Sample records for chlordiazepoxide

  1. Chlordiazepoxide

    Chlordiazepoxide is used to relieve anxiety and to control agitation caused by alcohol withdrawal. ... Darvon); propranolol (Inderal); rifampin (Rifadin); sedatives; sleeping pills; theophylline (Theo-Dur); tranquilizers; valproic acid (Depakene); and vitamins. ...

  2. Cost-effectiveness analysis of baclofen and chlordiazepoxide in uncomplicated alcohol-withdrawal syndrome

    Vikram K Reddy


    Full Text Available Objectives: Benzodiazepines (BZDs are the first-line drugs in alcohol-withdrawal syndrome (AWS. Baclofen, a gamma-aminobutyric acid B (GABA B agonist, controls withdrawal symptoms without causing significant adverse effects. The objective of this study was to compare the cost-effectiveness of baclofen and chlordiazepoxide in the management of uncomplicated AWS. Materials and Methods : This was a randomized, open label, standard controlled, parallel group study of cost-effectiveness analysis (CEA of baclofen and chlordiazepoxide in 60 participants with uncomplicated AWS. Clinical efficacy was measured by the Clinical Institute Withdrawal Assessment for alcohol (CIWA-Ar scores. Lorazepam was used as supplement medication if withdrawal symptoms could not be controlled effectively by the study drugs alone. Both direct and indirect medical costs were considered and the CEA was analyzed in both patient′s perspective and third-party perspective. Results : The average cost-effectiveness ratio (ACER in patient′s perspective of baclofen and chlordiazepoxide was Rs. 5,308.61 and Rs. 2,951.95 per symptom-free day, respectively. The ACER in third-party perspective of baclofen and chlordiazepoxide was Rs. 895.01 and Rs. 476.29 per symptom-free day, respectively. Participants on chlordiazepoxide had more number of symptom-free days when compared with the baclofen group on analysis by Mann-Whitney test (U = 253.50, P = 0.03. Conclusion : Both study drugs provided relief of withdrawal symptoms. Chlordiazepoxide was more cost-effective than baclofen. Baclofen was relatively less effective and more expensive than chlordiazepoxide.

  3. Continuous intravenous flumazenil infusion in a patient with chlordiazepoxide toxicity and hepatic encephalopathy

    Moh′d Al-Halawani


    Full Text Available Flumazenil, a benzodiazepine receptor antagonist, is the drug of choice for the diagnosis and treatment of benzodiazepine overdose. We are presenting a patient with chronic alcoholism and alcoholic liver disease, who came with alcohol withdrawal symptoms and treated chlordiazepoxide. Subsequently he developed a prolonged change in mental status that required treatment for benzodiazepine overdose and hepatic encephalopathy with flumazenil infusion for 28 days.

  4. Cost-effectiveness analysis of baclofen and chlordiazepoxide in uncomplicated alcohol-withdrawal syndrome

    Reddy, Vikram K.; Girish, K.; Pandit Lakshmi; R Vijendra; Ajay Kumar; Harsha, R.


    Objectives: Benzodiazepines (BZDs) are the first-line drugs in alcohol-withdrawal syndrome (AWS). Baclofen, a gamma-aminobutyric acid B (GABA B ) agonist, controls withdrawal symptoms without causing significant adverse effects. The objective of this study was to compare the cost-effectiveness of baclofen and chlordiazepoxide in the management of uncomplicated AWS. Materials and Methods : This was a randomized, open label, standard controlled, parallel group study of cost-effectiveness an...

  5. Cost-effectiveness analysis of baclofen and chlordiazepoxide in uncomplicated alcohol-withdrawal syndrome

    Reddy, Vikram K.; Girish, K.; Lakshmi, Pandit; R Vijendra; Kumar, Ajay; Harsha, R.


    Objectives: Benzodiazepines (BZDs) are the first-line drugs in alcohol-withdrawal syndrome (AWS). Baclofen, a gamma-aminobutyric acidB (GABAB) agonist, controls withdrawal symptoms without causing significant adverse effects. The objective of this study was to compare the cost-effectiveness of baclofen and chlordiazepoxide in the management of uncomplicated AWS. Materials and Methods: This was a randomized, open label, standard controlled, parallel group study of cost-effectiveness analysis (...

  6. New conventional coated-wire ion-selective electrodes for flow-injection potentiometric determination of chlordiazepoxide.

    Issa, Y M; Abdel-Ghani, N T; Shoukry, A F; Ahmed, Howayda M


    New chlordiazepoxide hydrochloride (Ch-Cl) ion-selective electrodes (conventional type) based on ion associates, chlordiazepoxidium-phosphomolybdate (I) and chlordiazepoxidium-phosphotungstate (II), were prepared. The electrodes exhibited mean slopes of calibration graphs of 59.4 mV and 60.8 mV per decade of (Ch-Cl) concentration at 25 degrees C for electrodes (I) and (II), respectively. Both electrodes could be used within the concentration range 3.16 x 10(-6)-1 x 10(-2) M (Ch-Cl) within the pH range 2.0-4.5. The standard electrode potentials were determined at different temperatures and used to calculate the isothermal coefficients of the electrodes, which were 0.00139 and 0.00093 V degrees C(-1) for electrodes (I) and (II), respectively. The electrodes showed a very good selectivity for Ch-Cl with respect to the number of inorganic cations, amino acids and sugars. The electrodes were applied to the potentiometric determination of the chlordiazepoxide ion and its pharmaceutical preparation under batch and flow injection conditions. Also, chlordiazepoxide was determined by conductimetric titrations. Graphite, copper and silver coated wires were prepared and characterized as sensors for the drug under investigation. PMID:16363470

  7. The chlordiazepoxide/pentylenetetrazol discrimination: characterization of drug interactions and homeostatic responses to drug challenges.

    Michaelis, R C; Holohean, A M; Criado, J R; Harland, R D; Hunter, G A; Holloway, F A


    Rats were trained to discriminate chlordiazepoxide (CDP) from pentylenetetrazol (PTZ) in a two-lever food motivated discrimination task. Training drug doses were adjusted until subjects emitted approximately 50% of their responses on each of the two drug-appropriate levers during saline injection tests. Tests that followed injection of CDP/PTZ combinations illustrated a reciprocal antagonism between the two drugs. Saline-injection tests that followed large dose injections of CDP revealed a period of predominantly PTZ-appropriate responding that persisted after the initial period of predominantly CDP-appropriate responding. These data are interpreted to suggest that, unlike some other drugs that have been shown to antagonize the behavioral and CNS effects of benzodiazepines, the interoceptive stimulus generated by PTZ occupies a position opposite to that of CDP along some single affective continuum. In addition, these data suggest that drug/drug (DD) discriminations are capable of characterizing the interactions between training drugs. Finally, the data suggest that the CDP/PTZ discrimination is a sensitive detector of bidirectional shifts in interoceptive stimulus state along the CDP/PTZ continuum. PMID:3147473

  8. Gabra5-gene haplotype block associated with behavioral properties of the full agonist benzodiazepine chlordiazepoxide.

    Clément, Y; Prut, L; Saurini, F; Mineur, Y S; Le Guisquet, A-M; Védrine, S; Andres, C; Vodjdani, G; Belzung, C


    The gabra5 gene is associated with pharmacological properties (myorelaxant, amnesic, anxiolytic) of benzodiazepines. It is tightly located (0.5 cM) close to the pink-eyed dilution (p) locus which encodes for fur color on mouse chromosome 7. We tested the putative role of the gabra5 gene in pharmacological properties of the full non specific agonist chlordiazepoxide (CDP), using behavioral and molecular approaches in mutated p/p mice and wild type F2 from crosses between two multiple markers inbred strain ABP/Le and C57BL/6By strain. From our results, using rotarod, light-dark box, elevated maze and radial arm maze tests, we demonstrate that p/p mice are more sensitive than WT to the sensory motor, anxiolytic and amnesic effect of CDP. This is associated with the presence of a haplotypic block on the murine chromosome 7 and with an up regulation of gabra5 mRNAs in hippocampi of p/p F2 mice. PMID:22677273

  9. Preconcentration and determination of chlordiazepoxide and diazepam drugs using dispersive nanomaterial-ultrasound assisted microextraction method followed by high performance liquid chromatography.

