that about 2.65 times improvement (p statistical design and could provide an effective treatment in the management of anxiety.

  5. Effects of buspirone on the immediate positive and delayed negative properties of intravenous cocaine as measured in the conditioned place preference test.

    Science.gov (United States)

    Ettenberg, Aaron; Bernardi, Rick E

    2007-05-01

    In prior work, we have demonstrated that the behavioral effects of cocaine adhere to the predictions of the opponent-process theory of drug action. Animals develop conditioned place preferences for distinct locations paired with the immediate effects of IV cocaine, but learn to avoid places paired with the effects present 15-min post-injection. It was of interest to assess the putative role of 5-HT in producing the negative properties of cocaine since cocaine acts to inhibit the reuptake of serotonin (5-HT) and since such actions have been associated with anxiogenic consequences. Male rats were administered a reinforcing dose of cocaine (1.0 mg/kg IV) and then placed - either immediately or after a 15-min delay - into one side of a two-compartment (black-white) conditioned place preference (CPP) box for 5-min. On alternate days, the animals received IV saline injections and were placed in the opposite side of the CPP box. This continued for eight days after which animals had experienced 4 pairings of cocaine with one side (black or white) of the CPP apparatus, and 4 saline pairings with the opposite side. Other groups of rats were treated identically except that 30-min prior to placement into the apparatus, these animals received an IP injection of saline or buspirone (a partial 5-HT1A agonist) at a dose that we have shown to be anxiolytic (2.5 mg/kg IP). Control animals experienced either buspirone or saline pretreatments without cocaine. Our results confirm that animals increase the time spent on the side paired with the immediate effects of cocaine (compared to baseline), but tend to avoid the side paired with effects present 15-min post-injection. Buspirone had no effect on the immediate rewarding properties of cocaine, but completely reversed the negative properties present 15-min post-cocaine. These results are consistent with the view that attenuation of 5-HT neurotransmission (via the autoreceptor agonist properties of buspirone) can reverse the negative

  6. 丁螺环酮治疗小脑性共济失调%The Treatment of Cerebellar Ataxia with Buspirone Hydrochloride

    Institute of Scientific and Technical Information of China (English)

    邬剑军; 蒋雨平

    2001-01-01

    目的:探讨5-HT1A受体激动剂丁螺环酮改善共济失调症状的作用。方法:应用评分计分法观察丁螺环酮治疗24例共济失调患者3个月。结果:治疗前后共济失调评分,包括稳定性、协调性、构音、眼球运动各方面的差异均有显著意义(P0.05)。结论:丁螺环酮短期内可以有效地改善患者小脑性共济失调的症状。%Aim: To evaluate the efficacy of buspirone hydrochloride, a serotonin (5-hydroxytrypamine1A) agonist, in treating patients with cerebellar ataxia. Methods:Open-table study in which 24 patients received buspimne hydrochloride for three months. Results:All who completed the study showed significant improvement in ataxia rating scale, including stability, coordination, articulation, ocular movement, but not in the Hamilton anxiety scale. Conclusion:Short-term treatment with buspirone hydrochloride can improve the symptoms of patients with cerebellar ataxia.

  7. Effect of Buspirone, Fluoxetine and 8-OH-DPAT on Striatal Expression of Bax, Caspase-3 and Bcl-2 Proteins in 6-Hydroxydopamine-Induced Hemi-Parkinsonian Rats

    OpenAIRE

    Hamdollah Sharifi; Alireza Nayebi; Safar Farajnia; Rasool Haddadi

    2015-01-01

    Purpose: The exact pathogenesis of sporadic parkinson’s disease (PD) is still unclear. Numerous evidences suggest involvement of apoptosis in the death of dopaminergic neurons. In this study we investigated the effect of sub-chronic administration of buspirone, fluoxetine and 8-hydroxy-2-[di-n-propylamino]tetralin (8-OH-DPAT) in 6-hydroxydopamine (6-OHDA)-lesioned rats and assayed striatal concentrations of apoptotic (Bax, Caspase3) and anti-apoptotic (Bcl-2) proteins. M...

  8. 舍曲林联合丁螺环酮治疗抑郁症对照观察%Sertraline plus buspirone in the treatment of depression

    Institute of Scientific and Technical Information of China (English)

    杜丽娜

    2015-01-01

    目的:探讨舍曲林联合丁螺环酮治疗抑郁症的临床疗效及安全性。方法将87例抑郁症患者随机分为两组,均予以舍曲林治疗,研究组在此基础上联合丁螺环酮治疗,观察8周。治疗前后采用汉密顿抑郁量表评定临床疗效,副反应量表评定不良反应。结果治疗后两组汉密顿抑郁量表评分均较治疗前显著降低(P<0.01),研究组显著低于对照组(P<0.01);两组副反应量表评分比较差异无显著性(P>0.05)。结论舍曲林联合丁螺环酮治疗抑郁症疗效显著,安全性高,优于单用舍曲林治疗。%Objective To explore the efficacy and safety of sertraline plus buspi‐rone in the treatment of depression .Methods Eighty‐seven depression patients were randomly divided into two groups treated with sertraline ,on this basis re‐search group was coupled with buspirone for 8 weeks .Efficacies were assessed with the Hamilton Depres‐sion Scale (HAMD) before and after treatment and adverse reactions with the Treatment Emergent Symp‐tom Scale (TESS) .Results After treatment the HAMD scores of both groups lowered compared with pretreatment (P 0 .05) .Conclusion Sertraline plus buspirone has an evident effect and higher safety compared with single sertraline in the treatment of depression .

  9. Modulatory effect of the 5-HT1A agonist buspirone and the mixed non-hallucinogenic 5-HT1A/2A agonist ergotamine on psilocybin-induced psychedelic experience.

    Science.gov (United States)

    Pokorny, Thomas; Preller, Katrin H; Kraehenmann, Rainer; Vollenweider, Franz X

    2016-04-01

    The mixed serotonin (5-HT) 1A/2A/2B/2C/6/7 receptor agonist psilocybin dose-dependently induces an altered state of consciousness (ASC) that is characterized by changes in sensory perception, mood, thought, and the sense of self. The psychological effects of psilocybin are primarily mediated by 5-HT2A receptor activation. However, accumulating evidence suggests that 5-HT1A or an interaction between 5-HT1A and 5-HT2A receptors may contribute to the overall effects of psilocybin. Therefore, we used a double-blind, counterbalanced, within-subject design to investigate the modulatory effects of the partial 5-HT1A agonist buspirone (20mg p.o.) and the non-hallucinogenic 5-HT2A/1A agonist ergotamine (3mg p.o.) on psilocybin-induced (170 µg/kg p.o.) psychological effects in two groups (n=19, n=17) of healthy human subjects. Psychological effects were assessed using the Altered State of Consciousness (5D-ASC) rating scale. Buspirone significantly reduced the 5D-ASC main scale score for Visionary Restructuralization (VR) (ppsilocybin-induced 5D-ASC main scale scores. The present finding demonstrates that buspirone exerts inhibitory effects on psilocybin-induced effects, presumably via 5-HT1A receptor activation, an interaction between 5-HT1A and 5-HT2A receptors, or both. The data suggest that the modulation of 5-HT1A receptor activity may be a useful target in the treatment of visual hallucinations in different psychiatric and neurological diseases.

  10. Modulatory effect of the 5-HT1A agonist buspirone and the mixed non-hallucinogenic 5-HT1A/2A agonist ergotamine on psilocybin-induced psychedelic experience.

    Science.gov (United States)

    Pokorny, Thomas; Preller, Katrin H; Kraehenmann, Rainer; Vollenweider, Franz X

    2016-04-01

    The mixed serotonin (5-HT) 1A/2A/2B/2C/6/7 receptor agonist psilocybin dose-dependently induces an altered state of consciousness (ASC) that is characterized by changes in sensory perception, mood, thought, and the sense of self. The psychological effects of psilocybin are primarily mediated by 5-HT2A receptor activation. However, accumulating evidence suggests that 5-HT1A or an interaction between 5-HT1A and 5-HT2A receptors may contribute to the overall effects of psilocybin. Therefore, we used a double-blind, counterbalanced, within-subject design to investigate the modulatory effects of the partial 5-HT1A agonist buspirone (20mg p.o.) and the non-hallucinogenic 5-HT2A/1A agonist ergotamine (3mg p.o.) on psilocybin-induced (170 µg/kg p.o.) psychological effects in two groups (n=19, n=17) of healthy human subjects. Psychological effects were assessed using the Altered State of Consciousness (5D-ASC) rating scale. Buspirone significantly reduced the 5D-ASC main scale score for Visionary Restructuralization (VR) (pergotamine did not show any effects on the psilocybin-induced 5D-ASC main scale scores. The present finding demonstrates that buspirone exerts inhibitory effects on psilocybin-induced effects, presumably via 5-HT1A receptor activation, an interaction between 5-HT1A and 5-HT2A receptors, or both. The data suggest that the modulation of 5-HT1A receptor activity may be a useful target in the treatment of visual hallucinations in different psychiatric and neurological diseases. PMID:26875114

  11. Augmentation effect of buspirone in the treatment of treatment-refractory schizophrenia%丁螺环酮对难治性精神分裂症治疗的增效作用

    Institute of Scientific and Technical Information of China (English)

    罗世芳; 曾德志; 樊学文; 罗建武

    2012-01-01

    目的:探讨丁螺环酮对难治性精神分裂症(TRS)治疗的增效作用与安全性. 方法:80例TRS患者随机分入合用组(氯氮平+丁螺环酮)和氯氮平组,每组40例,观察治疗12周.采用阳性和阴性症状量表(PANSS)和治疗中出现的症状量表(TESS)分别评定临床疗效和不良反应. 结果:在治疗2、4、12周,合用组临床疗效优于对照组(P均<0.05);两组干预后各因子积分和总分均较入组前显著下降(P均<0.001);阳性因子积分和总分,干预与时间存在交互效应(P<0.01);总分存在组间差别(P<0.05);同期对照比较,除入组后8周阴性因子积分和12周阴性因子和一般精神病理因子积分外,其余各时点各因子积分和总分,合用组减分幅度大于对照组(P<0.05).不良反应总发生率两组间差异无显著性(P>0.05). 结论:丁螺环酮对氯氮平治疗难治性精神分裂症有一定的增效作用,且不增加不良反应.%Objective: To explore the augmentation effect and safety of buspirone in the treatment of the treatment-refractory schizophrenia. Method:All 80 patients with the treatment-refractory schizophrenia were randomly assigned to combined groups (treated with clozapine combined with buspirone) and clozapine group for 12 weeks. Each had 40 cases. The positive and negative syndrome scale (PANSS) and treatment emergent side effect scale (TESS) were used to evaluate the efficacy and adverse effect respectively. Results: After the 2,4,12 weeks treatment,the clinical efficacy in the combined group was significantly better than that in the clozapine group ( all P 0.05). Conclusion: Buspirone can significantly improve the efficacy of clozapine in the treatment of the treatment-refractory schizophrenia and wont add adverse effect also.

  12. Transdermal percutaneous absoirption test of buspirone hydrochloride paste in vivo and determi-nation of plasma samples%盐酸丁螺环酮贴剂体内透皮吸收试验及血浆样品测定

    Institute of Scientific and Technical Information of China (English)

    赵维娟; 张梅; 杜洪; 许景峰

    2009-01-01

    OBJECTIVE To study the absorption of the buspirone hydrochloride transdermal paste in vivo and the method of assay in plasma. METHODS HPLC was used to determine the content of buspirone hydrochloride in rabbit plasma.RESULTS The detection vavelength of HPLC was 237 nm, acetonitrile-methanol-water-0.1 mol·L~(-1) sodium acetate buffer (pH 5.0) (38:10:51:1) was used as the mobile phase and there was a good linear relationship of hydrochloric acid in plasma in the range of 1-100μg·L~(-1); buspirone hydrochloride transdermal delivery patches have good skin permeability. After 24 hours of single administration of 12 mg·kg~(-1), the concentration of the drug in plasma was at steady fluctuations within a certain range. CONCLUSION The method is sensitive,accurate and good reproducible for the determination of the plasma concentra-tion of buspirone hydrochloride. This will provide scientific references for the rational transderrnal drug delivery formulations and the design evaluation in vivo.%目的:研究盐酸丁螺环酮贴剂的体内透皮吸收作用及建立血浆中药物含量测定方法.方法:采用兔活体皮肤透过试验,以高效液相色谱法测定血浆中盐酸丁螺环酮的含量.结果:高效液相色谱法在237 nm,以乙腈-甲醇-水-0.1 mol·L~(-1)醋酸钠缓冲液(pH 5.0)(38:10:51:1)为流动相测定,血浆中盐酸丁螺环酮在1~100μg·L~(-1)范围内呈良好的线性关系;盐酸丁螺环酮贴剂经皮给药具有良好的皮肤渗透性,单次贴敷给药12 mg·kg~(-1),24 h内血浆中药物浓度在一定范围内平稳波动,且作用时间大于24 h.结论:采用本法检测血浆中药物含量,灵敏、准确,重复性好;本实验方法为经皮给药制剂的深入研究及处方设计的合理性评价提供了的参考依据.

  13. ComParison of treatment effect of sertraline single and combination with different doses of busPirone for maJor dePression%舍曲林单用与合并不同剂量丁螺环酮治疗抑郁症患者的对照研究

    Institute of Scientific and Technical Information of China (English)

    付佳林; 汤臻; 朱峰; 刘期春; 伏天; 赵林

    2016-01-01

    目的:探讨不同剂量丁螺环酮对舍曲林抗抑郁的快速起效作用(ROAA)。方法:本研究是一项为期6周、不同剂量、随机、开放、对照的临床实验。90例抑郁症患者随机分为对照组30例(单一舍曲林)、舍曲林联合低剂量丁螺环酮(低剂量组)30例和舍曲林联合高剂量丁螺环酮(高剂量组)30例。采用汉密尔顿抑郁量表(HAMD)、汉密尔顿焦虑量表(HAMA)、临床总体印象表(CGI)等进行临床评估。观察治疗1周丁螺环酮是否使舍曲林的抗抑郁作用快速起效,并进一步评估第2、4、6周的临床差异。结果:以基线、治疗1周、治疗2周、治疗4周、治疗6周为观察点,3组被试无论 HAMD 总分还是 HAMA 总分,组间主效应不显著(P ﹥0.05),时间主效应均显著(P 均﹤0.01),组别×时间交互效应均显著(P 均﹤0.05)。治疗1周,对照组5例起效(16.7%),低剂量组8例起效(26.7%),高剂量组14例(46.7%)起效,3组间差异有统计学意义(χ2=6.67,P =0.036),事后检验对照组与高剂量组差异有统计学意义(P ﹤0.05)。3组间不良反应发生率差异无统计学意义(χ2=0.09,P ﹥0.05)。结论:高剂量丁螺环酮对舍曲林的抗抑郁作用有快速起效的作用,安全有效。%ObJective:To explore the rapid response of different doses of buspirone in combination with sertraline on major depression. Method:This study was an open,controlled,randomized,clinical trial,lasting 6 weeks. 90 patients were randomly assigned to controlled groups(30 cases,treated with sertraline ),low-dose group(30 cases,treated with low dose buspirone in combination with sertraline ),and high-dose group(30 ca-ses,treated with high dose buspirone in combination with sertraline ). Clinical effects were evaluated with Ham-ilton depression scale(HAMD),Hamilton anxiety scale(HAMA)and clinical general impression

  14. Clinical efficacy and safety of Duloxetine combined with Buspirone in treatment of the somatoform disorders%度洛西汀联合丁螺环酮治疗躯体形式障碍患者的疗效及安全性观察

    Institute of Scientific and Technical Information of China (English)