    Pebdani, A Amiri; Khodadoust, S; Talebianpoor, M S; Zargar, H R; Zarezade, V


    Benzodiazepines (BDs) are used widely in clinical practice, due to their multiple pharmacological functions. In this study a dispersive nanomaterial-ultrasound assisted- microextraction (DNUM) method followed by high performance liquid chromatography (HPLC) was used for the preconcentration and determination of chlordiazepoxide and diazepam drugs from urine and plasma samples. Various parameters such as amount of adsorbent (mg: ZnS-AC), pH and ionic strength of sample solution, vortex and ultrasonic time (min), and desorption volume (mL) were investigated by fractional factorial design (FFD) and central composite design (CCD). Regression models and desirability functions (DF) were applied to find the best experimental conditions for providing the maximum extraction recovery (ER). Under the optimal conditions a linear calibration curve were obtained in the range of 0.005-10μgmL(-1) and 0.006-10μgmL(-1) for chlordiazepoxide and diazepam, respectively. To demonstrate the analytical performance, figures of merits of the proposed method in urine and plasma spiked with chlordiazepoxide and diazepam were investigated. The limits of detection of chlordiazepoxide and diazepam in urine and plasma were ranged from 0.0012 to 0.0015μgmL(-1), respectively. PMID:26655106

  10. Simultaneous HPLC Determination of Chlordiazepoxide and Mebeverine HCl in the Presence of Their Degradation Products and Impurities

    Rania N. El-Shaheny


    Full Text Available A simple, rapid, and sensitive RP-HPLC method was developed and validated for the simultaneous determination of chlordiazepoxide (CDO and mebeverine HCl (MBV in the presence of CDO impurity (2-amino-5-chlorobenzophenone, ACB and MBV degradation product (veratric acid, VER. Separation was achieved within 9 min on a BDS Hypersil phenyl column (4.5 mm × 250 mm, 5 µm particle size using a mobile phase consisting of acetonitrile: 0.1 M potassium dihydrogen phosphate: triethylamine (35 : 65 : 0.2, v/v/v in an isocratic mode at a flow rate of 1 mL/min. The pH of the mobile phase was adjusted to 4.5 with orthophosphoric acid and UV detection was set at 260 nm. A complete validation procedure was conducted. The proposed method exhibited excellent linearity over the concentration ranges of 1.0–100.0, 10.0–200.0, 2.0–40.0, and 2.0–40.0 µg/mL for CDO, MBV, VER, and ACB, respectively. The proposed method was applied for the simultaneous determination of CDO and MBV in their coformulated tablets with mean percentage recoveries of 99.75 ± 0.62 and 98.61 ± 0.38, respectively. The results of the proposed method were favorably compared with those of a comparison HPLC method using Student t-test and the variance ratio F-test. The chemical structure of MBV degradation product was ascertained by mass spectrometry and IR studies.

  11. Chlordiazepoxide and Clidinium

    ... worsen your condition and cause withdrawal symptoms (anxiousness, sleeplessness, and irritability). Your doctor probably will decrease your ... include: upset stomach drowsiness weakness or tiredness excitement sleeplessness dry mouth heartburn bloated feeling eyes more sensitive ...

  12. Septal co-infusions of glucose with the benzodiazepine agonist chlordiazepoxide impair memory, but co-infusions of glucose with the opiate morphine do not

    Krebs-Kraft, Desiree L.; Parent, Marise B.


    We have found repeatedly that medial septal (MS) infusions of glucose impair memory when co-infused with the γ-amino butyric acid (GABA) agonist muscimol. The present experiment sought to determine whether the memory-impairing effects of this concentration of glucose would generalize to another GABAA receptor agonist and to an agonist from another neurotransmitter system that is known to impair memory. Specifically, we determined whether the dose of glucose that produces memory deficits when ...

  13. A validated method for simultaneous screening and quantification of twenty-three benzodiazepines and metabolites plus zopiclone and zaleplone in whole blood by liquid-liquid extraction and ultra-performance liquid chromatography- tandem mass spectrometry

    Simonsen, Kirsten Wiese; Hermansson, Sigurd; Steentoft, Anni;


    cases and living persons. The detected compounds were alprazolam, bromazepam, brotizolam, chlordiazepoxide, demoxepam, clobazam, clonazepam, 7-aminoclonazepam, diazepam, nordiazepam, estazolam, flunitrazepam, 7-aminoflunitrazepam, lorazepam, lormetazepam, midazolam, nitrazepam, 7-aminonitrazepam...

  14. Phenobarbital compared to benzodiazepines in alcohol withdrawal treatment

    Askgaard, Gro; Hallas, Jesper; Fink-Jensen, Anders; Molander, Anna Camilla; Madsen, Kenneth Grønkjær; Pottegård, Anton


    BACKGROUND: Long-acting benzodiazepines such as chlordiazepoxide are recommended as first-line treatment for alcohol withdrawal. These drugs are known for their abuse liability and might increase alcohol consumption among problem drinkers. Phenobarbital could be an alternative treatment option......, possibly with the drawback of a more pronounced acute toxicity. We evaluated if phenobarbital compared to chlordiazepoxide decreased the risk of subsequent use of benzodiazepines, alcohol recidivism and mortality. METHODS: The study was a register-based cohort study of patients admitted for alcohol...... withdrawal 1998-2013 and treated with either phenobarbital or chlordiazepoxide. Patients were followed for one year. We calculated hazard ratios (HR) for benzodiazepine use, alcohol recidivism and mortality associated with alcohol withdrawal treatment, while adjusting for confounders. RESULTS: A total of...

  15. GABA Enhancement of Maternal Defense in Mice: Possible Neural Correlates

    Lee, Grace; Gammie, Stephen C.


    Previous studies have shown that low doses of GABAA receptor agonists facilitate maternal defense of offspring (maternal aggression), without significantly affecting other maternal behaviors. In addition, it has been demonstrated that endogenous changes in GABAergic neurotransmission occur in association with lactation. This study investigated the effects of GABAA receptor agonist, chlordiazepoxide (CDP), a benzodiazepine (BDZ), on maternal behaviors including aggression, and identified brain...

  16. [Neurochemical characteristics of the ventromedial hypothalamus and anti-aversive effects of anxiolytic agents in various anxiety models].

    Talalaenko, A N; Pankrat'ev, D V; Goncharenko, N V


    Neurochemical analysis using anxiosedative and anxioselective agents injected into the hypothalamus revealed that antiaversive action of camprione is only realised under conditions of domineering fear motivation whereas that of chlordiazepoxide, phenibut, indoter may also be realised under conditions of negative stressful zoo-social impacts mediated by serotonin. PMID:11763535

  17. Neuroprotective effects of anticonvulsants in rat hippocampal slice cultures exposed to oxygen/glucose deprivation

    Rekling, Jens C


    ). Hippocampal slice cultures were submitted to 1 h OGD and the resulting cell death was quantified 24 h later using a novel automated fluorescent scanning method. The classical anticonvulsants phenobarbital, phenytoin, ethosuximide, chlordiazepoxide and midazolam all significantly and dose-dependently reduced...

  18. Alcohol Withdrawal Syndrome: Symptom-Triggered versus Fixed-Schedule Treatment in an Outpatient Setting

    Elholm, B.; Larsen, Klaus; Hornnes, N.;


    Aims: To investigate whether, in the treatment with chlordiazepoxide for outpatient alcohol withdrawal, there are advantages of symptom-triggered self-medication over a fixed-schedule regimen. Methods: A randomized controlled trial in outpatient clinics for people suffering from alcohol dependence...... (AD) and alcohol-related problems; 165 adult patients in an outpatient setting in a specialized alcohol treatment unit were randomized 1:1 to either a symptom-triggered self-medication or tapered dose, using chlordiazepoxide. Alcohol withdrawal symptoms, amount of medication, duration of symptoms...... the 1-year follow-up. Results: We found no differences in the quantity of medication consumed, time to relapse, well being or treatment satisfaction. Conclusion: Symptom-triggered self-medication was as safe as fixed-schedule medication in treating outpatients with AD and mild to moderate symptoms of...

  19. [Neurochemical analysis of the amygdala basolateral nucleus of rats during anxiety tests].

    Talalaenko, A N; Babiĭ, Iu V; Perch, N N; Vozdvigin, S A; Panfilov, V Iu


    Chlordiazepoxid, phenibut, indoter, campiron, campironin, when administered into the amygdala, improve the anxiety condition of rats in avoidance tests and resemble by their effects dophamine, GABA, or serotonin. Observed differences in the anxiolytic effects between anxiosedative and anxioselective agents seem to be due to an unequal contribution of the monoamin- and aminoacidotergic transmitters into the mechanisms of heteromodal aversive anxiety genesis in the basolateral area of the amygdalar complex. PMID:12436687

  20. Attenuation of alcohol withdrawal syndrome and blood cortisol level with forced exercise in comparison with diazepam.

    Majid Motaghinejad; Mohammad Yasan Bangash; Ozra Motaghinejad


    Relieving withdrawal and post-abstinence syndrome of alcoholism is one of the major strategies in the treatment of alcohol addicted patients. Diazepam, chlordiazepoxide, and topiramate are the approved medications that were used for this object. To assess the role of non-pharmacologic therapy in the management of alcohol withdrawal syndrome, we analyzed effects of forced exercise by treadmill on alcohol dependent mice as an animal model. A total of 60 adult male mice were divided into 5 group...

  1. An animal model of the interpersonal communication of interoceptive (private) states.

    Lubinski, D; Thompson, T


    Pigeons were taught to interact communicatively (i.e., exchange discriminative stimuli) based on 1 pigeon's internal state, which varied as a function of cocaine, pentobarbital, and saline administration. These performances generalized to untrained pharmacological agents (d-amphetamine and chlordiazepoxide) and were observed in the absence of aversive stimulation, deprivation, and unconditioned reinforcement. The training procedure used in this study appears similar to that by which humans le...

  2. Alcohol detoxification in Ysbyty Gwynedd: Two small sips or one big gulp? Two-step screening more reliable for identification of alcohol dependency syndrome at risk of delirium tremens for routine care

    Salman, Muhammad; Subbe, Christian


    Compliance with pathways for hospitalised patients with alcohol dependency syndrome is often poor. A pathway for recognition and treatment of alcohol dependency was redesigned as part of a 12 month service improvement project in the acute medical unit using plan, do, study, act (PDSA) cycles. A needs assessment was undertaken: Audit data from 2013 showed over-prescription of chlordiazepoxide for detoxification treatment (DT) leading to prolonged hospital admissions with an average length of s...

  3. Sedation and disruption of maternal motivation underlie the disruptive effects of antipsychotic treatment on rat maternal behavior

    Zhao, Changjiu; Li, Ming


    The behavioral mechanisms underlying antipsychotic-induced maternal behavior deficits were examined in the present study. Different groups of postpartum rats were treated with haloperidol (0.1 mg/kg), clozapine (10.0 mg/kg), chlordiazepoxide (5.0 mg/kg, an anxiolytic) or vehicle (0.9% saline) on Days 4 and 6 postpartum and their maternal behaviors were tested under either pup-separation (e.g. pups were removed from their mothers for 4 h before testing) or no-pup-separation condition. Maternal...

  4. Cyclic adenosine monophosphate phosphodiesterase in brain: effect on anxiety.

    Beer, B; Chasin, M; Clody, D E; Vogel, J R


    Drugs that reduce anxiety may be mediated by cyclic adenosine monophosphate in the brain because (i) potent anxiety-reducing drugs are also potent inhibitors of brain phosphodiesterase activity; (ii) dibutyryl cyclic adenosine monophosphate has the ability to reduce anxiety; (iii) the methylxanthines show significant anxiety-reducing effects; (iv) theophylline and chlordiazepoxide produce additive anxiety-reducing activity; and (v) there is a significant correlation between the anxiety-reducing property of drugs and their ability to inhibit phosphodiesterase activity in the brain. PMID:4402069

  5. Derivative spectrophotometry as a tool for the determination of drug partition coefficients in water/dimyristoyl-L-alpha-phosphatidylglycerol (DMPG) liposomes.

    Rodrigues, C; Gameiro, P; Reis, S; Lima, J L; de Castro, B


    The partition coefficients (K(p)) between lipid bilayers of dimyristoyl-L-alpha-phosphatidylglycerol (DMPG) unilamellar liposomes and water were determined using derivative spectrophotometry for chlordiazepoxide (benzodiazepine), isoniazid and rifampicin (tuberculostatic drugs) and dibucaine (local anaesthetic). A comparison of the K(p) values in water/DMPG with those in water/DMPC (dimyristoyl-L-alpha-phosphatidylcholine) revealed that for chlordiazepoxide and isoniazid, neutral drugs at physiological pH, the partition coefficients are similar in anionic (DMPG) and zwitterionic (DMPC) liposomes. However, for ionised drugs at physiological pH, the electrostatic interactions are different with DMPG and DMPC, with the cationic dibucaine having a stronger interaction with DMPG, and the anionic rifampicin having a much larger K(p) in zwitterionic DMPC. These results show that liposomes are a better model membrane than an isotropic two-phase solvent system, such as water-octanol, to predict drug-membrane partition coefficients, as they mimic better the hydrophobic part and the outer polar charged surface of the phospholipids of natural membranes. PMID:11744194

  6. Effects of several benzodiazepines, alone and in combination with flumazenil, in rhesus monkeys trained to discriminate pentobarbital from saline.

    Woolverton, W L; Nader, M A


    The purpose of the present study was to further investigate the relationship between the DS effects of PB and those of benzodiazepines (BZs) and to begin to collect pharmacological information concerning receptor mechanisms involved in this behavioral effect of BZs. Rhesus monkeys (n = 3), trained to discriminate pentobarbital (PB; 10 mg/kg, IG) from saline under a discrete-trials shock avoidance procedure, were given IG diazepam (0.3-10 mg/kg), chlordiazepoxide (1.0-30 mg/kg), or etizolam (0.3-10 mg/kg) alone and in combination with flumazenil (0.01-1.7 mg/kg, IM). Flumazenil was administered 10 min prior to the administration of saline, PB or the BZs. All three BZs fully substituted for PB in all monkeys. Diazepam was the most potent with a mean ED50 of 0.81 mg/kg (SEM = 0.04) while chlordiazepoxide was the least potent (mean ED50 = 5.78 mg/kg, SEM = 1.22 mg/kg). The ED50 for etizolam was 1.22 mg/kg (SEM = 0.37 mg/kg). Pretreatment with flumazenil (0.01-1.0 mg/kg) resulted in a dose-related parallel shift to the right in the dose-response function for PB-appropriate responding in all monkeys for all three BZs. The mean (n = 3) pKB value with 0.1 mg/kg flumazenil was 6.51 (SEM = 0.42) for diazepam and 6.57 (SEM = 0.17) for chlordiazepoxide. This value could not be calculated for etizolam because only one monkey was tested with 0.1 mg/kg flumazenil. However, the mean pKB for etizolam considering all monkeys and all doses of flumazenil was 6.58 (SEM = 0.47). Apparent pA2 values for flumazenil with diazepam were 6.02 for one monkey and 7.11 for another. All three BZs tended to increase average latency to respond. Apparent pKB and pA2 analysis may prove useful for elucidating receptor mechanisms involved in the behavioral effects of BZs. PMID:8748392

  7. Effect of the new antiepileptic drug retigabine in a rodent model of mania

    Dencker, Ditte; Dias, Rebecca; Pedersen, Mette Lund;


    Bipolar spectrum disorders are severe chronic mood disorders that are characterized by episodes of mania or hypomania and depression. Because patients with manic symptoms often experience clinical benefit from treatment with anticonvulsant drugs, it was hypothesized that retigabine, a novel...... compound with anticonvulsant efficacy, may also possess antimanic activity. The amphetamine (AMPH)+chlordiazepoxide (CDP)-induced hyperactivity model has been proposed as a suitable model for studying antimanic-like activity of novel compounds in mice and rats. The aims of the present study in rats were......, significantly and dose-dependently attenuates the induced hyperactivity at a lowest effective dose of 1.0 mg/kg, whereas basal locomotor activity is reduced only at doses 4.0 mg/kg. In conclusion, retigabine was found to have an antimanic-like effect in the AMPH+CDP-induced hyperactivity model, suggesting a...

  8. [Neurochemical mechanisms of dorsal pallidum in antiadverse effects of anxiolytics of different models of anxiety].