    韩跃平; 石顺治

    2016-01-01

    Objective:To discuss efficacy and safety of Duloxetine combined with Buspirone in treatment of patients with som-atoform disorders. Methods:71 patients with somatoform disorders were randomly divided into research group(Duloxetine combined with Buspirone group)(n=36)and control group(Duloxetine group)(n= 35),and were treated for 6 weeks. The efficacies of the two groups were evaluated and compared with Hamilton anxiety scale(HAMA)and clinical global impression(CGI)before and 2,4 and 6 weeks after the treatment. Results:The scores of HAMA of the two groups decreased significantly 2,4 and 6 weeks after the treatment(P<0. 01). Compared with the control group,the scores of HAMA decreased more significantly in the research group 4 and 6 weeks after the treatment(P<0. 05). The scores of CGI showed that:the research group received obvious efficacy 2 weeks after the treatment and the scores decreased obviously than control groups in 4th and 6th weeks(P<0. 05). Conclusions:Duloxetine combined with Buspirone is more effective in the treatment of the patients with somatoform disorder than duloxetine only.%目的:观察度洛西汀联合丁螺环酮治疗躯体形式障碍患者的疗效及安全性。方法:将71例躯体形式障碍患者随机分为研究组和对照组。研究组患者36例,给予度洛西汀联合丁螺环酮治疗;对照组患者35例,单独给予度洛西汀治疗。两组患者的疗程均为6周。治疗前及治疗后第2、4、6周,采用汉密尔顿焦虑量表(HAMA)和临床疗效总评量表(CGI)对两组患者的疗效进行评定和比较。结果:治疗后2、4、6周与治疗前相比较,两组患者的评分均明显降低(P<0.01);治疗后第4、6周,研究组患者的评分明显低于对照组(P<0.05);CGI 评分显示:研究组患者自第2周开始出现明显疗效,且第4、6周评分优于对照组(P<0.05)。结论:度洛西汀联合丁螺环酮治疗躯体形式障碍患者的

  15. 芪参复康胶囊、丁螺环酮对焦虑症患者事件相关电位P300的影响%Comparison of event-related potentials P300 change in patients with anxiety disorder and treated with Qishen Fukang capsules or Buspirone

    Institute of Scientific and Technical Information of China (English)

    张连强; 陈玖; 杨来启; 李亚萍; 王大刚; 邓自和; 张彦; 李新田

    2012-01-01

    Objective To compare the effects of Qishen Fukang capsules and Buspirone on cognitive function in anxiety disorders. Methods 70 patients with anxiety disorders from Center for Mental Disease Control and Prevention of Third Hospital of PLA were enrolled as research group. The research group was divided into Qishen Fukang capsules treated group (Chinese medicine group, CMG, 35 cases) and Buspirone treated group (Western medicine group, WMG, 35 cases) by the method of the random number table. The research groups were assessed with the Hamilton Anxiety Scale (HAMA) and measured with evoked event-related potential P300 change before and after 6 weeks treatment. Another 36 healthy subjects were involved as controls and they were given simultaneously the same tests. The effect of Qishen Fukang capsules and Buspirone on cognitive function in anxiety disorder before and after treatment was compared. Results (1)Comparing to prior-treatment [CMG (27. 4±5. 4) score vs. WMG (27.2 ± 6.2) score], the HAMD scores of patients [CMG (5. 2 ± 2. 2) score vs. WMG (6. 7 ± 2. 6) score] were decreased significantly (P0. 05) while the P3 latency was still longer and the N2, P3 amplitudes were still significantly lower (all P< 0.05) in the WMG post - treatment. Conclusions Qishen Fukang capsules and Fluoxetine can improve significantly clinical symptoms and cognitive function in anxiety disorders. Qishen Fukang capsule is superior to Buspirone on improving information processing, recognition, and coding of sensation and perception.%目的 评价芪参复康胶囊、丁螺环酮对焦虑症患者认知功能的影响.方法 将本院70例焦虑症患者按随机数字表法分两组,中药组(35例)给予芪参复康胶囊,西药组(35例)给予丁螺环酮.两组患者于治疗前、治疗后6周进行HAMA评定及P300检查,另选36名健康志愿者(对照组)行P300检查.分析两组患者治疗前后对认知功能的影响.结果 (1)与治疗前

  16. 丁螺环酮对广泛性焦虑症患者情绪图片认知偏倚的影响%Effect of buspirone treatment on cognitive bias to the emotional facial information in generalized anxiety disorder

    Institute of Scientific and Technical Information of China (English)

    姚建军; 张紫娟; 周振和; 王军; 陈琳

    2012-01-01

    Objective:To investigate the effect of buspirone treatment on cognitive bias to the emotional facial information in patients with generalized anxiety disorder (GAD). Method: 30 patients met Chinese classification of mental disorders and diagnostic crileria-3 for GAD were enrolled as research group and 30 gender, age matched healthy persons enrolled as control group. Patients were treated with buspirone for 8weeks. All participants measured with dot-probe task of emotional facial information at base and after 8 weeks. Reaction times ( RTs) and attentional bias scores were compared respectively. Results: After 8 weeks,HAMA scores in research group were lower than that at base (7.29 ± 1.56 Vs. 16.93 ± 2.11) (t = 3. 326, P = 0.003 ). A repeated measure ANOVA revealed a significant probe site main effect, reaction times of antarafacial site were longer than that of homonymy site( P < 0. 05 ). It revealed a significant probe site and group interaction ( P = 0.000),a significant emotional facial information type and probe site interaction (P = 0.000) ,and a significant emotional facial information type x probe site x group interaction (P = 0.002). LSD test showed that RTs of antarafacial site to fear facial information in research group were longer than that of homonymy site (P =0.001). RTs and attention bias scores of antarafacial site to fear facial information after 8 weeks in research group were lower than that at base(P= 0.006). Conclusion: Patients with GAD had the cognitive bias to the fear facial emotional stimulus. Buspirone treatment might improve the cognitive bias.%目的:探讨丁螺环酮对广泛性焦虑症患者情绪图片信息认知偏倚的影响. 方法:选择符合中国精神障碍分类与诊断标准第3版广泛性焦虑症诊断标准的30例患者作为研究组,30名与研究组性别、年龄匹配的健康人作为对照组.研究组给予丁螺环酮治疗8周.两组分别在治疗前和治疗8周后进行情绪图片刺激的点探测

  17. 75 FR 64310 - Determination That BUSPAR (Buspirone Hydrochloride) Tablets, 10 Milligrams, 15 Milligrams, and 30...

    Science.gov (United States)

    2010-10-19

    ... drug was withdrawn from sale for reasons of safety or effectiveness (21 CFR 314.162). Under Sec. 314... sale for reasons of safety or effectiveness before an ANDA that refers to that listed drug may be... must determine whether a listed drug was withdrawn from sale for reasons of safety or...

  18. Anxiolytic-like actions of buspirone in a runway model of intravenous cocaine self-administration

    OpenAIRE

    Ettenberg, Aaron; Bernardi, Rick E.

    2006-01-01

    In previous work from our laboratory, rats traversing a straight alley for a reward of IV cocaine have been observed to develop ambivalence about entering the goal box. Over trials, animals repeatedly run toward the goal box, stop at the entry point, and then retreat back toward the start box. This unique pattern of retreat behavior has been shown to reflect a form of “approach-avoidance conflict” that stems from the subjects' concurrent positive (cocaine reward) and negative (cocaine-induced...

  19. Trazodone vs buspirone in treating generalized anxiety%曲唑酮与丁螺环酮治疗广泛性焦虑症的比较

    Institute of Scientific and Technical Information of China (English)

    郭本玉; 季卫东; 陈佐明

    2003-01-01

    目的:比较曲唑酮和丁螺环酮治疗广泛性焦虑症的疗效及安全性.方法:60例广泛性焦虑症病人分成2组,曲唑酮组男性18例,女性12例,给予曲唑酮每日50~150 mg,分2次口服×4 wk;丁螺环酮组男性16例,女性14例,给予丁螺环酮5~30 mg,分2次口服×4 wk.结果:曲唑酮组总有效率83 %,丁螺环酮组总有效率70 %,2组疗效比较经Ridit分析,P>0.05.药物不良反应发生率曲唑酮组与丁螺环酮组差异无显著意义(P>0.05).结论:曲唑酮治疗广泛性焦虑症安全有效,其疗效与丁螺环酮相似.

  20. Treatment of Anxiety Disorders and Comorbid Alcohol Abuse with Buspirone in a Patient with Antidepressant-Induced Platelet Dysfunction: A Case Report

    OpenAIRE

    Mir Mazhar; Tariq Hassan; Tariq Munshi

    2013-01-01

    The risk of abnormal bleeding with serotonin reuptake inhibitors has been known, but there is insufficient evidence base to guide pharmacological treatment of anxiety in patients with underlying haematological conditions. The following case report is about a 50-year-old female with generalized anxiety disorder, social phobia, obsessive compulsive disorder, and alcohol abuse where pharmacological treatment of anxiety symptoms has been difficult as it would lead to bruising due to the patient’s...

  1. 曲唑酮与丁螺环酮治疗焦虑症的对照研究%A Clinical Control Study of Trazodone and Buspirone in Treatment of Generalized Anxiety Disorder

    Institute of Scientific and Technical Information of China (English)

    刘国雄; 蔡颖莲

    2007-01-01

    目的 比较曲唑酮与丁螺环酮治疗焦虑症的临床疗效、安全性及耐受性.方法 将符合CCMD-3广泛性焦虑症诊断标准的患者随机分为曲唑酮与丁螺环酮组治疗6周,采用汉密尔顿焦虑量表(HAMA)、临床总体印象表(CGI)和不良反应症状量表(TESS)评定疗效和副反应.结果 曲唑酮与丁螺环酮治疗广泛性焦虑症的疗效相似,但副反应比丁螺环酮小.结论 曲唑酮与丁螺环酮治疗焦虑症的疗效相当,不良反应轻,安全性好.

  2. 盐酸丁螺环酮治疗反社会人格障碍攻击行为对照研究%Antiaggressive Effect of Buspirone in Antisocial Personality Disorders

    Institute of Scientific and Technical Information of China (English)

    王小平; 徐莉萍; 李凌江; 孙业华; 刘铁桥; 蒋少艾; 张向晖

    2002-01-01

    @@ 动物和人体实验提示,攻击行为与中枢五羟色胺(5-HT)功能呈负相关,即中枢5-HT功能不足是攻击行为的生物学基础[1,2].有研究认为,五羟色胺系统可能是通过5-HT1A受体或5-HT1B受体来调节攻击行为[3,4].最近,王小平等[5]的动物试验证实,盐酸丁螺环酮可以减少隔离小鼠的攻击行为.为了进一步了解盐酸丁螺环酮对人体的抗攻击效应,本研究以反社会人格障碍患者为研究对象,对盐酸丁螺环酮的抗攻击效应进行对照研究.

  3. Drug: D00702 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 080(3350) Neuroactive ligand-receptor interaction Enzyme: CYP3A [HSA:1576 1577 1551] map07030 Anxiolytics ma...e derivatives N05BE01 Buspirone D00702 Buspirone hydrochloride (USP) USP drug classification [BR:br08302] Anxiolytics Anxi

  4. Drug: D07593 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 3350) Neuroactive ligand-receptor interaction Enzyme: CYP3A [HSA:1576 1577 1551] map07030 Anxiolytics map072...rivatives N05BE01 Buspirone D07593 Buspirone (INN) USP drug classification [BR:br08302] Anxiolytics Anxiolyt

  5. Mirtazapine

    Science.gov (United States)

    ... antidepressants. It works by increasing certain types of activity in the brain to maintain mental balance. ... Aventyl, Pamelor), protriptyline (Vivactil), and trimipramine (Surmontil); certain antifungals such as ketoconazole (Nizoral); buspirone; carbamazepine (Carbatrol, Epitol, ...

  6. 丁螺环酮与氯硝西泮治疗广泛性焦虑症的临床对照研究%A comparative study of buspirone and clonazepam in the treatment of patients with generalized anxiety disorder

    Institute of Scientific and Technical Information of China (English)

    商振美; 吴多琛; 陈光金; 邢向忠

    2004-01-01

    目的评价丁螺环酮治疗广泛性焦虑症的临床疗效和副反应.方法对288例符合CCMD-3诊断标准的广泛性焦虑症患者,随机分为两组,分别为丁螺环酮组(144例),氯硝西泮组(144例)进行治疗,疗程6周.采用焦虑自评量表(SAS)、Hamilton焦虑量表(HAMA)和副反应量表(TESS)评定疗效和副反应.结果丁螺环酮与氯硝西泮对广泛性焦虑症均有显著疗效.两组间疗效差异无显著性,(P>0.05),丁螺环酮副反应明显少于氯硝西泮(P<0.01).结论丁螺环酮治疗广泛性焦虑症安全有效,副反应轻微.

  7. Synthesis, in vitro binding studies and docking of long-chain arylpiperazine nitroquipazine analogues, as potential serotonin transporter inhibitors.

    Science.gov (United States)

    Jarończyk, Małgorzata; Wołosewicz, Karol; Gabrielsen, Mari; Nowak, Gabriel; Kufareva, Irina; Mazurek, Aleksander P; Ravna, Aina W; Abagyan, Ruben; Bojarski, Andrzej J; Sylte, Ingebrigt; Chilmonczyk, Zdzisław

    2012-03-01

    It is well known that 6-nitroquipazine exhibits about 150-fold higher affinity for the serotonin transporter (SERT) than quipazine and recently we showed quipazine buspirone analogues with high to moderate SERT affinity. Now we have designed and synthesized several 6-nitroquipazine buspirone derivatives. Unexpectedly, their SERT binding affinities were moderate, and much lower than that of the previously studied quipazine buspirone analogues. To explain these findings, docking studies of both groups of compounds into two different homology models of human SERT was performed using a flexible target-ligand docking approach (4D docking). The crystal structures of leucine transporter from Aquifex aeolicus in complex with leucine and with tryptophan were used as templates for the SERT models in closed and outward-facing conformations, respectively. We found that the latter conformation represents the most reliable model for binding of buspirone analogues. Docking into that model showed that the nitrated compounds acquire a rod like shape in the binding pocket with polar groups (nitro- and imido-) at the ends of the rod. 6-Nitro substituents gave steric clashes with amino acids located at the extracellular loop 4, which may explain their lower affinity than corresponding quipazine buspirone analogues. The results from the present study may suggest chemical design strategies to improve the SERT modulators. PMID:22309909

  8. Placebo Medication Use for Behavior Management in an Adult with Autism

    Science.gov (United States)

    Kroeger, K. A.; Brown, Jennifer

    2011-01-01

    Buspar (buspirone) is an anxiolytic medication used to reduce symptoms associated with anxiety. The current study provides a case description of a man diagnosed with autistic disorder where Buspar was prescribed on an "as needed" basis in order to decelerate tantrum behavior associated with undifferentiated anxiety. After successful reduction of…

  9. Modulation of reflexly evoked vagal bradycardias by central 5-HT1A receptors in anaesthetized rabbits

    OpenAIRE

    Skinner, Matthew R; Ramage, Andrew G; Jordan, David

    2002-01-01

    The role of central 5-HT1A receptors in the control of the bradycardia and changes in central respiratory drive, renal nerve activity and blood pressure evoked by stimulating cardiopulmonary afferents with phenylbiguanide, baroreceptors by electrical stimulation of the aortic nerve and chemoreceptors by injections of sodium cyanide (NaCN) in atenolol-pretreated anaesthetized rabbits were studied.Buspirone (100 μg kg−1; i.c.) potentiated the bradycardia (increase in R-R interval) and the chang...