    Talaenko, A N; Krivobok, G K; Pankrat'ev, D V; Goncharenko, N V


    Microinjections of glutamine acid, serotonine and campiron into globus pallidus reveal antiadverse properties of ratsin in the test with avoiding "threatening situation" but not with "illuminated site" under the conditions of rats' free choice between light and dark sites. Dopamine, apomorphine, GABA, chlordiazepoxide, phenibut and indoter injected locally into this formation of basal ganglia do not affect the mechanisms of the involuntary movement, but counteract the conditions of anxiety in both models of behaviour. These results show different functional role of monoamino- and aminoacidergic systems of dorsal pallidum in operative regulation of behaviour with changing of aversive stimulus modality. Preliminary intraperitoneal injection of functional antagonists of investigated synoptotropic followed by microinjection of monoamines and amino acids into globus pallidus reveal selective involvement of neuromediator systems of dorsal pallidum into antiadverse anxiosedative and anxioselective actions. PMID:16206621

  9. [Neurochemical features of the ventral pallidum in realization of the antiaversive effects of anxiolytics in different models of anxiety].

    Talalaenko, A N; Pankrat'ev, D V; Bulgakova, N P


    Preliminary intraperitoneal injections of some combinations of adreno- and dopaminomimetics, monoamines, and mediator amino acids (as well as of their agonists and antagonists) followed by microinjections of the same combinations into the ventral pallidum reveal differences in the functional significance of the neurochemical profile of this paleostriatum formation in realization of the anxiety states of different genesis, as manifested in the "illuminated site avoidance" and the "threatening situation" tests in rats. The pharmacological analysis based on the local injection of anxiosedative and anxioselective agents into the ventral paleostriatum showed that the antiaversive action of campirone is revealed under the conditions of dominating fear motivation, while that analogous action of chlordiazepoxide, phenibut and indoter is revealed under negative stressful zoosocial impacts and is realized by serotonin- and GABA-ergic (rather than by cathecholamine- and glutaminergic) aversive systems of the ventral pallidum. PMID:16579051

  10. [A decreased frequency of peeking out from the dark compartment--the only constant index of the effect of anxiogens on the behavior of mice in a "light-darkness" chamber].

    Lapin, I P


    Special measurements of the effects of anxiolytics and anxiogens on the commonly used parameters of behavior of mice in a dark-light chamber (the rate of transitions and time spent in a dark and light compartments) demonstrated their low reproducibility in consecutive experiments. Therefore, these indices are not reliable (Lapin, 1992). One more parameter was tested in the present study. A decrease in the rate of leanings out of the dark compartment appeared to be a constant effect of standard anxiety-inducing drugs: caffeine, pentylenetetrazole, yohimbine, and a putative endogenous anxiogen phenylethylamine. Increase in the rate of leanings out, like increase in the rate of transitions and shortening of the time spent in a dark compartment produced by anxiolytics diazepam, chlordiazepoxide, hydroxyzine, phenibut and baclofen were not significant in the majority of experiments. That is why these effects of anxiolytics are not reliable for measuring the activity of anxiolytics in a dark-light chamber. PMID:10420565

  11. Neurochemical mechanisms of the dorsal pallidum in the antiaversive effects of anxiolytics in various models of anxiety.

    Talalaenko, A N; Krivobok, G K; Pankrat'ev, D V; Goncharenko, N V


    In conditions in which rats had a free choice between dark and light chambers, microinjections of glutamic acid, serotonin, and campiron into the globus pallidus showed that these agents have antiaversive properties in a threatening situation test but not in an illuminated area test. Dopamine, apomorphine, GABA, chlordiazepoxide, phenibut, and indoter injected locally into this formation of the basal ganglia had no effect on the mechanisms of voluntary movement but counteracted anxiety states in both behavioral models. These results provide evidence that the monoaminergic and aminoacidergic systems of the dorsal pallidum have different functional roles in the operative regulation of behavior for aversive stimuli of different modalities. Prior intraperitoneal administration of functional antagonists of these synaptotropic substances and subsequent microinjection of transmitter monoamines and amino acids and their agonists into the globus pallidus demonstrated the selective involvement of the neurotransmitter systems of the dorsal pallidum in the antiaversive effects of anxiosedative and anxioselective substances. PMID:16841156

  12. Neurochemical characteristics of the ventromedial hypothalamus in mediating the antiaversive effects of anxiolytics in different models of anxiety.

    Talalaenko, A N; Pankrat'ev, D V; Goncharenko, N V


    In experiments on rats using an "illuminated area" avoidance test and a "threatening situation" avoidance test, preliminary i.p. administration and subsequent microinjection into the ventromedial hypothalamus of various combinations of monoamines, transmitter amino acids, and their agonists and antagonists demonstrated differences in the functional importance of the neurochemical profile of this limbic formation in mediating anxiety states of different origins. The neurochemical analysis with local intrahypothalamic administration of anxiosedative and anxioselective substances showed that the antiaversive actions of Campirone are obtained only in conditions in which the dominant motivation is fear, while chlordiazepoxide, Phenibut, and Indoter are also active in anxiety induced by negatively stressful zoosocial influences; these actions are mediated respectively by serotoninergic and GABAergic types of synaptic switching in the ventromedial hypothalamus. PMID:12762592

  13. Voltammetric analysis of N-containing drugs using the hanging galinstan drop electrode (HGDE).

    Channaa, H; Surmann, P


    The electrochemical behaviour of several N-containing voltammetric active drugs such as 1,4-benzodiazepines (chlordiazepoxide, nitrazepam and diazepam) as well as one nitro-compound (nitrofurantoin) and one azo-compound (phenazopyridine) is described using a new kind of liquid electrode, the hanging galinstan drop electrode. Concentrations of 10(-5) - 10(-8) mol L(-1) are generally measurable. Differential pulse and adsorptive stripping voltammograms are recorded in different supporting electrolytes, like 0.1 M KNO3, acetate buffer solution pH = 4.6 and phosphate buffer solution pH = 7.0. The effects of varying the starting potentials, U(start) for DPV and accumulation times, t(acc) for AdSV are considered. Briefly, it is shown that the novel galinstan electrode is suitable for reducing several functional groups in organic substances, here presented for N-oxide-, azomethine-, nitro- and azo-groups. PMID:19348337

  14. Pharmacological characterisation of a modified social interaction model of anxiety in the rat.

    Guy, A P; Gardner, C R


    Social interaction (SI) between two unfamiliar male rats in a dimly lit, familiar environment has been investigated as a model of anxiety, where novelty of the partner remains as the principal anxiogenic stimulus. A range of centrally acting drugs have been tested in this situation. Chlordiazepoxide, nitrazepam, flunitrazepam, and flurazepam all increase SI, as does buspirone, CL 218872, suriclone, sodium valproate, and nicotinamide in the model described. Anxiogenic agents FG 7142 and yohimbine reduced SI without significant modification of motor activities. However, the stimulant amphetamine increased all behaviours in this condition. Amphetamine also increased all behaviours when rats were tested with their cagemates, when the desire for SI is largely satiated. CL 218872 also increased SI in this second situation, and it is suggested that this agent may have a non-specific component in its action in this test. Additionally, caffeine, theophylline, and piracetam may also have non-specific behavioural actions in this model. PMID:2864655


    Wahlang JB


    Full Text Available Fixed drug eruption (FDE is common type of drug eruption seen in skin clinics. FDE usually occurs within hours of administration of the offending agent. Most commonly implicated are sulphonamides, salicylates, oxyphenbutazones, tetracycline, dapsone, chlordiazepoxide, barbiturates, phenolphthalein, morphine, codeine,quinine and derivatives, phenacetin, erythromycin, griseofulvin, mebendazole, meprobamate etc. We hereby report a case of fixed drug eruption on glans penis due to metronidazole, a nitroimidazole-derivative clinically indicated in trichomoniasis, amebiasis, giardiasis, anaerobic and mixed antibacterial infections. A patientadministered metronidazole IV developed erythematous superficial non-tender ulceration over the glans penis on the second day of treatment with Inj. Metronidazole. A provisional diagnosis of metronidazole induced fixed drug eruption was made, metronidazole inj. was stopped and the patient was managed with Tab. Prednisolone30mg/day tapered over 10 days and Fusidic acid+Betamethasone cream.

  16. Interaction of tricyclic antidepressants with cholestyramine in vitro.

    Bailey, D N; Coffee, J J; Anderson, B; Manoguerra, A S


    The adsorption of amitriptyline, desipramine, doxepin, imipramine, and nortriptyline onto cholestyramine was demonstrated in vitro with use of 1.2 mol/L HCl at 37 degrees C to simulate gastric fluid. Binding to cholestyramine was approximately 80% for each of the tricyclic antidepressants, and this was about the same degree of binding noted with a nonpharmaceutical, non-ionic resin widely used in the diagnostic toxicology laboratory (Amberlite XAD-2). In contrast, five other non-antidepressants (acetaminophen, chlordiazepoxide, procainamide, quinidine, and theophylline) showed only minimal binding to cholestyramine under these conditions. Activated charcoal completely bound all drugs studied. These findings suggest that cholestyramine should be used with caution in patients receiving tricyclic antidepressants. They also suggest that cholestyramine may be a potentially useful adjunctive therapy in treatment of overdose with the tricyclic antidepressants. PMID:1519310

  17. Reinforcement magnitude modulation of rate dependent effects in pigeons and rats.

    Ginsburg, Brett C; Pinkston, Jonathan W; Lamb, R J


    Response rate can influence the behavioral effects of many drugs. Reinforcement magnitude may also influence drug effects. Further, reinforcement magnitude can influence rate-dependent effects. For example, in an earlier report, we showed that rate-dependent effects of two antidepressants depended on reinforcement magnitude. The ability of reinforcement magnitude to interact with rate-dependency has not been well characterized. It is not known whether our previous results are specific to antidepressants or generalize to other drug classes. Here, we further examine rate-magnitude interactions by studying effects of two stimulants (d-amphetamine [0.32-5.6 mg/kg] and cocaine [0.32-10 mg/kg]) and two sedatives (chlordiazepoxide [1.78-32 mg/kg] and pentobarbital [1.0-17.8 mg/kg]) in pigeons responding under a 3-component multiple fixed-interval (FI) 300-s schedule maintained by 2-, 4-, or 8-s of food access. We also examine the effects of d-amphetamine [0.32-3.2 mg/kg] and pentobarbital [1.8-10 mg/kg] in rats responding under a similar multiple FI300-s schedule maintained by 2- or 10- food pellet (45 mg) delivery. In pigeons, cocaine and, to a lesser extent, chlordiazepoxide exerted rate-dependent effects that were diminished by increasing durations of food access. The relationship was less apparent for pentobarbital, and not present for d-amphetamine. In rats, rate-dependent effects of pentobarbital and d-amphetamine were not modulated by reinforcement magnitude. In conclusion, some drugs appear to exert rate-dependent effect which are diminished when reinforcement magnitude is relatively high. Subsequent analysis of the rate-dependency data suggest the effects of reinforcement magnitude may be due to a diminution of drug-induced increases in low-rate behavior that occurs early in the fixed-interval. PMID:21707192

  18. Drug discrimination under two concurrent fixed-interval fixed-interval schedules.

    McMillan, D E; Li, M


    Pigeons were trained to discriminate 5.0 mg/kg pentobarbital from saline under a two-key concurrent fixed-interval (FI) 100-s FI 200-s schedule of food presentation, and later tinder a concurrent FI 40-s FI 80-s schedule, in which the FI component with the shorter time requirement reinforced responding on one key after drug administration (pentobarbital-biased key) and on the other key after saline administration (saline-biased key). After responding stabilized under the concurrent FI 100-s FI 200-s schedule, pigeons earned an average of 66% (after pentobarbital) to 68% (after saline) of their reinforcers for responding under the FI 100-s component of the concurrent schedule. These birds made an average of 70% of their responses on both the pentobarbital-biased key after the training dose of pentobarbital and the saline-biased key after saline. After responding stabilized under the concurrent FI 40-s FI 80-s schedule, pigeons earned an average of 67% of their reinforcers for responding under the FI 40 component after both saline and the training dose of pentobarbital. These birds made an average of 75% of their responses on the pentobarbital-biased key after the training dose of pentobarbital, but only 55% of their responses on the saline-biased key after saline. In test sessions preceded by doses of pentobarbital, chlordiazepoxide, ethanol, phencyclidine, or methamphetamine, the dose-response curves were similar under these two concurrent schedules. Pentobarbital, chlordiazepoxide, and ethanol produced dose-dependent increases in responding on the pentobarbital-biased key as the doses increased. For some birds, at the highest doses of these drugs, the dose-response curve turned over. Increasing doses of phencyclidine produced increased responding on the pentobarbital-biased key in some, but not all, birds. After methamphetamine, responding was largely confined to the saline-biased key. These data show that pigeons can perform drug discriminations under concurrent

  19. The effect of mGlu8 deficiency in animal models of psychiatric diseases.

    Fendt, M; Bürki, H; Imobersteg, S; van der Putten, H; McAllister, K; Leslie, J C; Shaw, D; Hölscher, C


    The metabotropic glutamate receptor subtype 8 (mGlu(8)) is presynaptically located and regulates the release of the transmitter. Dysfunctions of this mechanism are involved in the pathophysiology of different psychiatric disorders. mGlu(8) deficient mice have been previously investigated in a range of studies, but the results are contradictory and there are still many open questions. Therefore, we tested mGlu(8)-deficient animals in different behavioral tasks that are commonly used in neuropsychiatric research. Our results show a robust contextual fear deficit in mGlu(8)-deficient mice. Furthermore, novel object recognition, chlordiazepoxide-facilitated extinction of operant conditioning and the acoustic startle response were attenuated by mGlu(8) deficiency. We found no changes in sensory processing, locomotor activity, prepulse inhibition, phencyclidine-induced changes in locomotion or prepulse inhibition, operant conditioning, conditioned fear to a discrete cue or in animal models of innate fear and post-traumatic stress disorder. We conclude that mGlu(8) might be a potential target for disorders with pathophysiological changes in brain areas where mGlu(8) modulates glutamate and gamma-amino butyric acid (GABA) transmission. Our data especially point to anxiety disorders involving exaggerated contextual fear, such as generalized anxiety disorders, and to conditions with disturbed declarative memory. PMID:19740090

  20. Alcohol detoxification in Ysbyty Gwynedd: Two small sips or one big gulp? Two-step screening more reliable for identification of alcohol dependency syndrome at risk of delirium tremens for routine care

    Salman, Muhammad; Subbe, Christian


    Compliance with pathways for hospitalised patients with alcohol dependency syndrome is often poor. A pathway for recognition and treatment of alcohol dependency was redesigned as part of a 12 month service improvement project in the acute medical unit using plan, do, study, act (PDSA) cycles. A needs assessment was undertaken: Audit data from 2013 showed over-prescription of chlordiazepoxide for detoxification treatment (DT) leading to prolonged hospital admissions with an average length of stay of 5.5 days in 2012/2013. Acceptability of screening tools was tested: Common screening tools (CEWA, AUDIT) were rejected by junior doctors due to the high number of questions as too cumbersome for routine practice. Compliance with usage in random samples over a three month period was persistently (n=10%. Testing of an abbreviated AUDIT questionnaire with only two questions and a specified threshold showed a AUROC of 1 (p<0.001 for correct identification). The screening tool was implemented in several PDSAs cycles. After the final cycle a random sample of 100 patients was reviewed for pathway compliance over a three months period. Eighty-six patients were screened with the two-question tool of these 18 were identified as possible risk. Of these 16 patients had the full AUDIT questionnaire, only eight with elevated values were started on DT. Overall compliance with the pathway increased to 84%. PMID:26734413

  1. The discriminative stimulus properties of ethanol and acute ethanol withdrawal states in rats.

    Gauvin, D V; Harland, R D; Criado, J R; Michaelis, R C; Holloway, F A


    Twelve male Sprague-Dawley rats were trained in a standard two-choice Drug 1-Drug 2 discrimination task utilizing 3.0 mg/kg chlordiazepoxide (CDP, an anxiolytic drug) and 20 mg/kg pentylenetetrazol (PTZ, an anxiogenic drug) as discriminative stimuli under a VR 5-15 schedule of food reinforcement. Saline tests conducted at specific time points after acute high doses of ethanol (3.0 and 4.0 g/kg) indicated a delayed rebound effect, evidenced by a shift to PTZ-appropriate responding. Insofar as such a shift in lever selection indexes a delayed anxiety-like state, this acute 'withdrawal' reaction can be said to induce an affective state similar to that seen with chronic ethanol withdrawal states. Ethanol generalization tests: (1) resulted in a dose- and time-dependent biphasic generalization to CDP, (2) failed to block the PTZ stimulus and (3) failed to block the time- and dose-dependent elicitation of an ethanol-rebound effect. These data suggest that ethanol's anxiolytic effects are tenuous. PMID:2791886