  10. The drug treatment of delayed ejaculation.

    Science.gov (United States)

    Abdel-Hamid, Ibrahim A; Elsaied, Moustafa A; Mostafa, Taymour

    2016-08-01

    Delayed ejaculation (DE) is an uncommon and a challenging disorder to treat. It is often quite concerning to patients and it can affect psychosocial well-being. Here we reviewed how DE is treated pharmacologically .We also highlighted specific settings where drugs could be introduced to medical practice. Electronic databases were searched from 1966 to February 2016, including PubMed MEDLINE, EMBASE, EBCSO Academic Search Complete, Cochrane Systematic Reviews Database, and Google Scholar using key words; delayed ejaculation, retarded ejaculation, inhibited ejaculation, drugs, treatment, or pharmacology. To achieve the maximum sensitivity of the search strategy and to identify all studies, we combined "delayed ejaculation" as Medical Subject Headings (MeSH) terms or keywords with each of "testosterone" or "cabergoline" or "bupropion" or "amantadine" or "cyproheptadine" or "midodrine" or "imipramine" or "ephedrine" or "pseudoephedrine" or "yohimbine" or "buspirone" or "oxytocin" or "bethanechol" as MeSH terms or keywords. There are a number of drugs to treat patients with DE including: testosterone, cabergoline, bupropion, amantadine, cyproheptadine, midodrine, imipramine, ephedrine, pseudoephedrine, yohimbine, buspirone, oxytocin, and bethanechol. Although there are many pharmacological treatment options, the evidence is still limited to small trials, case series or case reports. Review of literature showed that evidence level 1 (Double blind randomized clinical trial) studies were performed with testosterone, oxytocin, buspirone or bethanechol treatment. It is concluded that successful drug treatment of DE is still in its infancy. The clinicians need to be aware of the pathogenesis of DE and the pharmacological basis underlying the use of different drugs to extend better care for these patients. Various drugs are available to address such problem, however their evidence of efficacy is still limited and their choice needs to be individualized to each specific case

  11. Testing Homeopathy in Mouse Emotional Response Models: Pooled Data Analysis of Two Series of Studies

    OpenAIRE

    Maria Elisabetta Zanolin; Mirko Cristofoletti; Paolo Magnani; Marta Marzotto; Anita Conforti; Paolo Bellavite; Debora Olioso

    2012-01-01

    Two previous investigations were performed to assess the activity of Gelsemium sempervirens (Gelsemium s.) in mice, using emotional response models. These two series are pooled and analysed here. Gelsemium s. in various homeopathic centesimal dilutions/dynamizations (4C, 5C, 7C, 9C, and 30C), a placebo (solvent vehicle), and the reference drugs diazepam (1 mg/kg body weight) or buspirone (5 mg/kg body weight) were delivered intraperitoneally to groups of albino CD1 mice, and their effects on ...

  12. Drug action at the 5-HT{sub 1A} receptor in vivo: autoreceptor and postsynaptic receptor occupancy examined with PET and [carbonyl-{sup 11}C]WAY-100635

    Energy Technology Data Exchange (ETDEWEB)

    Rabiner, Eugenii A. E-mail: ilan@cu.rpms.ac.uk; Gunn, Roger N.; Wilkins, Martin R.; Sargent, Peter A.; Mocaer, Elizabeth; Sedman, Ewen; Cowen, Philip J.; Grasby, Paul M

    2000-07-01

    Serotonin{sub 1A} (5-HT{sub 1A}) receptors have been implicated in the pathophysiology and treatment of anxiety and depression and are a target for novel drug development. In this qualitative study, positron emission tomography (PET) and [carbonyl-{sup 11}C]WAY-100635 were used to assess 5-HT{sub 1A} autoreceptor and postsynaptic receptor occupancy in man in vivo by five different compounds with nanomolar affinity for this site. Occupancy by pindolol, penbutolol, buspirone, EMD 68843, and S 15535 was compared to test-retest data from 10 healthy volunteers. All drugs, apart from buspirone, displayed occupancy at the 5-HT{sub 1A} receptor site. Pindolol demonstrated a preferential occupancy at the autoreceptor compared to the postsynaptic receptor over a plasma range of about 10-20 ng/mL. Differential occupancy may be an important component of novel drug action. The level of autoreceptor or postsynaptic occupancy needed to achieve significant physiological effects is not known, although it is of note that none of the drugs in this study achieved occupancies beyond 60%. Overall this study demonstrates the utility of PET in aiding novel drug development.

  13. The side-by-side exploratory test: a simple automated protocol for the evaluation of adult zebrafish behavior simultaneously with social interaction.

    Science.gov (United States)

    Schaefer, Isabel C; Siebel, Anna M; Piato, Angelo L; Bonan, Carla D; Vianna, Mônica R; Lara, Diogo R

    2015-10-01

    The assessment of shoaling in adult zebrafish is technically difficult, but important, given their social nature. The present study aimed to characterize a new protocol using simple automated tracking software to evaluate general behavior and social interaction simultaneously. To this end, we used a single tank with a central transparent glass division and placed one zebrafish on each side for 5 min. This strategy allows fish to interact visually at the same time that individual automated evaluation of behavior can be easily performed. Our results showed that, when two fish are placed side-by-side, there is an increase in their height in the tank compared with isolated fish and they remain close to each other. The pharmacological treatments with benzodiazepines (bromazepam and clonazepam) and the serotonergic drugs buspirone, fluoxetine, and escitalopram did not affect locomotion at the concentrations tested, except for the highest concentration of buspirone. Nevertheless, benzodiazepines increased interfish distance (i.e. reduced shoaling behavior) and serotonergic drugs elevated height in the tank. These results support the use of the side-by-side exploratory test for behavioral studies with the zebrafish, including high-throughput behavioral screening for antidepressants and anxiolytics. PMID:26061352

  14. Reprint of "Pharmacological study of the light/dark preference test in zebrafish (Danio rerio): Waterborne administration".

    Science.gov (United States)

    Magno, Lílian Danielle Paiva; Fontes, Aldo; Gonçalves, Beatriz Maria Necy; Gouveia, Amauri

    2015-12-01

    Anxiety is a complex disorder; thus, its mechanisms remain unclear. Zebrafish (Danio rerio) are a promising pharmacological model for anxiety research. Light/dark preference test is a behaviorally validated measure of anxiety in zebrafish; however, it requires pharmacological validation. We sought to evaluate the sensitivity of the light/dark preference test in adult zebrafish by immersing them in drug solutions containing clonazepam, buspirone, imipramine, fluoxetine, paroxetine, haloperidol, risperidone, propranolol, or ethanol. The time spent in the dark environment, the latency time to first crossing, and the number of midline crossings were analyzed. Intermediate concentrations of clonazepam administered for 600s decreased the time spent in the dark and increased locomotor activity. Buspirone reduced motor activity. Imipramine and fluoxetine increased time spent in the dark and the first latency, and decreased the number of alternations. Paroxetine did not alter the time in the dark; however, it increased the first latency time and decreased locomotor activity. Haloperidol decreased the time spent in the dark at low concentrations. Risperidone and propranolol did not change any parameters. Ethanol reduced the time spent in the dark and increased the number of crossings at intermediate concentrations. These results corroborate the previous work using intraperitoneal drug administration in zebrafish and rodents, suggesting that water drug delivery in zebrafish can effectively be used as an animal anxiety model. PMID:26569548

  15. Pharmacological study of the light/dark preference test in zebrafish (Danio rerio): Waterborne administration.

    Science.gov (United States)

    Magno, Lílian Danielle Paiva; Fontes, Aldo; Gonçalves, Beatriz Maria Necy; Gouveia, Amauri

    2015-08-01

    Anxiety is a complex disorder; thus, its mechanisms remain unclear. Zebrafish (Danio rerio) are a promising pharmacological model for anxiety research. Light/dark preference test is a behaviorally validated measure of anxiety in zebrafish; however, it requires pharmacological validation. We sought to evaluate the sensitivity of the light/dark preference test in adult zebrafish by immersing them in drug solutions containing clonazepam, buspirone, imipramine, fluoxetine, paroxetine, haloperidol, risperidone, propranolol, or ethanol. The time spent in the dark environment, the latency time to first crossing, and the number of midline crossings were analyzed. Intermediate concentrations of clonazepam administered for 600s decreased the time spent in the dark and increased locomotor activity. Buspirone reduced motor activity. Imipramine and fluoxetine increased time spent in the dark and the first latency, and decreased the number of alternations. Paroxetine did not alter the time in the dark; however, it increased the first latency time and decreased locomotor activity. Haloperidol decreased the time spent in the dark at low concentrations. Risperidone and propranolol did not change any parameters. Ethanol reduced the time spent in the dark and increased the number of crossings at intermediate concentrations. These results corroborate the previous work using intraperitoneal drug administration in zebrafish and rodents, suggesting that water drug delivery in zebrafish can effectively be used as an animal anxiety model. PMID:26026898

  16. Various functions of PBMC from colon cancer patients are not decreased compared to healthy blood donors

    DEFF Research Database (Denmark)

    Afzelius, P; Nielsen, Hans Jørgen

    1997-01-01

    -2 and its receptor proteins in T helper cells. The proliferative responses and IL-2 synthesis of PBMC have earlier been shown to be reduced in patients with colon cancer. Recently immune modulating agents have been demonstrated to increase the proliferative response of PBMC in vitro, probably...... by inhibition of adenylate cyclase activity and induction of IL-2 mRNA expression. We have therefore studied the proliferative responses of PBMC from colon cancer patients to PWM and tested the effect of immune modulating agents, such as Serotonin, Sumatriptan, and Buspirone on these PBMC. We found...... no difference in levels of intracellular cAMP, IL-2 mRNA expression, IL-2R mRNA expression, or proliferative responses of PBMC from colon cancer patients compared to healthy blood donors. There was no effect of the immune modulating agents on PBMC from colon cancer patients....

  17. Developing strategies for isolation of minor impurities with mass spectrometry-directed fractionation.

    Science.gov (United States)

    Niessen, Wilfried M A; Lin, Jing; Bondoux, Gérard C

    2002-09-13

    Efficient and automated purification of new chemical entities/potential drug substances and isolation of minor impurities are important aspects of early drug discovery and development strategies, especially when combinatorial synthesis is applied. LC-MS controlled preparative LC and automated fraction collection have been developed for this purpose. The success of such an approach is greatly determined by the quality of the software controlling the application, the coordination between software and hardware, and the reliability of the hardware. The performance of a commercially-available LC-MS controlled autopurification system was evaluated by fractionating four impurities of buspirone as a model compound, eluting closely to the major component under both acidic and basic mobile-phase conditions. A purification strategy for these four components is proposed.

  18. EuroHYP-1

    DEFF Research Database (Denmark)

    van der Worp, H Bart; Macleod, Malcolm R; Bath, Philip M W;

    2014-01-01

    shown feasible in phase II clinical trials. PRIMARY AIM: To determine whether systemic cooling to a target body temperature between 34·0 and 35·0°C, started within six-hours of symptom onset and maintained for 24 h, improves functional outcome at three-months in patients with acute ischemic stroke....... DESIGN: International, multicenter, phase III, randomized, open-label clinical trial with blinded outcome assessment in 1500 patients aged 18 years or older with acute ischemic stroke and a National Institutes of Health Stroke Scale score of 6 up to and including 18. In patients randomized to hypothermia...... will receive pethidine and buspirone to prevent shivering and discomfort. PRIMARY OUTCOME: Score on the modified Rankin Scale at 91 days, as analyzed with ordinal logistic regression and expressed as a common odds ratio. DISCUSSION: With 750 patients per intervention group, this trial has 90% power to detect 7...

  19. Serotonin receptor subtype mediation of the interoceptive discriminative stimuli induced by 5-methoxy-N,N-dimethyltryptamine.

    Science.gov (United States)

    Spencer, D G; Glaser, T; Traber, J

    1987-01-01

    Male Wistar rats were trained to discriminate the interoceptive effects of 5-methoxy-N,N-dimethyltryptamine (5-OMe-DMT; 1.25 mg/kg, IP) from saline in a two-lever operant chamber. Following discrimination learning, the following drugs (with ED50 dose in mg/kg IP) dose-dependently generalized: lysergic acid diethylamide (LSD, 0.04), 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT, 0.11), 6-methoxy-4-(dipropyl-amino)-1,3,4,5-tetrahydrobenz(c,d)indole hydrochloride (BAY R 1531, 0.15), 5-OMe-DMT itself (0.63), ipsapirone (TVX Q 7821, 2.7), and buspirone (3.8). The potencies of these drugs in generalization tests were best correlated with their binding affinities for the 5-HT1A serotonin receptor subtype (as measured by displacement of 3H-ipsapirone in the hippocampus). Drugs not, or only partially generalizing included quipazine, bufotenin, m-trifluoromethylphenylpiperazine (TFMPP), 5-methoxy-3(1,2,3,6-tetrahydropyridine-4-yl)-1H-indole succinate (RU 24969), citalopram, clomipramine, 1,4-dihydro-2,6-dimethyl-3-nitro-4(2-trifluoromethylphenyl)-pyridine-5- carboxylate (BAY K 8644), the buspirone metabolite 1-pyrimidinyl-piperazine (1-PP), methysergide, metergoline, and metitepine. Of the last three compounds with antagonistic activity at 5-HT receptors, as well as ketanserin, pizotifen, and ritanserin, only metitepine and pindolol could fully block the 5-OMe-DMT stimulus. Pizotifen blocked the generalization of quipazine fully, that of 5-OMe-DMT only partially, and that of ipsapirone not at all. These data indicate that the 5-HT1A receptor subtype is strongly involved in the transduction of the interoceptive discriminative stimuli induced by 5-OMe-DMT, with 5-HT2 agonism also playing a possible role. PMID:3122248

  20. Depressão resistente a tratamento: uma revisão das estratégias farmacológicas de potencialização de antidepressivos Treatment-resistant depression: review of pharmacologic antidepressant strategies

    Directory of Open Access Journals (Sweden)

    Milena Antunes Santos

    2006-01-01

    , LILACS and Cochrane Library, from 1990 to June 2006 using the words treatment, resistant, refractory, depression and the medical subject headings depression, drug resistance and augmentation. Double-blind controlled trials and reviews were included. We also consulted reference of the articles in order to obtain studies and original articles of historical value from before 1990. RESULTS: There were 17 double-blind trials with lithium, six with thyroid hormone, two with buspirone, six with pindolol one with carbamazepine, two with lamotrigine and four with olanzapine. Forty-one percent of the trials with lithium, 60% of those with thyroid hormone and tricyclics, 0% of the ones with thyroid hormone and selective serotonin reuptake inhibitors (SSRI, 50% of those with pindolol, 100% of those with carbamazepine and 40% of the ones with olanzapine were favorable. No trials with buspirone were favorable. The only trial with lamotrigine did not show efficacy using the main outcome measures. Otherwise, there was superiority over placebo on secondary measures. CONCLUSION: Only lithium and thyroid hormone showed efficacy as antidepressant augmentation strategies for TRD. Olanzapine was reasonably studied and did not prove its efficacy. There were just a few studies on buspirone and pindolol and they were not favorable to them. Carbamazepine was studied very little. Lamotrigine was not adequately evaluated.

  1. The Psychopharmacology Algorithm Project at the Harvard South Shore Program: An Algorithm for Generalized Anxiety Disorder.

    Science.gov (United States)

    Abejuela, Harmony Raylen; Osser, David N

    2016-01-01

    This revision of previous algorithms for the pharmacotherapy of generalized anxiety disorder was developed by the Psychopharmacology Algorithm Project at the Harvard South Shore Program. Algorithms from 1999 and 2010 and associated references were reevaluated. Newer studies and reviews published from 2008-14 were obtained from PubMed and analyzed with a focus on their potential to justify changes in the recommendations. Exceptions to the main algorithm for special patient populations, such as women of childbearing potential, pregnant women, the elderly, and those with common medical and psychiatric comorbidities, were considered. Selective serotonin reuptake inhibitors (SSRIs) are still the basic first-line medication. Early alternatives include duloxetine, buspirone, hydroxyzine, pregabalin, or bupropion, in that order. If response is inadequate, then the second recommendation is to try a different SSRI. Additional alternatives now include benzodiazepines, venlafaxine, kava, and agomelatine. If the response to the second SSRI is unsatisfactory, then the recommendation is to try a serotonin-norepinephrine reuptake inhibitor (SNRI). Other alternatives to SSRIs and SNRIs for treatment-resistant or treatment-intolerant patients include tricyclic antidepressants, second-generation antipsychotics, and valproate. This revision of the GAD algorithm responds to issues raised by new treatments under development (such as pregabalin) and organizes the evidence systematically for practical clinical application.

  2. Modulation of hepatic cytochrome p450 enzymes by curcumin and its pharmacokinetic consequences in sprague-dawley rats

    Directory of Open Access Journals (Sweden)

    Sang-Bum Kim

    2015-01-01

    Full Text Available Background: Curcumin (CUR is a polyphenolic component derived from an herbal remedy and dietary spice turmeric (Curcuma longa. Objective: The aim of this study was to investigate inhibitory effects of CUR on in vitro cytochrome P450 (CYP activity and in vivo pharmacokinetic consequences of single CUR dose in rats. Materials and Methods: An in vitro CYP inhibition study in rat liver microsomes (RLM was conducted using probe substrates for CYPs. Then, an in vivo pharmacokinetics of intravenous buspirone (BUS, a probe substrate for CYP3A, was studied with the concurrent administration of oral CUR in rats. Results: In the in vitro CYP inhibition study, CUR inhibited the CYP3A-mediated metabolism of testosterone (TES with a half maximal inhibitory concentration of 11.0 ΁ 3.3 mM. However, the impact of a single oral CUR dose on the pharmacokinetics of BUS in rats is limited, showing that CUR cannot function as an inhibitor for CYP3A-mediated drug metabolism in vivo. Conclusion: To the best of our knowledge, our results are the first reported data regarding the inhibition of in vitro CYP3A-mediated metabolism of TES and the in vivo impact of a single CUR dose on the pharmacokinetics of BUS in rats. Further study is required to draw a confirmative conclusion on whether CUR can be a clinically relevant CYP3A4 inhibitor.

  3. Obsessive-compulsive disorder.

    Science.gov (United States)

    Bokor, Gyula; Anderson, Peter D

    2014-04-01

    Obsessive-compulsive disorder (OCD) is a common heterogeneous psychiatric disorder manifesting with obsessions and compulsions. Obsessions are intrusive, recurrent, and persistent unwanted thoughts. Compulsions are repetitive behaviors or mental acts that an individual feels driven to perform in response to the obsessions. The heterogeneity of OCD includes themes of obsessions, types of rituals, presence or absence of tics, etiology, genetics, and response to pharmacotherapy. Complications of OCD include interpersonal difficulties, unemployment, substance abuse, criminal justice issues, and physical injuries. Areas of the brain involved in the pathophysiology include the orbitofrontal cortex, anterior cingulate gyrus, and basal ganglia. Overall, OCD may be due to a malfunction in the cortico-striato-thalamo-cortical circuit in the brain. Neurotransmitters implicated in OCD include serotonin, dopamine, and glutamate. Numerous drugs such as atypical antipsychotics and dopaminergic agents can cause or exacerbate OCD symptoms. The etiology includes genetics and neurological insults. Treatment of OCD includes psychotherapy, pharmacotherapy, electroconvulsive therapy, transcranial magnetic simulation, and in extreme cases surgery. Exposure and response prevention is the most effective form of psychotherapy. Selective serotonin reuptake inhibitors (SSRIs) are the preferred pharmacotherapy. Higher doses than listed in the package insert and a longer trial are often needed for SSRIs than compared to other psychiatric disorders. Alternatives to SSRIs include clomipramine and serotonin/norepinephrine reuptake inhibitors. Treatment of resistant cases includes augmentation with atypical antipsychotics, pindolol, buspirone, and glutamate-blocking agents. PMID:24576790

  4. Color Preference in Danio rerio: Effects of Age and Anxiolytic Treatments.

    Science.gov (United States)

    Peeters, Bernardus W M M; Moeskops, Max; Veenvliet, Anne R J

    2016-08-01

    Zebrafish are increasingly used in neurobiological and behavioral studies. Possible stimuli to manipulate zebrafish behavior are being investigated. The presentation of colors appears to be one of the most used approaches, but there is much debate about the exact color preference. Here we have investigated the color preference in both larvae and adult zebrafish. We have studied the effects of wavelength, contrast, intensity, and location. Furthermore, we have tried to manipulate the preference with anxiolytic drugs (ethanol and buspirone). Our results show that both adults and larvae have a clear preference for blue zones while they avoid yellow-colored zones. Red and green zones have an intermediate preference. Part of the yellow aversion is caused by a fear for this color and can be diminished by the treatment with anxiolytic drugs. The location of the color appears to be of critical importance. Presentation of the color on the walls induces an approach response whereas presentation on the bottom induces an aversion. In conclusion, colors are important stimuli to manipulate zebrafish behavior and can be used in behavioral models. Standardization of the procedures and a clear description of the used methodologies are, however, essential.

  5. Tratamento farmacológico do transtorno de ansiedade generalizada: perspectivas futuras Pharmacological treatment of generalized anxiety disorder: future perspectives

    Directory of Open Access Journals (Sweden)

    Roberto Andreatini

    2001-12-01

    Full Text Available O presente artigo apresenta uma visão atualizada e ampla do tratamento farmacológico do transtorno de ansiedade generalizada (TAG. São revistos os medicamentos com eficácia comprovada em estudos controlados e atualmente disponíveis na clínica (benzodiazepínicos, buspirona, antidepressivos, betabloqueadores, antipsicóticos e extrato de kava-kava. A seguir, baseados nesses dados, propõe-se um algoritmo de tratamento do TAG. São apresentadas as principais linhas de pesquisa de novos fármacos ansiolíticos, descrevendo os principais achados clínicos e pré-clínicos.This article presents an updated and broad perspective of the pharmacological treatment of generalized anxiety disorder (GAD. Medications proven to be efficacious in controlled studies and available in the clinic setting were reviewed (benzodiazepines, buspirone, antidepressives, beta-blocking agents, antipsychotics and kava-kava extract. From this data, an algorithm for GAD treatment is proposed. In addition, the main research lines on new anxiolytic drugs and their stage of clinical or pre-clinical development are presented.

  6. Modifying 5-HT1A receptor gene expression as a new target for antidepressant therapy

    Directory of Open Access Journals (Sweden)

    Paul R Albert

    2010-06-01

    Full Text Available Major depression is the most common form of mental illness, and is treated with antidepressant compounds that increase serotonin (5-HT neurotransmission. Increased 5-HT1A autoreceptor levels in the raphe nuclei act as a “brake” to inhibit the 5-HT system, leading to depression and resistance to antidepressants. Several 5-HT1A receptor agonists (buspirone, flesinoxan, ipsapirone that preferentially desensitize 5-HT1A autoreceptors have been tested for augmentation of antidepressant drugs with mixed results. One explanation could be the presence of the C(-1019G 5-HT1A promoter polymorphism that prevents gene repression of the 5-HT1A autoreceptor. Furthermore, down-regulation of 5-HT1A autoreceptor expression, not simply desensitization of receptor signaling, appears to be required to enhance and accelerate antidepressant action. The current review focuses on the transcriptional regulators of 5-HT1A autoreceptor expression, their roles in permitting response to 5-HT1A-targeted treatments and their potential as targets for new antidepressant compounds for treatment-resistant depression.

  7. Foetal Cell Transplantation for Parkinson’s Disease: Focus on Graft-Induced Dyskinesia

    Directory of Open Access Journals (Sweden)

    Elisabetta Tronci

    2015-01-01

    Full Text Available Transplantation of dopamine- (DA- rich foetal ventral mesencephalic cells emerged as a promising therapy for Parkinson’s disease (PD, as it allowed significant improvement of motor symptoms in several PD patients in open-label studies. However, double-blind clinical trials have been largely disappointing. The general agreement in the field is that the lack of standardization of tissue collection and preparation, together with the absence of postsurgical immunosuppression, played a key role in the failure of these studies. Moreover, a further complication that emerged in previous studies is the appearance of the so-called graft-induced dyskinesia (GID, in a subset of grafted patients, which resembles dyskinesia induced by L-DOPA but in the absence of medication. Preclinical evidence pointed to the serotonin neurons as possible players in the appearance of GID. In agreement, clinical investigations have shown that grafted tissue may contain a large number of serotonin neurons, in the order of half of the DA cells; moreover, the serotonin 5-HT1A receptor agonist buspirone has been found to produce significant dampening of GID in grafted patients. In this paper, we will review the recent preclinical and clinical studies focusing on cell transplantation for PD and on the mechanisms underlying GID.

  8. Testing Homeopathy in Mouse Emotional Response Models: Pooled Data Analysis of Two Series of Studies

    Directory of Open Access Journals (Sweden)

    Paolo Bellavite

    2012-01-01

    Full Text Available Two previous investigations were performed to assess the activity of Gelsemium sempervirens (Gelsemium s. in mice, using emotional response models. These two series are pooled and analysed here. Gelsemium s. in various homeopathic centesimal dilutions/dynamizations (4C, 5C, 7C, 9C, and 30C, a placebo (solvent vehicle, and the reference drugs diazepam (1 mg/kg body weight or buspirone (5 mg/kg body weight were delivered intraperitoneally to groups of albino CD1 mice, and their effects on animal behaviour were assessed by the light-dark (LD choice test and the open-field (OF exploration test. Up to 14 separate replications were carried out in fully blind and randomised conditions. Pooled analysis demonstrated highly significant effects of Gelsemium s. 5C, 7C, and 30C on the OF parameter “time spent in central area” and of Gelsemium s. 5C, 9C, and 30C on the LD parameters “time spent in lit area” and “number of light-dark transitions,” without any sedative action or adverse effects on locomotion. This pooled data analysis confirms and reinforces the evidence that Gelsemium s. regulates emotional responses and behaviour of laboratory mice in a nonlinear fashion with dilution/dynamization.

  9. Effects of 5-HT1A receptor agonists and NMDA receptor antagonists in the social interaction test and the elevated plus maze.

    Science.gov (United States)

    Dunn, R W; Corbett, R; Fielding, S

    1989-10-01

    The effects of several 5-HT1A agonists and excitatory amino acid antagonists were compared to the standard benzodiazepines, diazepam and chlordiazepoxide (CDP) in two assays predictive of anxiolytic activity, the social interaction and elevated plus maze procedures. Indicative of anxiolytic effects the 5-HT1A agonists, buspirone, gepirone and 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) all significantly increased social interaction time and open arm exploration time in the social interaction and elevated plus maze procedures, respectively. Likewise, anxiolytic activity in these assays were also produced by the competitive N-methyl-D-aspartate (NMDA) antagonists, 2-amino-5-phosphonovaleric acid (AP-5), 2-amino-7-phosphonoheptanoic acid (AP-7), 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) and the non-competitive NMDA antagonist, (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801) while NMDA produced anxiogenic effects. Furthermore, the anxiolytic effects of these agents were of equal magnitude to the benzodiazepines. These two classes of compounds were differentiated in the yohimbine-induced seizure assay, with the NMDA antagonists dose dependently antagonizing seizures similar to the benzodiazepines while the 5-HT1A agonists were inactive. These results suggest that the 5-HT1A agonists and the NMDA antagonists may be potential non-classical anxiolytic agents with different mechanisms of action.

  10. Comparison of TiO2 photocatalysis, electrochemically assisted Fenton reaction and direct electrochemistry for simulation of phase I metabolism reactions of drugs.

    Science.gov (United States)

    Ruokolainen, Miina; Gul, Turan; Permentier, Hjalmar; Sikanen, Tiina; Kostiainen, Risto; Kotiaho, Tapio

    2016-02-15

    The feasibility of titanium dioxide (TiO2) photocatalysis, electrochemically assisted Fenton reaction (EC-Fenton) and direct electrochemical oxidation (EC) for simulation of phase I metabolism of drugs was studied by comparing the reaction products of buspirone, promazine, testosterone and 7-ethoxycoumarin with phase I metabolites of the same compounds produced in vitro by human liver microsomes (HLM). Reaction products were analysed by UHPLC-MS. TiO2 photocatalysis simulated the in vitro phase I metabolism in HLM more comprehensively than did EC-Fenton or EC. Even though TiO2 photocatalysis, EC-Fenton and EC do not allow comprehensive prediction of phase I metabolism, all three methods produce several important metabolites without the need for demanding purification steps to remove the biological matrix. Importantly, TiO2 photocatalysis produces aliphatic and aromatic hydroxylation products where direct EC fails. Furthermore, TiO2 photocatalysis is an extremely rapid, simple and inexpensive way to generate oxidation products in a clean matrix and the reaction can be simply initiated and quenched by switching the UV lamp on/off.

  11. Anxiolytic-like effects of leptin on fixed interval responding.

    Science.gov (United States)

    Tyree, Susan M; Munn, Robert G K; McNaughton, Neil

    2016-09-01

    Leptin has been shown to affect energy homeostasis, learning and memory, and some models of anxiolytic action. However, leptin has produced inconsistent results in previous non-operant behavioural tests of anxiety. Here, we test the anxiolytic potential of leptin in an operant paradigm that has produced positive results across all classes of anxiolytic so far tested. Rats were tested in the Fixed Interval 60 Seconds (FI60) task following administration of 0/0.5/1.0mg/kg (i.p.) leptin or an active anxiolytic control of 5mg/kg (i.p.) chlordiazepoxide (CDP). By the end of the 14days of testing in the FI60 task, 0.5mg/kg leptin released suppressed responding in a manner similar to CDP, and 1.0mg/kg leptin produced a relative depression in responding, a similar outcome pattern to previously tested 5HT-agonist anxiolytics. This suggests that leptin behaves similarly to established serotonergic anxiolytics such as buspirone and fluoxetine; with the delay in development of effect during testing, and the inverted-U dose-response curve explaining the inconsistent behaviour of leptin in behavioural tests of anxiety, as this type of pattern is common to serotonergic anxiolytics. PMID:27180106

  12. Gepirone. Organon.

    Science.gov (United States)

    Leslie, R A

    2001-08-01

    Gepirone, a pyridinyl piperazine 5-HT1A receptor agonist, has been developed by Fabre-Kramer as an antidepressant. Bristol-Myers Squibb (BMS) outlicensed the compound to Fabre-Kramer in 1993 and is no longer involved in its development [337393]. In May 1998, NV Organon (a subsidiary of Akzo Nobel) licensed the rights to the drug product for further development and marketing from Fabre-Kramer and, by October 1999, had submitted the drug for approval in the US [347133]. In December 2000, the company expected US and European launches in 2002 and 2003, respectively [402686]. Mechanism of action studies have demonstrated that gepirone, compared to buspirone, possesses a much greater selectivity for 5-HT1A receptors over dopamine D2 receptors. Long-term studies have shown that gepirone has a differential action at presynaptic (agonist) and post-synaptic (partial agonist) 5-HT1A receptors. However, further studies are still required to determine the relative contribution of pre- and post-synaptic 5-HT1A receptors to the therapeutic action of gepirone and related compounds. In March 2001, according to Schroder Salomon Smith Barney, Akzo Nobel targeted peak sales of Euro 300 million for gepirone [409013]. This amount was reiterated in an April 2001 report by HSBC Securities, which stated that gepirone was expected to achieve this figure in 2009 or 2010 [409014].

  13. Assessment of Antishivering Medication Requirements During Therapeutic Normothermia: Effect of Cooling Methods.

    Science.gov (United States)

    Kirk, Andrew; McDaniel, Cara; Szarlej, Dorota; Rincon, Fred

    2016-08-01

    Shivering during targeted temperature management (TTM) should be minimized because it can cause cerebral and metabolic stress. It has been proposed that surface cooling (SC) may result in more shivering than endovascular cooling (EC) methods. The purpose of this study was to compare antishivering medication requirements and degree of shivering in these groups during TTM to Normothermia (NT). This was a retrospective single-center cohort study of patients treated with protocolized TTM through SC and EC methods to achieve NT (37.0-37.5°C). The number of interventions and daily dose of antishivering medications, per institutional protocol, were compared between the two groups. The intensity of shivering was assessed with the Bedside Shivering Assessment Scale. Patients in the EC group (n = 23) had more antishivering interventions per patient day than those in the SC group (n = 43) (3.28 vs. 2.67, p = 0.002). Acetaminophen (81% vs. 59%, p shivering. In our cohort, patients in EC group required more antishivering interventions, but less sedation, during TTM than patients in SC group. Optimizing nonsedating medications, such as acetaminophen, buspirone, and magnesium infusions, may decrease the requirement for sedatives to control shivering in both SC and EC. PMID:26990844

  14. The Psychopharmacology Algorithm Project at the Harvard South Shore Program: An Algorithm for Generalized Anxiety Disorder.