  2. Olfactory bulb ablation in the rat: behavioural changes and their reversal by antidepressant drugs.

    van Riezen, H; Schnieden, H; Wren, A F


    1. The effects of bilateral olfactory bulbectomy, sham-operation and inducement of peripheral anosmia were studied on locomotor activity, passive avoidance acquisition and irritability. 2. Bulbectomized rats were hyperactive, deficient at learning a step-down passive avoidance response and hyperirritable. Peripheral anosmia, induced by intranasal infusion of ZnSO4 solution resulted in no behavioural changes. 3. Chronic pretreatment with amitriptyline (3 and 10 mg/kg) and a tetracyclic antidepressant mianserin (Org GB 94, 5 and 15 mg/kg) reversed the hyperactivity and reduced the learning deficit of bulbectomized rats. These drugs had no significant effects on sham-operated animals. 4. Neither amitriptyline nor mianserin reduced the exaggerated responses of bulbectomized rats to external stimuli. 5. (+)-Amphetamine (1 and 3 mg/kg) accelerated the acquisition of the passive avoidance response, greatly enhanced the locomotor activity and slightly increased the irritability score of both sham-operated and bulbectomized rats. 6. Chlorpromazine (1 and 3 mg/kg) and chlordiazepoxide (10 mg/kg) significantly reduced the acquisition, locomotor activity and irritability of experimental and control rats. 7. Lithium sulphate (1 and 3 mg/kg) had no effect on activity or irritability but produced a small impairment in acquistion of bulbectomized rats. 8. It is concluded that the reversal by antidepressant drugs of the behavioural syndrome seen after olfactory bulb ablation could constitute a new model for the detection of this group of centrally acting compounds. PMID:907867

  3. Simultaneous determination of twelve benzodiazepines in human serum using a new reversed-phase chromatographic column on a 2-microns porous microspherical silica gel.

    Tanaka, E; Terada, M; Misawa, S; Wakasugi, C


    A high-performance liquid chromatographic method has been developed for the simultaneous analysis of twelve frequently used benzodiazepines (BZPs) (bromazepam, clonazepam, chlordiazepoxide, estazolam, etizolam, flutazoram, haloxazolam, lorazepam, nitrazepam, oxazolam, triazolam and diazepam, internal standard) by using commercially available 2 or 5 microns particle size reversed-phase columns and a microflow cell-equipped ultraviolet detector. The separation was achieved using a C18 reversed-phase column (condition 1: 100 x 4.6 mm I.D., particle size 2 microns, TSK gel Super-ODS: conditon 2: 100 x 4.6 mm I.D., particle size 5 microns, Hypersil ODS-C18). The mobile phase was composed of methanol-5 mM NaH2PO4 (pH 6) (45:55, v/v), and the flow-rate was 0.65 ml/min (condition 1 and 2). The absorbance of the eluent was monitored at 254 nm. Retention times under condition 1 were shorter than those of condition 2. When the twelve benzodiazepines were determined, sensitivity and limits of quantification were about four to ten times better under condition 1 than under condition 2. The rate of recovery and linearity in condition 1 were approximately the same as those in condition 2. These results show that a new ODS filler with a particle size of 2 microns was more sensitive, provided better separation and was more rapid than that with conventional ODS filler. PMID:8832439

  4. [Effects of psychotropic drugs on lateral hypothalamic self-stimulation behavior in rats: correlation between self-stimulation behavior inhibition and striatal dopaminergic blockade by neuroleptic drugs].

    Fukuda, T; Tsumagari, T


    The effects of neuroleptic drugs on self-stimulation behavior were investigated in rats with electrodes chronically implanted in the lateral hypothalamus. Except for sulpiride and carpipramine, the neuroleptic drugs chlorpromazine, thioridazine, perphenazine, haloperidol, floropipamide, pimozide, clocapramine and oxypertine all suppressed self-stimulation behavior dose-dependently. The anti-anxiety drugs chlordiazepoxide, diazepam, clotiazepam and etizolam facilitated this behavior. The antidepressant drugs imipramine and amitriptyline suppressed this behavior slightly at the dose of 40 mg/kg. The alpha-antagonist phenoxybenzamine also suppressed this behavior, but the slope of its dose-response curve was gentle compared with those of the neuroleptic drugs. The inhibition produced by the neuroleptic drugs is considered to be mediated primarily at the dopaminergic receptors. Turning behavior induced by methamphetamine in rats with unilateral 6-hydroxydopamine lesions of the caudate nucleus was used to assess the striatal dopaminergic blocking potency of the neuroleptic drugs. No correlation was found between the ED50 values for the turning behavior inhibition and the ED50 values for the self-stimulation behavior inhibition produced by these drugs, so the dopaminergic receptors in the striatum are apparently not involved in the mediation of self-stimulation behavior. PMID:6149172

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

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


    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

  6. Inpatient management of acute alcohol withdrawal syndrome.

    Perry, Elizabeth C


    Alcohol withdrawal is a common condition encountered in the hospital setting after abrupt discontinuation of alcohol in an alcohol-dependent individual. Patients may present with mild symptoms of tremulousness and agitation or more severe symptoms including withdrawal seizures and delirium tremens. Management revolves around early identification of at-risk individuals and symptom assessment using a validated tool such as the revised Clinical Institute Withdrawal Assessment for Alcohol score. Benzodiazepines remain the mainstay of treatment and can be administered using a front-loading, fixed-dose, or symptom-triggered approach. Long-acting benzodiazepines such as chlordiazepoxide or diazepam are commonly used and may provide a smoother withdrawal than shorter-acting benzodiazepines, but there are no data to support superiority of one benzodiazepine over another. Elderly patients or those with significant liver disease may have increased accumulation and decreased clearance of the long-acting benzodiazepines, and lorazepam or oxazepam may be preferred in these patients. Patients with symptoms refractory to high doses of benzodiazepines may require addition of a rescue medication such as phenobarbital, propofol or dexmedetomidine. Anticonvulsants (carbamazepine, valproate, gabapentin) may have a role in the management of mild to moderate withdrawal. Other medications such as β-antagonists or neuroleptics may offer additional benefit in select patients but should not be used a monotherapy. PMID:24781751

  7. A 'symptom-triggered' approach to alcohol withdrawal management.

    Murdoch, Jay; Marsden, Janet

    In acute hospital settings, alcohol withdrawal often causes significant management problems and complicates a wide variety of concurrent conditions, placing a huge burden on the NHS. A significant number of critical incidents around patients who were undergoing detoxification in a general hospital setting led to the need for a project to implement and evaluate an evidence-based approach to the management of alcohol detoxification-a project that included a pre-intervention case note audit, the implementation of an evidence-based symptom-triggered detoxification protocol, and a post-intervention case note audit. This change in practice resulted in an average reduction of almost 60% in length of hospital stay and a 66% reduction in the amount of chlordiazepoxide used in detoxification, as well as highlighting that 10% of the sample group did not display any signs of withdrawal and did not require any medication. Even with these reductions, no patient post-intervention developed any severe signs of withdrawal phenomena, such as seizures or delirium tremens. The savings to the trust (The Pennine Acute Hospital Trust) are obvious,but the development of a consistent, quality service will lead to fewer long-term negative effects for patients that can be caused by detoxification. This work is a project evaluation of a locally implemented strategy, which, it was hypothesised,would improve care by providing an individualised treatment plan for the management of alcohol withdrawal symptoms. PMID:24809146

  8. Neuroleptic drugs revert the contextual fear conditioning deficit presented by spontaneously hypertensive rats: a potential animal model of emotional context processing in schizophrenia?