    Science.gov (United States)

    Abejuela, Harmony Raylen; Osser, David N

    2016-01-01

    This revision of previous algorithms for the pharmacotherapy of generalized anxiety disorder was developed by the Psychopharmacology Algorithm Project at the Harvard South Shore Program. Algorithms from 1999 and 2010 and associated references were reevaluated. Newer studies and reviews published from 2008-14 were obtained from PubMed and analyzed with a focus on their potential to justify changes in the recommendations. Exceptions to the main algorithm for special patient populations, such as women of childbearing potential, pregnant women, the elderly, and those with common medical and psychiatric comorbidities, were considered. Selective serotonin reuptake inhibitors (SSRIs) are still the basic first-line medication. Early alternatives include duloxetine, buspirone, hydroxyzine, pregabalin, or bupropion, in that order. If response is inadequate, then the second recommendation is to try a different SSRI. Additional alternatives now include benzodiazepines, venlafaxine, kava, and agomelatine. If the response to the second SSRI is unsatisfactory, then the recommendation is to try a serotonin-norepinephrine reuptake inhibitor (SNRI). Other alternatives to SSRIs and SNRIs for treatment-resistant or treatment-intolerant patients include tricyclic antidepressants, second-generation antipsychotics, and valproate. This revision of the GAD algorithm responds to issues raised by new treatments under development (such as pregabalin) and organizes the evidence systematically for practical clinical application. PMID:27384395

  15. Effect of anti-anxiety and depression drugs on metabolic control of type Ⅱ diabetes patients complicated with anxiety and depression%抗焦虑抑郁药物对Ⅱ型糖尿病合并焦虑抑郁状态代谢控制的影响

    Institute of Scientific and Technical Information of China (English)

    黄令一; 李爱平; 伍丽霞

    2012-01-01

    目的 观察和评价抗焦虑抑郁药物对Ⅱ型糖尿病合并焦虑抑郁状态代谢控制的影响.方法 将60例Ⅱ型糖尿病人随机分为观察组和对照组各30例,治疗12周为1个疗程.观察组采用氯丙咪嗪、丁螺环酮、阿普唑伦治疗;对照组采用丁螺环酮、百乐眠胶囊治疗.结果 治疗12周后两组焦虑抑郁评分与治疗前比较均有明显改善,治疗组效果更明显,两组比较差异有统计学意义(P<0.05);治疗12周后,空腹血糖、餐后2h血糖、糖化血红蛋白、甘油三脂均有明显下降,治疗组下降更明显,两组比较差异有统计学意义(P<0.05).结论 抗焦虑抑郁药物可以改善Ⅱ型糖尿病人的焦虑抑郁状态,降低空腹血糖、餐后2h血糖、血脂及糖化血红蛋白.%Objective To observe and evaluate the effect of anti-anxiety and depression drugs on metabolic control of type II diabetes patients complicated with anxiety and depression. Methods Totally 40 patients with type II diabetes from 2009 to 2010 were enrolled and randomly divided into control group and treatment group (n = 20). Twelve weeks was considered for one course of the treatment. The patients in treatment group were treated with Clornipramine, Buspi-rone and Alprazolam while those in control group were treated by Buspirone and Paramount sleep capsule. Results Obvious improvement of anxiety and depression in the two groups were observed after 12 weeks of treatment according to the anxiety and depression scores. The improvement in treatment group was more obvious than that in control group, with statistical differences (P<0. 05). The fasting glucose,postprandial 2 h blood glucose, glycated hemoglobin, triglycerides were significantly reduced after 12 weeks of treatment, with more significant decreases in treatment group compared with those in control group (P<0. 05). Conclusion Anti-anxiety and depression drugs can improve depression status of patients with type II diabetes

  16. iPhone® applications as versatile video tracking tools to analyze behavior in zebrafish (Danio rerio).

    Science.gov (United States)

    Pittman, Julian T; Ichikawa, Katie M

    2013-05-01

    Zebrafish (Danio rerio) are emerging as a promising model organism for experimental studies relevant to biological psychiatry. The objective of this study was to develop a novel video-based movement tracking and analysis system to quantify behavioral changes following psychoactive drug exposure in zebrafish. We assessed the effects of withdrawal from chronic ethanol exposure, and subsequent administration of fluoxetine (Prozac®), buspirone (Buspar®), and diazepam (Valium) using two behavioral paradigms; the Novel Tank Diving Test and the Light/Dark Choice Assay. A video tracking system was developed using two Apple® applications (Apps) to quantify these behaviors. Data from zebrafish exposed to the above treatments are presented in this paper not only to exemplify behavioral alterations associated with chronic exposure, but also more importantly, to validate the video tracking system. Following withdrawal from chronic ethanol exposure, zebrafish exhibited dose/time-dependent anxiogenic effects; including reduced exploration and freezing behavior in the Novel Tank Diving Test, and preference for the dark area for the Light/Dark Choice Assay. In contrast, the above drug treatments had significant anxiolytic effects. We have developed a simple and cost-effective method of measuring zebrafish behavioral responses. The iPhone® Apps outlined in this study offer numerous flexible methods of data acquisition; namely, ease of identification and tracking of multiple animals, tools for visualization of the tracks, and calculation of a range of analysis parameters. Furthermore, the limited amount of time required for interpretation of the video data makes this a powerful high-throughput tool with potential applications for pre-clinical drug development. PMID:23558086

  17. Application of a cocktail approach to screen cytochrome P450 BM3 libraries for metabolic activity and diversity.

    Science.gov (United States)

    Reinen, Jelle; Postma, Geert; Tump, Cornelis; Bloemberg, Tom; Engel, Jasper; Vermeulen, Nico P E; Commandeur, Jan N M; Honing, Maarten

    2016-02-01

    In the present study, the validity of using a cocktail screening method in combination with a chemometrical data mining approach to evaluate metabolic activity and diversity of drug-metabolizing bacterial Cytochrome P450 (CYP) BM3 mutants was investigated. In addition, the concept of utilizing an in-house-developed library of CYP BM3 mutants as a unique biocatalytic synthetic tool to support medicinal chemistry was evaluated. Metabolic efficiency of the mutant library towards a selection of CYP model substrates, being amitriptyline (AMI), buspirone (BUS), coumarine (COU), dextromethorphan (DEX), diclofenac (DIC) and norethisterone (NET), was investigated. First, metabolic activity of a selection of CYP BM3 mutants was screened against AMI and BUS. Subsequently, for a single CYP BM3 mutant, the effect of co-administration of multiple drugs on the metabolic activity and diversity towards AMI and BUS was investigated. Finally, a cocktail of AMI, BUS, COU, DEX, DIC and NET was screened against the whole in-house CYP BM3 library. Different validated quantitative and qualitative (U)HPLC-MS/MS-based analytical methods were applied to screen for substrate depletion and targeted product formation, followed by a more in-depth screen for metabolic diversity. A chemometrical approach was used to mine all data to search for unique metabolic properties of the mutants and allow classification of the mutants. The latter would open the possibility of obtaining a more in-depth mechanistic understanding of the metabolites. The presented method is the first MS-based method to screen CYP BM3 mutant libraries for diversity in combination with a chemometrical approach to interpret results and visualize differences between the tested mutants. PMID:26753974

  18. Pharmacological targeting of dopamine D3 receptors: Possible clinical applications of selective drugs.

    Science.gov (United States)

    Pich, Emilio Merlo; Collo, Ginetta

    2015-09-01

    Dopamine D3 receptors have been pharmacologically engaged in humans since the development of the first antipsychotics and ergot-derivative dopamine (DA) agonists, even without knowing it. These agents were generally non-selective, developed primarily to target D2 receptors. In the last 10 years the understanding of the clinical implication of D3 receptors has been progressing also due to the identification of D3 gene polymorphisms, the use of more selective PET ligands such as [(11)C]-(+)-PHNO and the learning regarding the clinical use of the D3-preferential D2/D3 agonists ropinirole and pramipexole. A new specific neuroplasticity role of D3 receptor regarding dendrite arborisation outgrowth in dopaminergic neurons was also proposed to support, at least in part, the slowing of disease observed in subjects with Parkinson׳s Disease treated with DA agonists. Similar mechanisms could be at the basis of the antidepressant-like effects observed with DA agonists when co-administered with standard of care. Severe adverse event occurring with the use of anti-parkinsonian DA agonists in predisposed subjects, i.e., impulse control disorders, are now suggested to be putatively related to overactive D3 receptors. Not surprisingly, blockade of D3 receptors was proposed as treatment for addictive disorders, a goal that could be potentially achieved by repositioning buspirone, an anxiolytic drug with D3-preferential antagonistic features, or with novel selective D3 antagonists or partial agonists currently in development for schizophrenia. At the moment ABT-925 is the only selective D3 antagonist tested in schizophrenic patients in Phase II, showing an intriguing cognitive enhancing effects supported by preclinical data. Finally, exploratory pharmacogenetic analysis suggested that ABT-925 could be effective in a subpopulation of patients with a polymorphism on the D3 receptor, opening to a possible personalised medicine approach. PMID:26298833

  19. New trends in the treatment of nicotine addiction.

    Science.gov (United States)

    Sliwińska-Mossoń, Mariola; Zieleń, Iwona; Milnerowicz, Halina

    2014-01-01

    The aim of this study was to discuss the therapeutic substances used to treat nicotine addiction, not registered in Poland. This paper presents the results of the latest clinical trials and the possibility of their use in the treatment of nicotine addiction. The first two discussed drugs clonidine and nortriptyline are recommended by clinical practice guidelines AHRQ (Agency for Healthcare Research and Quality) as the substance of the second line in the fight against addiction. Nortriptyline belongs to tricyclic antidepressants. Its mechanism of action is the inhibition of the reuptake of norepinephrine. It is suggested as the antagonist of activity of nicotinic receptors. The results confirm its efficacy in the treatment of nicotine addiction, but many side effects limit its use. Clonidine acts presumably by inhibition of sympathetic hyperactivity characteristic of symptoms associated with nicotine rehab. The remaining compounds under discussion, such as: venlafaxine, fluoxetine, moclobemide and rimonabant, are not registered in any country with an indication to use in the treatment of nicotine addiction, however, due to the mechanism in which they act, the possibility of their use in the treatment of this disease is considered. The possibility of using anxiolytics such as: buspirone, diazepam, meprobamate and beta-blockers: metoprolol and oxprenolol is also considered in order to treat the anxiety appearing as one of the symptoms of abstinence. An interesting proposal to combat nicotine addiction are vaccines--NicVAX, CYT002-NicQb and TA-NIC. Currently, they are in clinical phase I and II of their development. Their operation would be based on the induction of specific antibodies that bind nicotine in the plasma, thus prevent it reaching the nicotinic receptors. Preliminary results confirm the possible positive effects in the prevention and treatment of nicotine addiction. PMID:25272878

  20. Novel Pharmacologic Approaches to Treating Cannabis Use Disorder.

    Science.gov (United States)

    Balter, Rebecca E; Cooper, Ziva D; Haney, Margaret

    2014-06-01

    With large and increasing numbers of people using cannabis, the development of cannabis use disorder (CUD) is a growing public health concern. Despite the success of evidence-based psychosocial therapies, low rates of initial abstinence and high rates of relapse during and following treatment for CUD suggest a need for adjunct pharmacotherapies. Here we review the literature on medication development for the treatment of CUD, with a particular focus on studies published within the last three years (2010-2013). Studies in both the human laboratory and in the clinic have tested medications with a wide variety of mechanisms. In the laboratory, the following medication strategies have been shown to decrease cannabis withdrawal and self-administration following a period of abstinence (a model of relapse): the cannabinoid receptor agonist, nabilone, and the adrenergic agonist, lofexidine, alone and in combination with dronabinol (synthetic THC), supporting clinical testing of these medication strategies. Antidepressant, anxiolytic and antipsychotic drugs targeting monoamines (norepinephrine, dopamine, and serotonin) have generally failed to decrease withdrawal symptoms or laboratory measures of relapse. In terms of clinical trials, dronabinol and multiple antidepressants (fluoxetine, venlafaxine and buspirone) have failed to decrease cannabis use. Preliminary results from controlled clinical trials with gabapentin and N-acetylcysteine (NAC) support further research on these medication strategies. Data from open label and laboratory studies suggest lithium and oxytocin also warrant further testing. Overall, it is likely that different medications will be needed to target distinct aspects of problematic cannabis use: craving, ongoing use, withdrawal and relapse. Continued research is needed in preclinical, laboratory and clinical settings. PMID:24955304

  1. The neuropsychiatry of Parkinson's disease.

    Science.gov (United States)

    Lauterbach, E C

    2005-06-01

    The neuropsychiatry of Parkinson's disease (PD) and its correlates are reviewed. Dementia occurs in up to 30% and can be treated with cholinesterase inhibitors. Cognitive impairments involve executive, visuospatial, attentional, and memory dysfunctions. Apathy may respond to dopamine agonists or cholines-terase inhibitors. Cognitive impairment, psychosis, and depression predict quality of life. Visual hallucinations and paranoia are common, and respond to low dose clozapine. Depression is common and predicts caregiver burden and depression. The best data suggest the efficacy of nortriptyline and the safety of SSRIs. Anxiety disorders occur in 40% of patients, especially off-period panic attacks and specific phobias. Bromazepam has proven useful for anxiety in PD, but buspirone has only diminished drug-induced dyskinesias to date. Sleep disorders occur in up to 94% of patients. Insomnia is common and is treated by dopaminergic agent dose reduction, nocturnal dosing, treatment of depression, or use of short half-lived hypnotics, depending on etiology. Parasomnias include REM behavior disorder and vivid dreams and nightmares. Excessive daytime somnolence occurs in at least 15% of patients. Sleep attacks are common and patients should be warned about driving when taking dopamine agonists. Sexual disorders occur in most patients. Paraphilias are associated with dopamine agonists, and clozapine may be useful in their treatment. Surgical therapies are associated with a wide variety of neuropsychiatric features, and vigilance for suicide attempts with subthalamic nucleus stimulation seems warranted. Neuropsychiatric disorders are important determinants of quality of life and caregiver burden in PD. More clinical research is needed to establish effective treatments. PMID:16175159

  2. The Preclinical and Clinical Effects of Vilazodone for the Treatment of Major Depressive Disorder

    Science.gov (United States)

    Sahli, Zeyad T.; Banerjee, Pradeep; Tarazi, Frank I.

    2016-01-01

    ABSTRACT Introduction: Major depressive disorder (MDD) is the leading cause of disability worldwide, and according to the STAR*D trial, only 33% of patients with MDD responded to initial drug therapy. Augmentation of the leading class of antidepressant treatment, selective serotonin reuptake inhibitors (SSRIs), with the 5-HT1A receptor agonist buspirone has been shown to be effective in treating patients that do not respond to initial SSRI therapy. This suggests that newer treatments may improve the clinical picture of MDD. The US Food and Drug Administration (FDA) approved the antidepressant drug vilazodone (EMD 68843), a novel SSRI and 5-HT1A receptor partial agonist. Vilazodone has a half-life between 20–24 hours, reaches peak plasma concentrations at 3.7–5.3 hours, and is primarily metabolized by the hepatic CYP450 3A4 enzyme system. Areas covered: The authors review the preclinical and clinical profile of vilazodone. The roles of serotonin, the 5-HT1A receptor, and current pharmacotherapy approaches for MDD are briefly reviewed. Next, the preclinical pharmacological, behavioral, and physiological effects of vilazodone are presented, followed by the pharmacokinetic properties and metabolism of vilazodone in humans. Last, a brief summary of the main efficacy, safety, and tolerability outcomes of clinical trials of vilazodone is provided. Expert opinion: Vilazodone has shown efficacy versus placebo in improving depression symptoms in several double-blind, placebo-controlled trials. The long-term safety and tolerability of vilazodone treatment has also been established. Further studies are needed that directly compare patients treated with an SSRI (both with and without an adjunctive 5-HT1A partial agonist) versus patients treated with vilaozodone. PMID:26971593

  3. Effects of high-dilutions in behavioural models: a commentary on critical issues, from reproducibility to plausibility

    Directory of Open Access Journals (Sweden)

    Elisabetta Zanolin

    2011-12-01

    Full Text Available As part of a rigorous investigation into the effects of Gelsemium sempervirens on laboratory mice, we performed two complete series of experiments and published three scientific papers. A recent commentary has, however, called into question the reproducibility and validity of these findings. In this article we discuss the major issues raised by this critique within the framework of methodological aspects and the interpretation of results of high-dilution and homeopathic research. The charge of non-reproducibility is shown to be unfounded, because a same homeopathic medicine displayed the same direction of effects in two well-validated models (light-dark and open-field, albeit with nonlinear patterns. The double-blind protocols and statistics by means of ANOVA were performed appropriately and the difference between dilutions of Gelsemium (5cH, 7cH, 9cH and 30cH with variations according to model and placebo was statistically highly significant. Our investigations brought to light some problems related with the lack of activity of buspirone and diazepam (conventional anxiolytic drugs used as control on some behavioural parameters, suggesting that Gelsemium may have broader action, and raising doubts as to the reliability of benzodiazepines as positive controls for homeopathic treatments. Concerning the plausibility of experiments in this field, disputed on the grounds of alleged lack of dose-response effect, we note that the latter is not at all uncommon, and can be accounted for by a host of possible reasons. In conclusion, our research line showed reproducible and consistent effects of Gelsemium in laboratory mice.

  4. Synergistic drug-cytokine induction of hepatocellular death as an in vitro approach for the study of inflammation-associated idiosyncratic drug hepatotoxicity

    International Nuclear Information System (INIS)

    Idiosyncratic drug hepatotoxicity represents a major problem in drug development due to inadequacy of current preclinical screening assays, but recently established rodent models utilizing bacterial LPS co-administration to induce an inflammatory background have successfully reproduced idiosyncratic hepatotoxicity signatures for certain drugs. However, the low-throughput nature of these models renders them problematic for employment as preclinical screening assays. Here, we present an analogous, but high-throughput, in vitro approach in which drugs are administered to a variety of cell types (primary human and rat hepatocytes and the human HepG2 cell line) across a landscape of inflammatory contexts containing LPS and cytokines TNF, IFNγ, IL-1α, and IL-6. Using this assay, we observed drug-cytokine hepatotoxicity synergies for multiple idiosyncratic hepatotoxicants (ranitidine, trovafloxacin, nefazodone, nimesulide, clarithromycin, and telithromycin) but not for their corresponding non-toxic control compounds (famotidine, levofloxacin, buspirone, and aspirin). A larger compendium of drug-cytokine mix hepatotoxicity data demonstrated that hepatotoxicity synergies were largely potentiated by TNF, IL-1α, and LPS within the context of multi-cytokine mixes. Then, we screened 90 drugs for cytokine synergy in human hepatocytes and found that a significantly larger fraction of the idiosyncratic hepatotoxicants (19%) synergized with a single cytokine mix than did the non-hepatotoxic drugs (3%). Finally, we used an information theoretic approach to ascertain especially informative subsets of cytokine treatments for most highly effective construction of regression models for drug- and cytokine mix-induced hepatotoxicities across these cell systems. Our results suggest that this drug-cytokine co-treatment approach could provide a useful preclinical tool for investigating inflammation-associated idiosyncratic drug hepatotoxicity.

  5. An Automated High-Throughput Metabolic Stability Assay Using an Integrated High-Resolution Accurate Mass Method and Automated Data Analysis Software

    Science.gov (United States)

    Shah, Pranav; Kerns, Edward; Nguyen, Dac-Trung; Obach, R. Scott; Wang, Amy Q.; Zakharov, Alexey; McKew, John; Simeonov, Anton; Hop, Cornelis E. C. A.

    2016-01-01

    Advancement of in silico tools would be enabled by the availability of data for metabolic reaction rates and intrinsic clearance (CLint) of a diverse compound structure data set by specific metabolic enzymes. Our goal is to measure CLint for a large set of compounds with each major human cytochrome P450 (P450) isozyme. To achieve our goal, it is of utmost importance to develop an automated, robust, sensitive, high-throughput metabolic stability assay that can efficiently handle a large volume of compound sets. The substrate depletion method [in vitro half-life (t1/2) method] was chosen to determine CLint. The assay (384-well format) consisted of three parts: 1) a robotic system for incubation and sample cleanup; 2) two different integrated, ultraperformance liquid chromatography/mass spectrometry (UPLC/MS) platforms to determine the percent remaining of parent compound, and 3) an automated data analysis system. The CYP3A4 assay was evaluated using two long t1/2 compounds, carbamazepine and antipyrine (t1/2 > 30 minutes); one moderate t1/2 compound, ketoconazole (10 < t1/2 < 30 minutes); and two short t1/2 compounds, loperamide and buspirone (t½ < 10 minutes). Interday and intraday precision and accuracy of the assay were within acceptable range (∼12%) for the linear range observed. Using this assay, CYP3A4 CLint and t1/2 values for more than 3000 compounds were measured. This high-throughput, automated, and robust assay allows for rapid metabolic stability screening of large compound sets and enables advanced computational modeling for individual human P450 isozymes. PMID:27417180

  6. Application of a cocktail approach to screen cytochrome P450 BM3 libraries for metabolic activity and diversity.

    Science.gov (United States)

    Reinen, Jelle; Postma, Geert; Tump, Cornelis; Bloemberg, Tom; Engel, Jasper; Vermeulen, Nico P E; Commandeur, Jan N M; Honing, Maarten

    2016-02-01

    In the present study, the validity of using a cocktail screening method in combination with a chemometrical data mining approach to evaluate metabolic activity and diversity of drug-metabolizing bacterial Cytochrome P450 (CYP) BM3 mutants was investigated. In addition, the concept of utilizing an in-house-developed library of CYP BM3 mutants as a unique biocatalytic synthetic tool to support medicinal chemistry was evaluated. Metabolic efficiency of the mutant library towards a selection of CYP model substrates, being amitriptyline (AMI), buspirone (BUS), coumarine (COU), dextromethorphan (DEX), diclofenac (DIC) and norethisterone (NET), was investigated. First, metabolic activity of a selection of CYP BM3 mutants was screened against AMI and BUS. Subsequently, for a single CYP BM3 mutant, the effect of co-administration of multiple drugs on the metabolic activity and diversity towards AMI and BUS was investigated. Finally, a cocktail of AMI, BUS, COU, DEX, DIC and NET was screened against the whole in-house CYP BM3 library. Different validated quantitative and qualitative (U)HPLC-MS/MS-based analytical methods were applied to screen for substrate depletion and targeted product formation, followed by a more in-depth screen for metabolic diversity. A chemometrical approach was used to mine all data to search for unique metabolic properties of the mutants and allow classification of the mutants. The latter would open the possibility of obtaining a more in-depth mechanistic understanding of the metabolites. The presented method is the first MS-based method to screen CYP BM3 mutant libraries for diversity in combination with a chemometrical approach to interpret results and visualize differences between the tested mutants.

  7. Zebrafish assessment of cognitive improvement and anxiolysis: filling the gap between in vitro and rodent models for drug development.

    Science.gov (United States)

    Levin, Edward D

    2011-01-01

    Zebrafish can provide a valuable animal model to screen potential cognitive enhancing and anxiolytic drugs. They are economical and can provide a relatively quick indication of possible functional efficacy. In as much as they have a complex nervous system and elaborate behavioral repertoire, zebrafish can provide a good intermediate model between in vitro receptor and cell-based assays and classic mammalian models for drug screening. In addition, the variety of molecular tools available in zebrafish makes them outstanding models for helping to determine the neuromolecular mechanisms for psychoactive drugs. However, to use zebrafish as a translational model we must have validated, sensitive and efficient behavioral tests. In a series of studies, our lab has developed tests of cognitive function and stress response, which are sensitive to drug effects in a similar manner as rodent models and humans for cognitive enhancement and alleviating stress response. In particular, the three-chamber task for learning and memory was shown to be sensitive to the cognitive enhancing effects of nicotine and has been useful in helping to determine neural mechanisms crucial for nicotinic-induced cognitive enhancement. The novel tank diving test was shown to be a valid and efficient test of stress response. It is sensitive to the reduction in stress-related behaviors due to the amxiolytic drugs diazepam and buspirone but not chlordiazepoxide. Nicotine also causes stress alleviating effects which can be interpreted as anxiolytic effects. Zebrafish models of behavioral pharmacology can be useful to efficiently screen test compounds for drug development and can be useful in helping to determine the mechanisms crucial for new therapeutic treatments of neurobehavioral impairments.

  8. Dopamine D3 receptor ligands for drug addiction treatment: update on recent findings.

    Science.gov (United States)

    Le Foll, Bernard; Collo, Ginetta; Rabiner, Eugenii A; Boileau, Isabelle; Merlo Pich, Emilio; Sokoloff, Pierre

    2014-01-01

    The dopamine D3 receptor is located in the limbic area and apparently mediates selective effects on motivation to take drugs and drug-seeking behaviors, so that there has been considerable interest on the possible use of D3 receptor ligands to treat drug addiction. However, only recently selective tools allowing studying this receptor have been developed. This chapter presents an overview of findings that were presented at a symposium on the conference Dopamine 2013 in Sardinia in May 2013. Novel neurobiological findings indicate that drugs of abuse can lead to significant structural plasticity in rodent brain and that this is dependent on the availability of functional dopamine D3 autoreceptor, whose activation increased phosphorylation in the ERK pathway and in the Akt/mTORC1 pathway indicating the parallel engagement of a series of intracellular signaling pathways all involved in cell growth and survival. Preclinical findings using animal models of drug-seeking behaviors confirm that D3 antagonists have a promising profile to treat drug addiction across drugs of abuse type. Imaging the D3 is now feasible in human subjects. Notably, the development of (+)-4-propyl-9-hydroxynaphthoxazine ligand used in positron emission tomography (PET) studies in humans allows to measure D3 and D2 receptors based on the area of the brain under study. This PET ligand has been used to confirm up-regulation of D3 sites in psychostimulant users and to reveal that tobacco smoking produces elevation of dopamine at the level of D3 sites. There are now novel antagonists being developed, but also old drugs such as buspirone, that are available to test the D3 hypothesis in humans. The first results of clinical investigations are now being provided. Overall, those recent findings support further exploration of D3 ligands to treat drug addiction. PMID:24968784

  9. Towards safer and more predictable drug treatment--reflections from studies of the First BCPT Prize awardee.

    Science.gov (United States)

    Neuvonen, Pertti J

    2012-03-01

    This MiniReview is a personal recollection of selected research topics, which the author in collaboration with colleagues has studied, aiming to improve the predictability of drug therapy. In early studies, we found bi- and trivalent cations to reduce the absorption of various tetracyclines and fluoroquinolones. Certain antacids elevated the bioavailability of some non-steroidal anti-inflammatory drugs and sulphonylureas. Various brands of phenytoin tablets revealed great differences in their bioavailability, causing clinical consequences. Numerous factors affecting the antidotal effect of activated charcoal were also studied, with charcoal compared to other gastrointestinal decontamination methods, including ipecac and gastric lavage. Effect of age and diseases on the pharmacokinetics of drugs was a research topic. Acute sotalol intoxications revealed its QT-prolonging properties, and even small mixed overdoses of moclobemide with serotonergic drugs proved fatal. Itraconazole and other potent inhibitors of CYP3A4 could drastically increase exposure to drugs like midazolam, triazolam, buspirone, lovastatin, simvastatin and oxycodone, whereas rifampicin greatly reduced their plasma concentrations. A change from potent inhibition to induction caused a 400-fold change in the exposure to oral midazolam. CYP2C8 was revealed to be crucial in the metabolism and interactions of several drugs. Many interactions affecting statins are CYP3A4-mediated, but transporters are important in certain interactions. Tizanidine is very susceptible to CYP1A2 inhibition. Fruit juices such as grapefruit juice can raise or lower exposure to different drugs. Both drug interactions and pharmacogenetics can modify the activity of cell membrane transporters and cause variability in the pharmacokinetics of and response to their substrate drugs.

  10. Treatment of the irritable bowel syndrome.

    Science.gov (United States)

    Friedman, G

    1991-06-01

    Individualization of treatment for patients with IBS is predicated on a thorough analysis of the patient's symptoms, consideration of the reasons for seeking health care, evaluation of symptom-precipitating factors, elimination of confounding features, and the absolute knowledge of the absence of organic illness. Collecting and codifying appropriate historical data allow the physician to educate the patient with respect to the origin of his symptoms, and to enlist the patient as a partner in his future health care. There is no single, universally accepted therapeutic agent available for the treatment of the IBS patient. As a result, treatment is directed at reducing the frequency and intensity of triggering factors as well as ameliorating the symptoms when they arise. Symptoms evoked by psychologic factors may be effectively reduced by psychotherapy or hypnotherapy. Situational anxiety may be treated for brief periods by using antianxiety agents such as diazepam, chlordiazepoxide, buspirone, or similar agents. Depressive reactions may be reduced with suitable doses of antidepressant agents such as amitriptyline. Smooth muscle hyperreactivity may be dulled with small amounts of selected anticholinergics, which are usually most effective in reducing meal-induced discomfort. Peppermint oil may be of additional benefit. Gas-related symptoms require elimination of contributory dietary factors, such as lactose-containing foods, sorbitol, or fructose, as well as certain oligosaccharides. Simethecone, charcoal, or beanase may be helpful. Functional constipation is best treated with graded doses of insoluble or soluble fiber. Diarrheal episodes may be reduced with either loperamide or diphenoxylate. Careful, continued follow-up assessment of therapeutic endeavors, a sincere interest in the patient's concerns, and surveillance for intercurrent organic illness are the cornerstones of complete ongoing care. PMID:2066156

  11. Glutarimides: Biological activity, general synthetic methods and physicochemical properties

    Directory of Open Access Journals (Sweden)

    Popović-Đorđević Jelena B.

    2015-01-01

    Full Text Available Glutarimides, 2,6-dioxopiperidines are compounds that rarely occur in natural sources, but so far isolated ones exert widespread pharmacological activities, which makes them valuable as potential pharmacotherapeutics. Glutarimides act as androgen receptor antagonists, anti-inflammatory, anxiolytics, antibacterials, and tumor suppressing agents. Some synthetic glutarimide derivatives are already in use as immunosuppressive and sedative (e.g., thalidomide or anxiolytics (buspirone drugs. The wide applicability of this class of compounds, justify the interest of scientists to explore new pathways for its syntheses. General methods for synthesis of six-membered imide ring, are presented in this paper. These methods include: a reaction of dicarboxylic acids with ammonia or primary amine, b reactions of cyclization: amido-acids, diamides, dinitriles, nitrilo-acids, amido-nitriles, amido-esters, amidoacyl-chlorides or diacyl-chlorides, c adition of carbon-monoxide on a,b-unsaturated amides, d oxidation reactions, e Michael adition of active methylen compounds on methacrylamide or conjugated amides. Some of the described methods are used for closing glutarimide ring in syntheses of farmacological active compounds sesbanimide and aldose reductase inhibitors (ARI. Analyses of the geometry, as well as, the spectroscopic analyses (NMR and FT-IR of some glutarimides are presented because of their broad spectrum of pharmacological activity. To elucidate structures of glutarimides, geometrical parameters of newly synthesized tert-pentyl-1-benzyl-4-methyl-glutarimide-3-carboxylate (PBMG are analyzed and compared with the experimental data from X-ray analysis for glutarimide. Moreover, molecular electrostatic potential (MEP surface which is plotted over the optimized geometry to elucidate the reactivity of PBMG molecule is analyzed. The electronic properties of glutarimide derivatives are explained on the example of thalidomide. The Frontier Molecular Orbital

  12. iPhone® applications as versatile video tracking tools to analyze behavior in zebrafish (Danio rerio).