    Calzavara, Mariana Bendlin; Medrano, Wladimir Agostini; Levin, Raquel; Kameda, Sonia Regina; Andersen, Monica Levy; Tufik, Sergio; Silva, Regina Helena; Frussa-Filho, Roberto; Abílio, Vanessa Costhek


    Schizophrenia, bipolar disorder, and attention deficit/hyperactivity disorder (ADHD) present abnormalities in emotion processing. A previous study showed that the spontaneously hypertensive rats (SHR), a putative animal model of ADHD, present reduced contextual fear conditioning (CFC). The aim of the present study was to characterize the deficit in CFC presented by SHR. Adult male normotensive Wistar rats and SHR were submitted to the CFC task. Sensitivity of the animals to the shock and the CFC performance after repeated exposure to the task were investigated. Pharmacological characterization consisted in the evaluation of the effects of the following drugs administered previously to the acquisition of the CFC: pentylenetetrazole (anxiogenic) and chlordiazepoxide (anxiolytic); methylphenidate and amphetamine (used for ADHD); lamotrigine, carbamazepine, and valproic acid (mood stabilizers); haloperidol, ziprasidone, risperidone, amisulpride, and clozapine (neuroleptic drugs); metoclopramide and SCH 23390 (dopamine antagonists without antipsychotic properties); and ketamine (a psychotomimmetic). The effects of paradoxical sleep deprivation (that worsens psychotic symptoms) and the performance in a latent inhibition protocol (an animal model of schizophrenia) were also verified. No differences in the sensitivity to the shock were observed. The repeated exposure to the CFC task did not modify the deficit in CFC presented by SHR. Considering pharmacological treatments, only the neuroleptic drugs reversed this deficit. This deficit was potentiated by proschizophrenia manipulations. Finally, a deficit in latent inhibition was also presented by SHR. These findings suggest that the deficit in CFC presented by SHR could be a useful animal model to study abnormalities in emotional context processing related to schizophrenia. PMID:18281713

  9. Alcohol detoxification in Ysbyty Gwynedd: Two small sips or one big gulp? Two-step screening more reliable for identification of alcohol dependency syndrome at risk of delirium tremens for routine care.

    Salman, Muhammad; Subbe, Christian


    Compliance with pathways for hospitalised patients with alcohol dependency syndrome is often poor. A pathway for recognition and treatment of alcohol dependency was redesigned as part of a 12 month service improvement project in the acute medical unit using plan, do, study, act (PDSA) cycles. A needs assessment was undertaken: Audit data from 2013 showed over-prescription of chlordiazepoxide for detoxification treatment (DT) leading to prolonged hospital admissions with an average length of stay of 5.5 days in 2012/2013. Acceptability of screening tools was tested: Common screening tools (CEWA, AUDIT) were rejected by junior doctors due to the high number of questions as too cumbersome for routine practice. Compliance with usage in random samples over a three month period was persistently (n=10%. Testing of an abbreviated AUDIT questionnaire with only two questions and a specified threshold showed a AUROC of 1 (ptool was implemented in several PDSAs cycles. After the final cycle a random sample of 100 patients was reviewed for pathway compliance over a three months period. Eighty-six patients were screened with the two-question tool of these 18 were identified as possible risk. Of these 16 patients had the full AUDIT questionnaire, only eight with elevated values were started on DT. Overall compliance with the pathway increased to 84%. PMID:26734413

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

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


    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

  11. Treatment of the irritable bowel syndrome.

    Friedman, G


    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

  12. Anxiolytic-like actions of the selective 5-HT4 receptor antagonists SB 204070A and SB 207266A in rats.

    Kennett, G A; Bright, F; Trail, B; Blackburn, T P; Sanger, G J


    The highly selective 5-HT4 receptor antagonists, SB 204070A (0.001-0.1 mg/kg s.c., 30 min pretest) and SB 207266A (0.01, 1 and 10 mg/kg p.o., 1 hr pre-test), increased time spent in social interaction without affecting locomotor activity, in a rat 15 min social interaction test under high light, unfamiliar conditions. At 1 and 10 mg/kg s.c., SB 204070A was no longer active. These results are consistent with the profile expected of anxiolytic treatments in this procedure. In a rat 5 min elevated x-maze test, SB 204070A (0.01 and 1 mg/kg s.c., 30 min pre-test) significantly increased the percentage of time spent on the open arms. SB 204070A (0.01 mg/kg s.c.) and SB 207266A (1 mg/kg p.o., 1 hr pre-test) also increased percentage entries to the open arms. Neither compound affected locomotion at any dose tested in the procedure. The effects of both compounds in this procedure are also consistent with anxiolysis. Neither SB 204070A (0.1 or 1 mg/kg s.c., 30 min pre-test) nor SB 207266A (0.1 or 1 mg/kg p.o., 1 hr pre-test) affected either unpunished or punished responding, in a rat Geller-Seifter conflict model of anxiety. The maximal efficacy of both SB 204070A and SB 207266A in the rat social interaction test was similar to that of the benzodiazepine anxiolytic chlordiazepoxide (5 mg/kg s.c. or p.o.) used as a positive control, but was considerably less in the elevated x-maze procedure. The results suggest that 5-HT4 receptor antagonists may have modest anxiolytic-like actions in rats. PMID:9225297

  13. Effects of the 5-HT2B receptor agonist, BW 723C86, on three rat models of anxiety.

    Kennett, G A; Bright, F; Trail, B; Baxter, G S; Blackburn, T P


    1. BW 723C86 (3 and 10 mg kg-1, s.c. 30 min pretest), a 5-HT2B receptor agonist, increased total interaction, but not locomotion in a rat social interaction test, a profile consistent with anxiolysis. 2. The effect of BW 723C86 in the social interaction test is likely to be 5-HT2B receptor-mediated as it was prevented by pretreatment with the 5-HT2C/2B receptor antagonist, SB 200646A, (1 and 2 mg kg-1, p.o., 1 h pretest) which did not affect basal levels of social interaction at the doses used. 3. An anxiolytic-like action was also observed in the rat Geller-Seifter conflict test, where BW 723C86 (0.5-50 mg kg-1, s.c. 30 min pretest) modestly, but significantly increased punished, but not unpublished responding. 4. In a rat 5 min elevated x-maze test, BW 723C86 (1-10 mg kg-1, s.c.) had no significant effect. 5. The maximal anxiolytic-like effect of BW 723C86 approached that of the benzodiazepine anxiolytic, chloradiazepoxide (5 mg kg-1, s.c. 30 min pretest) in the social interaction test, but was markedly less in the Geller-Siefter test. The effect of BW 723C86 was also clearly less than chlordiazepoxide in the elevated x-maze procedure where it had no significant effect. 6. In conclusion, BW 723C86 exerted an appreciable anxiolytic-like profile in a rat social interaction test, but had a weaker effect in the Geller-Siefter and was ineffective in the elevated x-maze test used. These effects are likely to be 5-HT2B receptor-mediated. PMID:8730737

  14. Dopamine D4 receptor and anxiety: behavioural profiles of clozapine, L-745,870 and L-741,742 in the mouse plus-maze.

    Cao, B J; Rodgers, R J


    The dopamine D4 receptor has been implicated in the therapeutic effects of the atypical antipsychotic, clozapine. As it has been proposed that anxiolytic-like activity may contribute to the efficacy of this agent in ameliorating the negative symptoms of schizophrenia, the current study employed ethological methods to fully characterize the acute behavioural profiles of clozapine and two more selective dopamine D4 receptor antagonists, L-745,870 (3-[{4-(4-chlorophenyl)piperazin-1-yl)]methyl}-1 H-pyrrolo[2,3b]pyridine) and L-741,742 (5-(4-chlorophenyl)-4-methyl-3-(1-(2-phenylethyl)piperidin-4-yl)is oxazole), in the mouse elevated plus-maze test. Results showed that while clozapine (0.3-6.0 mg/kg) dose-dependently inhibited all active behaviours (arm entries, exploration, rearing) and increased grooming and immobility, it failed to alter the major anxiety indices (percent open entries and open time). In contrast, L-745,870 (0.02-1.5 mg/kg) and L-741,742 (0.04-5.0 mg/kg) did not produce any significant behavioural changes under present test conditions. These data, which contrast markedly with the robust anxiolytic profile of the reference compound, chlordiazepoxide (10.0 mg/kg), provide little support for the suggestion that clozapine possesses anxiolytic-like properties and further indicate that selective dopamine D4 receptor antagonists are ineffective in the modulation of anxiety-related behaviours in the plus-maze. PMID:9369363

  15. Identification of a Glycogen Synthase Kinase-3[beta] Inhibitor that Attenuates Hyperactivity in CLOCK Mutant Mice

    Kozikowski, Alan P.; Gunosewoyo, Hendra; Guo, Songpo; Gaisina, Irina N.; Walter, Richard L.; Ketcherside, Ariel; McClung, Colleen A.; Mesecar, Andrew D.; Caldarone, Barbara (Psychogenics); (Purdue); (UIC); (UTSMC)