    Science.gov (United States)

    Pittman, Julian T; Ichikawa, Katie M

    2013-05-01

    Zebrafish (Danio rerio) are emerging as a promising model organism for experimental studies relevant to biological psychiatry. The objective of this study was to develop a novel video-based movement tracking and analysis system to quantify behavioral changes following psychoactive drug exposure in zebrafish. We assessed the effects of withdrawal from chronic ethanol exposure, and subsequent administration of fluoxetine (Prozac®), buspirone (Buspar®), and diazepam (Valium) using two behavioral paradigms; the Novel Tank Diving Test and the Light/Dark Choice Assay. A video tracking system was developed using two Apple® applications (Apps) to quantify these behaviors. Data from zebrafish exposed to the above treatments are presented in this paper not only to exemplify behavioral alterations associated with chronic exposure, but also more importantly, to validate the video tracking system. Following withdrawal from chronic ethanol exposure, zebrafish exhibited dose/time-dependent anxiogenic effects; including reduced exploration and freezing behavior in the Novel Tank Diving Test, and preference for the dark area for the Light/Dark Choice Assay. In contrast, the above drug treatments had significant anxiolytic effects. We have developed a simple and cost-effective method of measuring zebrafish behavioral responses. The iPhone® Apps outlined in this study offer numerous flexible methods of data acquisition; namely, ease of identification and tracking of multiple animals, tools for visualization of the tracks, and calculation of a range of analysis parameters. Furthermore, the limited amount of time required for interpretation of the video data makes this a powerful high-throughput tool with potential applications for pre-clinical drug development.

  13. A comparsion study on the social functions promotion of different medicine treatment strategies on the patients with treatment-resistant depression%不同药物治疗方案对难治性抑郁症患者社会功能的影响

    Institute of Scientific and Technical Information of China (English)

    卢卫红; 方贻儒; 苑成梅; 易正辉; 汪作为; 陈俊; 吴志国; 洪武; 胡莺燕; 曹岚

    2010-01-01

    Objective To evaluate the effectiveness of different medicine treatment strategies on the social functions promotion on the patients with treatment-resistant depression (TRD). Methods 375 Patients with TRD were randomly grouped into 8 groups, and each group was received 8 weeks different treatment for paroxetine,venlafaxine, mirtazapine, paroxetine plus risperidone, paroxetine plus sodium valproate, paroxetine plus buspirone, paroxetine plus trazodone,or paroxetine plus thyroxine, respectively. The efficacy and social functions were evaluated with HAMD-17, SDSS and SF-36. Results There were significant difference in SDSS scores between 8th week and the baseline( P<0.01 ) , and for social functions factor scores of SF-36 there was significant difference between 4th ,8th week and the baseline in each groups( P<0.01 ). There were significant difference in social functions factor scores of SF-36 and subtracting scores between 4th and 8th week in all groups except group paroxetine and group venlafaxine(P < 0.05 or P < 0.01 ). There were significant difference in SDSS subtracting scores at 8th week among 8 groups( paroxetine plus risperidone group 7.05 ± 6.39, mirtazapine group 6.53 ± 4.75, paroxetine plusthyroxine group 5.14 ± 4.94, paroxetine group 5.13 ± 4.94 ,paroxetine plus trazodone group 5.00 ± 4.94, paroxetine plus sodium valproate group 4.60 ± 4.09, venlafaxine group 4.57 ± 4.18, paroxetine plus buspirone group 4.24 ± 4.95 ) ( Z = 2.076, P < 0.05 ), between group paroxetine plus risperidone and group venlafaxine , group paroxetine plus sodium valproate, group paroxetine plus buspirone,as group mirtazapine and group paroxetine plus buspirone(P< 0.05 ), respectively. The influencing factors on improving social functions are the severity, improvement of depressive symptoms and latest onset time. Conclusions These 8 treatment strategies all can promote social functions on the patients with TRD. But the intensity and chronological order of

  14. Vilazodone does not inhibit sexual behavior in male rats in contrast to paroxetine: A role for 5-HT1A receptors?

    Science.gov (United States)

    Oosting, Ronald S; Chan, Johnny S W; Olivier, Berend; Banerjee, Pradeep

    2016-08-01

    Vilazodone (VLZ) is a selective serotonin reuptake inhibitor (SSRI) and 5-HT1A receptor partial agonist approved for the treatment of major depressive disorder in adults. In preclinical studies, VLZ had significantly lower sexual side effects than SSRIs and reduced serotonin transporter (SERT) levels in forebrain regions. In the current study, once-daily paroxetine (PAR, 10 mg/kg), VLZ (10 mg/kg), PAR + buspirone (BUS, 3 mg/kg; a 5-HT1A partial agonist), or vehicle (VEH) was administered to male rats for 2 weeks then switched for 7 days (eg, PAR switched to VLZ, PAR + BUS, or VEH). Sexual behavior (eg, ejaculation frequency and latency) was evaluated 1-hr postdose on days 1, 7, 14, and 21. After 2 weeks, treatment with PAR but not VLZ resulted in a significant decrease in sexual behavior. In a 30-min test, the range of ejaculation frequency was 3.08-3.5 with VLZ and 1.00-1.92 with PAR (P < 0.05 vs VEH). After switching from PAR to VEH, PAR + BUS, or VEH, sexual behaviors were normalized to control levels. In contrast, the switch from VLZ to PAR resulted in reduced sexual behaviors. This preclinical study showed that unlike PAR, an SSRI with no 5-HT1A receptor activity, initial treatment with VLZ did not result in sexual side effects at therapeutically relevant doses. Results in male rats switched from PAR to VLZ or PAR + BUS strongly suggest that activation of 5-HT1A receptors may mitigate the sexual side effects associated with conventional SSRIs. PMID:27040795

  15. Quantitative methods in electroencephalography to access therapeutic response.

    Science.gov (United States)

    Diniz, Roseane Costa; Fontenele, Andrea Martins Melo; Carmo, Luiza Helena Araújo do; Ribeiro, Aurea Celeste da Costa; Sales, Fábio Henrique Silva; Monteiro, Sally Cristina Moutinho; Sousa, Ana Karoline Ferreira de Castro

    2016-07-01

    Pharmacometrics or Quantitative Pharmacology aims to quantitatively analyze the interaction between drugs and patients whose tripod: pharmacokinetics, pharmacodynamics and disease monitoring to identify variability in drug response. Being the subject of central interest in the training of pharmacists, this work was out with a view to promoting this idea on methods to access the therapeutic response of drugs with central action. This paper discusses quantitative methods (Fast Fourier Transform, Magnitude Square Coherence, Conditional Entropy, Generalised Linear semi-canonical Correlation Analysis, Statistical Parametric Network and Mutual Information Function) used to evaluate the EEG signals obtained after administration regimen of drugs, the main findings and their clinical relevance, pointing it as a contribution to construction of different pharmaceutical practice. Peter Anderer et. al in 2000 showed the effect of 20mg of buspirone in 20 healthy subjects after 1, 2, 4, 6 and 8h after oral ingestion of the drug. The areas of increased power of the theta frequency occurred mainly in the temporo-occipital - parietal region. It has been shown by Sampaio et al., 2007 that the use of bromazepam, which allows the release of GABA (gamma amino butyric acid), an inhibitory neurotransmitter of the central nervous system could theoretically promote dissociation of cortical functional areas, a decrease of functional connectivity, a decrease of cognitive functions by means of smaller coherence (electrophysiological magnitude measured from the EEG by software) values. Ahmad Khodayari-Rostamabad et al. in 2015 talk that such a measure could be a useful clinical tool potentially to assess adverse effects of opioids and hence give rise to treatment guidelines. There was the relation between changes in pain intensity and brain sources (at maximum activity locations) during remifentanil infusion despite its potent analgesic effect. The statement of mathematical and computational

  16. Modulation of the vagal bradycardia evoked by stimulation of upper airway receptors by central 5-HT1 receptors in anaesthetized rabbits

    Science.gov (United States)

    Dando, Simon B; Skinner, Matthew R; Jordan, David; Ramage, Andrew G

    1998-01-01

    The effects of central application of 5-HT1A and 5-HT1B/1D receptor ligands on the reflex bradycardia, apnoea, renal sympathoexcitation and pressor response evoked by stimulating upper airway receptors with smoke in atenolol-pretreated anaesthetized rabbits were studied.Intracisternal administration of the 5-HT1A receptor antagonists WAY-100635 (100 μg kg−1) and (−)pindolol (100 μg kg−1) significantly reduced the smoke-induced bradycardia, attenuated the pressor response and in the case of (−)pindolol, sympathetic nerve activity. The same dose of WAY-100635 i.v. was without effect.Buspirone (200 μg kg−1, i.c.) potentiated the reflex bradycardia. This action was prevented if the animals were pretreated with WAY-100635 (100 μg kg−1, i.v.)(+)8-OH-DPAT (25 μg kg−1, i.c.) attenuated the evoked bradycardia, pressor response, apnoea and renal sympathoexcitation. The attenuation of the apnoea and renal sympathoexcitation, but not the bradycardia or pressor response was prevented in animals pretreated with WAY-100635 (100 μg kg−1, i.v.). The attenuation of the reflex bradycardia and the reduction in the renal sympathoexcitation were reduced by pretreatment with the 5-HT1B/1D receptor antagonist GR127935 (100 μg kg−1, i.v.).In WAY-100635 (100 μg kg−1, i.v.) pretreated animals, sumatriptan (a 5-HT1B/1D receptor agonist) reduced the reflex bradycardia and the pressor response. The 5-HT1B/1D receptor antagonist GR127935 (20 μg kg−1, i.c. or 100 μg kg−1, i.v.) had no effect on the reflex responses.In conclusion, the present data are consistent with the hypothesis that activation of central 5-HT1A receptors potentiate whilst activation of 5-HT1B/1D receptors attenuate the reflex activation of cardiac preganglionic vagal motoneurones evoked by stimulation of upper airway receptors with smoke in rabbits. PMID:9786516

  17. Anxiety in Patients with Schizophrenia: Epidemiology and Management.

    Science.gov (United States)

    Temmingh, Henk; Stein, Dan J

    2015-10-01

    randomized and open trials have shown that aripiprazole and risperidone may be efficacious for obsessive-compulsive and social anxiety symptoms, and quetiapine and olanzapine for generalized anxiety. Older agents such as trifluoperazine may also reduce comorbid anxiety symptoms. Alternative options include selective serotonin re-uptake inhibitor (SSRI) augmentation of antipsychotics, although evidence is based on a few randomized trials, small open trials, and case series, and caution is needed with regards to cytochrome P450 interactions and QTc interval prolongation. Buspirone and pregabalin augmentation may also be considered. Diagnosis and treatment of anxiety symptoms and disorders in schizophrenia is an important and often neglected aspect of the management of schizophrenia. PMID:26482261

  18. Use of PET and the radioligand [carbonyl-{sup 11}C]WAY-100635 in psychotropic drug development

    Energy Technology Data Exchange (ETDEWEB)

    Andree, Bengt; Halldin, Christer; Thorberg, Seth-Olov; Sandell, Johan; Farde, Lars

    2000-07-01

    Positron-emission tomography (PET) provides potential in neuropsychiatric drug development by expanding knowledge of drug action in the living human brain and reducing time consumption and costs. The 5-hydroxytryptamine{sub 1A} (5-HT{sub 1A}) receptor is of central interest as a target for the treatment of anxiety, depression, and schizophrenia. Research on the clinical significance of the 5-HT{sub 1A} receptor now benefits from the highly selective radioligand [carbonyl-{sup 11}C]WAY-100635 (WAY) for quantitative determination of 5-HT{sub 1A} receptors in the primate and human brain in vivo using PET. In this paper, three studies are reviewed to demonstrate the suitability of WAY as radioligand for quantification of central 5-HT{sub 1A} receptors in brain and as an applicable tool for drug development. In the first study a monkey model was used to characterize WAY binding. It was confirmed that the reference ligand 8-OH-DPAT and psychoactive drugs such as buspirone and pindolol occupies 5-HT{sub 1A} receptors in the primate brain. Pindolol is an {beta}-adrenoreceptor antagonist with a high affinity to 5-HT{sub 1A} receptors. This drug has been suggested in combination with selective serotonin reuptake inhibitors for the treatment of depression and was given to healthy males in the second study. Pindolol induced a marked inhibition of central 5-HT{sub 1A} receptors as calculated by the ratio-analysis method and simplified reference tissue model, 2 h after administration of 10 mg as a single oral dose. This observation suggests that pindolol may have a role for the suggested potentiation of selective serotonin reuptake inhibitor treatment of depression. The third study was on robalzotan (NAD-299), a recently developed 5-HT{sub 1A} receptor antagonist and putative drug with implications for the treatment of depression. In the cynomolgus monkey brain, robalzotan in the dose range 2-100 {mu}g/kg IV occupied 5-HT{sub 1A} receptors in a dose-dependent and saturable

  19. Anxiolytic-like actions of BW 723C86 in the rat Vogel conflict test are 5-HT2B receptor mediated.

    Science.gov (United States)

    Kennett, G A; Trail, B; Bright, F

    1998-12-01

    The 5-HT2B receptor agonist, BW 723C86 (10, 30(mg/kg i.p. 30 min pre-test), increased the number of punishments accepted in a rat Vogel drinking conflict paradigm over 3 min, as did the benzodiazepine anxiolytics, chlordiazepoxide (2.5-10 mg/kg p.o. 1 h pre-test) and alprazolam (0.2-5 mg/kg p.o. 1 h pre-test), but not the 5-HT2C/2B receptor agonist, m-chlorophenylpiperazine (mCPP, 0.3-3 mg/kg i.p) or the 5-HT1A receptor agonist, buspirone (5-20 mg/kg p.o. 1 h pre-test). The effect of BW 723C86 was unlikely to be secondary to enhanced thirst, as BW 723C86 did not increase the time that rats with free access to water spent drinking, nor did it reduce sensitivity to shock in the apparatus. The anti-punishment effect of BW 723C86 was opposed by prior treatment with the 5-HT2/2B receptor antagonist, SB-206553 (10 and 20 mg/kg p.o. 1 h pre-test), and the selective 5-HT2B receptor antagonist, SB-215505 (1 and 3 mg/kg p.o. 1 h pre-test), but not by the selective 5-HT2C receptor antagonist, SB-242084 (5 mg/kg p.o.), or the 5-HT1A receptor antagonist, WAY 100635 (0.1 or 0.3 mg/kg s.c. 30 min pre-test). Thus, the anti-punishment action of BW 723C86 is likely to be 5-HT2B receptor mediated. This is consistent with previous reports that BW 723C86 exhibited anxiolytic-like properties in both the social interaction and Geller-Seifter conflict tests. PMID:9886683

  20. Anxiolytic-like effects of carvacryl acetate, a derivative of carvacrol, in mice.

    Science.gov (United States)

    Pires, Lúcio Fernandes; Costa, Luciana Muratori; Silva, Oskar Almeida; de Almeida, Antonia Amanda Cardoso; Cerqueira, Gilberto Santos; de Sousa, Damião Pergentino; de Freitas, Rivelilson Mendes

    2013-11-01

    Studies showing anxiolytic-like properties of natural products have grown. This paper evaluated if carvacryl acetate (CA) could be studied as an alternative drug to treat anxiety disorders. Elevated plus maze (EPM) tests , light-dark box (LDB) tests, and marble-burying tests (MBTs) were performed on mice. In the first protocol, the anxiolytic-like activities of CA 25, 50, 75 and 100mg/kg at single doses were compared to those of the vehicle, buspirone 5mg/kg (BUSP) and diazepam 1mg/kg (DZP). In the second protocol, the anxiolytic-like actions of CA were tested for GABAergic and serotonergic systems. The time spent in the open arms (TSOA) and the number of open arms entries (NOAE) were measured in EPM; the time spent in the light box (TSLB) and the number of entries to light box (NELB) were measured in LDB; and the number of marbles buried (NMB) were measured in MBT. CA increased TSOA and NOAE in the EPM, as well as TSLB and NELB in the LDB and the NMB in the MBT. The anxiolytic-like activity of CA 25; 50; 75 and 100mg/kg was not associated with psychomotor retardation in the open field test and in the Rota rod test, contrarily with what happened with DZP. In the second protocol, to suggest the mechanism of action of CA, flumazenil 25mg/kg ip (FLU) and WAY 100,635 10mg/kg ip (WAY-5-HT1A antagonist) were also used. FLU+CA100 reduced TSOA in the EPM when compared to CA100 but WAY+CA100 did not. In LDB, FLU+CA100 reduced the TSLB when compared to CA100 but WAY+CA100 did not. In the MBT, FLU+CA100 inhibited the effect of CA100 on the NMB but WAY+CA100 did not. In conclusion, CA seems to have an anxiolytic-like effect, probably due to GABAergic agonist action, without psychomotor side effects.

  1. Use of anti-anxiety drugs in the medically ill.

    Science.gov (United States)

    Wheatley, D

    1988-01-01

    The Stress Clinic at the Maudsley Hospital investigates anxiety due to stress and its pharmacological treatment. Nine stress areas are investigated and their relative severities estimated: social habits, social relationships, life events, psychiatric morbidity, sexual stresses, sleep, stress in old age, menstrual stresses and stress and the heart. From the results a Stress Profile can be constructed for each patient to compare the importance of these different stresses and this can also be used as a measure of change in response to treatment. The benzodiazepine (BZD) anxiolytics can be divided into two groups according to duration of action, medium (8-12 h) and long (30-100 h). Short-acting BZD drugs are particularly useful for situational anxiety, when treatment can be interrupted over night and at weekends. To overcome problems of dependence, withdrawal effects, and daytime side-effects, new non-BZD anxiolytics have been developed: buspirone, alpidem and suriclone. These may be particularly useful for long-term treatment of anxiety. Another alternative is the use of adrenergic beta-blocking drugs of which propranolol and betaxolol have been used in the Clinic, because of their relatively high concentration in the brain when taken orally. Anxiety accompanying coronary heart disease and hypertension can be controlled with anxiolytic drugs and other illnesses with an anxiety component are: sexual disorders, menstrual disorders, asthma, gastro-intestinal conditions, dermatological conditions and chronic illnesses such as malignancy and AIDS. Lack of sleep is a subtle form of stress exerting an adverse effect in almost every illness known to man. BZD hypnotics can be divided into four groups: ultra-short-acting (3-4 h), short-acting (5-6 h), medium-acting (7-8 h) and long-acting (9-12 h). Depending on the nature of the insomnia, ultra-short-acting and short-acting BZD are particularly convenient with minimal disadvantages. Nevertheless, new non-BZD hypnotics are also

  2. Plantas medicinais no tratamento do transtorno de ansiedade generalizada: uma revisão dos estudos clínicos controlados Medicinal plants for the treatment of generalized anxiety disorder: a review of controlled clinical studies

    Directory of Open Access Journals (Sweden)

    Thalita Thais Faustino

    2010-12-01

    medicinal (OR specific name plants" e "anxie* OR anxioly* OR tranquil* OR GAD", limited to "human OR clinical trial OR randomized controlled trial OR meta-analysis OR review". The search was restricted to English language. RESULTS: Piper methysticum presented an unequivocal anxiolytic effect, but most studies also included patients with other anxiety disorders (e.g. phobias. Isolated studies with Ginkgo biloba, Galphimia glauca, Matricaria recutita, Passiflora incarnata and Valeriana officinalis showed a potential use for anxious diseases. Despite this low number of studies, Ginkgo biloba and Matricaria recutita showed an effect size (Cohen's d = 0.47 to 0.87 similar or higher to standard anxiolytics drugs (benzodiazepines, buspirone and antidepressants - 0.17 to 0.38. No additional study with other plants was found. CONCLUSION: Despite the therapeutic potential of medicinal plants in generalized anxiety disorder, very few controlled trials assessing herbal medicines in generalized anxiety disorder were found. Additionally, these studies present serious flaw design.

  3. Retrospective comparison of cognitive behavioral therapy and symptom-specific medication to treat anxiety and depression in throat cancer patients after laryngectomy%认知行为治疗和症状特异性药物治疗伴焦虑和抑郁的喉切除术后咽喉癌患者的回顾性比较

    Institute of Scientific and Technical Information of China (English)

    陈静; 陈传成; 支胜利

    2014-01-01

      讨论:CBT是一种有效的、短期的治疗手段,可用于减少一个人被诊断患有癌症或接受癌症治疗后往往产生的焦虑和抑郁症状。众多证据表明,这些心理症状的治疗可以提高癌症患者的生活质量和减短疾病的病程,所以肿瘤学家和其他临床医生需要定期筛查癌症患者和其他危及生命的慢性病患者的抑郁和焦虑症状,如果存在的话,就需要积极对这些症状进行治疗。这项研究表明,CBT对于即使无法说话的癌症患者来说也是有效的。%Background:Laryngectomy, a common treatment for laryngeal cancer, is a disabling operation that can induce tremendous stress, but little is known about how to alleviate the psychological effects of the operaiton. Aim:Compare the effecitveness of cogniitve behavioral therapy (CBT) and medicaiton in treaitng anxiety and depression among throat cancer paitents atfer laryngectomy. Methods:Review of medical records of the psychological outpaitent clinic in the Third People’s Hospital of Huzhou City between March 2009 and May 2013 idenitifed 63 paitents with post-laryngectomy depression or anxiety disorders who received 8 weeks of one-on-one treatment with CBT (in which paitents responded in writing because they were unable to speak) and 56 patients who received 8 weeks of treatment with buspirone (n=11), sertraline (n=9) or both busipirone and sertraline (n=36). The treatment provided (CBT or medicaitons) was based on the stated preference of the paitent. The Zung Self-raitng Anxiety Scale (SAS) and the Zung Self-raitng Depression Scale (SDS) were administered before and atfer treatment. Results:Atfer 8 weeks of treatment the mean SAS and SDS scores had decreased signiifcantly in both groups and the prevalence of clinically signiifcant anxiety and depression (based on SAS and SDS cutoff scores) had dropped dramaitcally. There were, however, no signiifcant differences between the two treatment methods. In

  4. Revista de Revistas.

    Directory of Open Access Journals (Sweden)

    Antonio Nafs

    1991-01-01

    Full Text Available Leyendo Freud en inglés: problemas, paradojas y una solución. Reading Freud in english: problems, paradoxes, and a solution Sander L. Gilman. Ithaca, New York. The International Review of Psycho-Analysis. Vol. 18, Parte-3, Pago 331-344 Antonio Nafs Psiquiatría Infantil: Su relevancia para la Psiquiatría General. K. Minde~ D. Benoit, The Montreal Children's Hospital. Queen's University Kingston, Ontario British Journal of Psychiatry. 1991; 159: 173-184. Daniel Olivares Zarco Síndrome de Stress Post-Traumático en la comunidad: Un estudio epidemiológico. Pos-Traumatic Stress Disorder in the community: An epidemiological study. Jonathan R.T Davidson, Dana Hughes, Dan G. Blazer, Linda K. George. Fronthe. Departament of Psychiatry Duke University Medical Center Durham, North Carolina, USA. Psichological Medicine. Vol 21. N.O 3 Agosto 1991. Pago 713-723 J.C. García Alvarez ¿Puede la buspirona inducir fenómenos de rebote, dependencia o abuso?. Can buspirone induce rebound, dependence or abuse?. Maleolm Lader. British Journal of Psychiatry 1991; 159 (suppl 12: 45-51. M.a Isabel de la Hera Cabero Test de supresión de dexametasona en niños The dexamethasone suppression test in children S.P Tyrer, M.L. Barret, TP Berney, S. Bhate, M.J. Watson, T Fundudis, l. Kolvin British Journal of Psychiatry 1991; 159 (suppl 11: pags 41-48 M.a Isabel de la Hera Cabero Psicodinámica del suicidio, con particular referencia al joven. Psychodynamics of suicide, with particular reference to the young. Herbert Hendin. American Journal of Psychiatry. 148: 9, September 1991. Clara Herráez Martín de Valmaseda Trastornos por uso de sustancias en pacientes con fatiga crónica. Sustance use disorders in patients with chronic fatigue. Henry R. Krazler, Victor M. Hesselbrock, Thomas J. Lane Asociados al Centro Médico de Veteranos de Newington. Prof. Asistente y Prof. del Dpto. de Psiquiatría de la Escuela Universitaria de Medicina de Connecticut. Hospital and

  5. O tratamento farmacológico da fobia social Pharmacologic treatment of social phobia

    Directory of Open Access Journals (Sweden)

    Antonio Egidio Nardi

    1999-12-01

    . There are two specifiers for social phobia: the circumscribed, for those who just fear one situation; and generalized, for those who fear almost all social situations. The clinical features of social phobia are the anticipatory anxiety, the physical symptoms, the avoidance and the low self-esteem. Depending on diagnostic criteria, it is reported a lifetime prevalence ranging from 5% to 13% of the population resulting in different degrees of occupational and social limitations. The ideal treatment should use antidepressant drug and cognitive-behavior therapy. Beta-blocking drugs (atenolol, propranolol, monoamino oxidase inhibitors - MAOI (fenelzine, tanilcipromine, reversible monoamino oxidase-A inhibitors (moclobemide, brofaromine, benzodiazepines (clonazepam, bromazepam, alprazolam and serotonin selective recaptors inhibitors - SSRI (paroxetine, sertraline, fluoxetine, fluvoxamine and some other drugs (venlafaxine, nefazodone, gabapentin, clonidine have been shown efficacy in several studies with different methodology. The tricyclic antidepressants ( imipramine, clomipramine, valproic acid and buspirone have shown negative results. Paroxetine is the most studied substance in double-blind trials with good results and well tolerated. Nowadays the individuals with social phobia can have a efficacious treatment to get an assertive behavior in social situations.

  6. The research of cognitive function in patients with schizophrenia%精神分裂症患者认知功能的研究

    Institute of Scientific and Technical Information of China (English)

    张艳

    2013-01-01

    精神分裂症患者认知功能的损害是其回归社会的重要影响因素。认知心理学为认知功能的评估提供了四方面的研究方法和途径。本综述以认知功能的评估方法为线索,从各种量表测查到返回抑制评定到功能核磁共振成像检查,再到成套的认知评估系统,使认知功能的研究越发有针对性。对精神分裂症患者认知功能障碍与其性别、病程、用药、阴性症状的关系进行了综述。慢性精神分裂症患者存在全面的认知功能损害,其认知功能损害无明显性别差异。使用非典型抗精神病药治疗的精神分裂症患者合并丁螺环酮组的认知功能与安慰剂组比较,仅在注意力方面有改善,且研究组在前3个月改善注意力的优势明显。精神分裂症患者长期住院治疗比非住院的患者或短时间住院治疗的患者认知损害严重。目前在治疗精神疾病认知功能损害方面较为新颖的治疗手段是关注5-HT1A受体。精神分裂症患者阴性症状严重的认知功能损害明显。%The cognitive impairment in schizophrenia patients was one of the important factors to affect them return to society.Cognitive psychology provided four sorts of research methods and approaches for cognitive function assessment.Following the cognitive function assessment,varieties of scales were performed from Inhibition of Return (IOR) to MRI,and then to complete cognitive function assessment system to make the research more targeted.In the paper,we reviewed the relationship of cognitive impairment in schizophrenia patients with sex,course of disease,taking medicine and negative symptoms.There was full of cognitive impairment in chronic schizophrenic patients,and the cognitive impairment had no obvious sex difference. The cognitive function in atypical antipsychotics combined with Buspirone group only had better improvement in attention than that in placebo group.The advantage was to

  7. 急性脑梗死抑郁症发生相关因素与预防分析%Analysis of Related Factors and Prevention of Depression in Patients With Acute Cerebral Infarction

    Institute of Scientific and Technical Information of China (English)

    郑容; 郭洛宁; 王芬

    2016-01-01

    目的:分析急性脑梗死抑郁症发生相关因素与预防。方法随机选取我院2013年3月~2016年3月收治的60例急性脑梗死抑郁症患者,将其作为研究组,选取60例急性脑梗死患者,将其作为对照组,即研究组(60例)和对照组(60例);给予研究组患者,应用丁螺环酮合并氟西汀治疗,根据汉密尔顿抑郁量表对临床患者的疗效进行评定,分析急性脑梗死抑郁症发生相关因素,并分析其预防措施。结果两组中,研究组与对照组比较,差异有统计学意义(P<0.05),可发现心理社会危险因素,会导致抑郁、焦虑,使患者血清 IL-6、TNF-α浓度升高,形成抑郁症,研究组经心理干预及药物治疗后,患者抑郁症状得到改善,治疗前后对比临床疗效显著(P<0.05)。结论在临床中,急性脑梗死抑郁症发生与患者神经功能缺失、性格内向、情绪不稳定、体验较多负性事件、社会支持低下有关,对患者采取药物治疗及心理干预,有助于改善患者抑郁症状,预防抑郁症形成。%Objective To analyze the related factors and prevention of depression in patients with acute cerebral infarction.Methods 60 cases of acute cerebral infarction patients with depression were randomly selected in our hospital from March 2013 to March 2016, as the study group, 60 cases of acute cerebral infarction patients were selected, as control group, that is, to study the group (60 cases) and control group (60 cases), give the study group patients, application with buspirone combined with lfuoxetine in the treatment of, according to Hamilton Depression Scale to the clinical therapeutic effects were assessed. Analysis of acute cerebral infarction depression related factors and analysis the preventive measures. Results In the two groups, the study group and the control group, there are differences (P<0.05), to find the psychological and social risk factors

  8. Infiniti 3000A 生物反馈仪治疗广泛性焦虑障碍的疗效%Infiniti 3000A biofeedback instrument in the treatment of generalized anxiety disorder

    Institute of Scientific and Technical Information of China (English)

    鲁晓波; 蒋从清; 刘忠纯

    2014-01-01

    目的:探讨 Infiniti 3000A 生物反馈仪对广泛性焦虑障碍患者的临床疗效。方法92例广泛性焦虑障碍患者随机分为实验组与对照组各46例,实验组治疗前后通过 Infiniti 3000A 生物反馈仪采集脑电、肌电、皮电等数值,然后以各种图像方式进行实时反馈放松治疗,1次/d,30 min/次;对照组口服丁螺环酮,10 mg/次,3次/d。2组均治疗6周,治疗前及治疗后第3、6周采用汉密尔顿焦虑量表(HAMA)、焦虑自评量表(SAS)和临床整体量表-疗效总评估量表(CGI-SI)评定2组治疗效果。结果治疗6周后,与治疗前相比,2组治疗指标参数均有所改善。2组 H AMA和SAS评分治疗3、6周与治疗前相比明显减少(P<0.05),2组间比较差异无统计学意义(P>0.05)。实验组有效率76%,对照组78%,2组比较差异无统计学意义(P>0.05)。结论 Infiniti 3000A 生物反馈仪对广泛性焦虑障碍患者的临床疗效显著,能较好地反馈放松患者的神经。%Objective To research the effect of Infiniti 3000A biofeedback instrument on patients with generalized anxiety disorder.Methods 92 patients with generalized anxiety disorder were randomly divided into experimental group (n=46)and control group (n=46).Experimental group acquired EEG,EMG and Bark wave by Infiniti 3000A biofeedback numerical in-strument before and after treatment,and then acquired the various image real-time feedback,biofeedback and relaxation therapy once a day,each time for 30 min;the control group received buspirone 10mg/time,3 times a day oral treatment.Two groups of patients were treated for 6 weeks.Before treatment and after treatment for 3 weeks and 6 weeks,Hamilton Anxiety Scale (HAMA),self-rating Anxiety Scale (SAS)and the clinical curative effect of the overall scale of total assessment scale (CGI-SI)were used to evaluate the clinical effectiveness of patients.Results After 6 weeks of treatment

  9. Irritable Bowel Syndrome.

    Science.gov (United States)

    Wald

    1999-02-01

    ; erythromycin, clarithromycin, and troleandomycin; some antidepressants; HIV protease inhibitors; and others. In patients with IBS with mild to moderate co-morbid depression, I have found that the use of SSRIs such as paroxetine, fluoxetine, or sertraline may be beneficial. It is important to tell patients that anxiety and disturbed sleep may occur during the first 10 days and benefits may not occur for 3 to 4 weeks. I prescribe a small amount of a short-acting benzodiazepine such as alprazolam, 0.5 mg two times per day, to control these symptoms. For generalized anxiety without depression, buspirone or clonazepam may be useful. I have found that patients who also have associated panic disorder may benefit from a benzodiazepine, tricyclic antidepressant, or an SSRI. However, these patients are best managed in conjunction with a psychiatrist or psychologist. I consider the use of alternative therapies in patients who fail to respond to conventional measures and who are receptive to alternative strategies. These include general relaxation techniques such as biofeedback and hypnosis therapies. PMID:11096567