    Bipolar disorder is characterized by a cycle of mania and depression, which affects approximately 5 million people in the United States. Current treatment regimes include the so-called 'mood-stabilizing drugs', such as lithium and valproate that are relatively dated drugs with various known side effects. Glycogen synthase kinase-3{beta} (GSK-3{beta}) plays a central role in regulating circadian rhythms, and lithium is known to be a direct inhibitor of GSK-3{beta}. We designed a series of second generation benzofuran-3-yl-(indol-3-yl)maleimides containing a piperidine ring that possess IC{sub 50} values in the range of 4 to 680 nM against human GSK-3{beta}. One of these compounds exhibits reasonable kinase selectivity and promising preliminary absorption, distribution, metabolism, and excretion (ADME) data. The administration of this compound at doses of 10 to 25 mg kg{sup -1} resulted in the attenuation of hyperactivity in amphetamine/chlordiazepoxide-induced manic-like mice together with enhancement of prepulse inhibition, similar to the effects found for valproate (400 mg kg{sup -1}) and the antipsychotic haloperidol (1 mg kg{sup -1}). We also tested this compound in mice carrying a mutation in the central transcriptional activator of molecular rhythms, the CLOCK gene, and found that the same compound attenuates locomotor hyperactivity in response to novelty. This study further demonstrates the use of inhibitors of GSK-3{beta} in the treatment of manic episodes of bipolar/mood disorders, thus further validating GSK-3{beta} as a relevant therapeutic target in the identification of new therapies for bipolar patients.

  16. Carisoprodol-mediated modulation of GABAA receptors: in vitro and in vivo studies.

    Gonzalez, Lorie A; Gatch, Michael B; Taylor, Cynthia M; Bell-Horner, Cathy L; Forster, Michael J; Dillon, Glenn H


    Carisoprodol is a frequently prescribed muscle relaxant. In recent years, this drug has been increasingly abused. The effects of carisoprodol have been attributed to its metabolite, meprobamate, a controlled substance that produces sedation via GABA(A) receptors (GABA(A)Rs). Given the structural similarities between carisoprodol and meprobamate, we used electrophysiological and behavioral approaches to investigate whether carisoprodol directly affects GABA(A)R function. In whole-cell patch-clamp studies, carisoprodol allosterically modulated and directly activated human alpha1beta2gamma2 GABA(A)R function in a barbiturate-like manner. At millimolar concentrations, inhibitory effects were apparent. Similar allosteric effects were not observed for homomeric rho1 GABA or glycine alpha1 receptors. In the absence of GABA, carisoprodol produced picrotoxin-sensitive, inward currents that were significantly larger than those produced by meprobamate, suggesting carisoprodol may directly produce GABAergic effects in vivo. When administered to mice via intraperitoneal or oral routes, carisoprodol elicited locomotor depression within 8 to 12 min after injection. Intraperitoneal administration of meprobamate depressed locomotor activity in the same time frame. In drug discrimination studies with carisoprodol-trained rats, the GABAergic ligands pentobarbital, chlordiazepoxide, and meprobamate each substituted for carisoprodol in a dose-dependent manner. In accordance with findings in vitro, the discriminative stimulus effects of carisoprodol were antagonized by a barbiturate antagonist, bemegride, but not by the benzodiazepine site antagonist, flumazenil. The results of our studies in vivo and in vitro collectively suggest the barbiturate-like effects of carisoprodol may not be due solely to its metabolite, meprobamate. Furthermore, the functional traits we have identified probably contribute to the abuse potential of carisoprodol. PMID:19244096

  17. Evidências advindas do consumo de medicamentos moduladores do apetite no Brasil: um estudo farmacoeconométrico Evidence for the use of appetite suppressant drugs in Brazil: a pharmacoeconometric study

    Daniel Marques Mota


    cross-sectional data to analyze the relationship between the use of appetite suppressants (mg/per capita and the independent variables selected (gender, race/color, age, schooling, income, health insurance coverage, and use of fluoxetine and chlordiazepoxide using multiple linear regression analysis. This study used these variables in level of aggregation by states for 2009. The analyses were performed using the Gretl software. RESULTS: We highlight that São Paulo showed the highest use of appetite suppressants with 97.3 mg/per capita, followed by Goiás with 94.8 mg/per capita. The lowest use of appetite suppressants was seen in Ceará (3.8 mg/per capita. The biggest fluoxetine users were in Rio Grande do Sul, with 58.0 mg/per capita, and in Goiás, with 51.5 mg/per capita. Ceará showed the lowest fluoxetine use (2.3 mg/per capita. For chlordiazepoxide, the highest values were seen in Minas Gerais (7.5 mg/per capita and in Rio de Janeiro (4.8 mg/per capita, while Amazonas (0.08 mg/per capita showed the lowest use. Based on regression analysis, we can highlight: 1 the use of appetite suppressants is related to income, education, and fluoxetine use; and 2 race/color, gender, age, health insurance coverage, and use of chlordiazepoxide showed no relation to the use of appetite suppressants. CONCLUSION: These evidences may contribute to the improvement of regulatory actions, sanitary surveillance, and ethical conduct, particularly with regard to the concomitant use of appetite suppressants and fluoxetine, which is prohibited by the Federal Council of Medicine (Conselho Federal de Medicina and also by Anvisa (Agência Nacional de Vigilância Sanitária - National Health Surveillance Agency.

  18. Alcohol abuse and related disorders treatment of alcohol dependence

    Yu. P. Sivolap


    Full Text Available Alcohol abuse and alcoholism are the leading causes of worse health and increased mortality rates. Excessive alcohol consumption is the third leading cause of the global burden of diseases and a leading factor for lower lifespan and higher mortality. Alcohol abuse decreases working capacity and efficiency and requires the increased cost of the treatment of alcohol-induced disorders, which entails serious economic losses. The unfavorable medical and social consequences of excessive alcohol use determine the importance of effective treatment for alcoholism. The goals of rational pharmacotherapy of alcohol dependence are to enhance GABA neurotransmission, to suppress glutamate neurotransmission, to act on serotonin neurotransmission, to correct water-electrolyte balance, and to compensate for thiamine deficiency. Alcoholism treatment consists of two steps: 1 the prevention and treatment of alcohol withdrawal syndrome and its complications (withdrawal convulsions and delirium alcoholicum; 2 antirecurrent (maintenance therapy. Benzodiazepines are the drugs of choice in alleviating alcohol withdrawal and preventing its convulsive attacks and delirium alcoholicum. Diazepam and chlordiazepoxide are most commonly used for this purpose; the safer drugs oxazepam and lorazepam are given to the elderly and patients with severe liver lesions. Anticonvulsants having normothymic properties, such as carbamazepine, valproic acid, topiramate, and lamotrigine, are a definite alternative to benzodiazepines. The traditional Russian clinical practice (clearance detoxification has not a scientific base or significant impact on alcohol withdrawal-related states in addicts. Relapse prevention and maintenance therapy for alcohol dependence are performed using disulfiram, acamprosate, and naltrexone; since 2013 the European Union member countries have been using, besides these agents, nalmefene that is being registered in Russia. Memantine and a number of other

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

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


    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. Collaborative study on fifteen compounds in the rat-liver Comet assay integrated into 2- and 4-week repeat-dose studies.

    Rothfuss, Andreas; O'Donovan, Mike; De Boeck, Marlies; Brault, Dominique; Czich, Andreas; Custer, Laura; Hamada, Shuichi; Plappert-Helbig, Ulla; Hayashi, Makoto; Howe, Jonathan; Kraynak, Andrew R; van der Leede, Bas-jan; Nakajima, Madoka; Priestley, Catherine; Thybaud, Veronique; Saigo, Kazuhiko; Sawant, Satin; Shi, Jing; Storer, Richard; Struwe, Melanie; Vock, Esther; Galloway, Sheila


    A collaborative trial was conducted to evaluate the possibility of integrating the rat-liver Comet assay into repeat-dose toxicity studies. Fourteen laboratories from Europe, Japan and the USA tested fifteen chemicals. Two chemicals had been previously shown to induce micronuclei in an acute protocol, but were found negative in a 4-week Micronucleus (MN) Assay (benzo[a]pyrene and 1,2-dimethylhydrazine; Hamada et al., 2001); four genotoxic rat-liver carcinogens that were negative in the MN assay in bone marrow or blood (2,6-dinitrotoluene, dimethylnitrosamine, 1,2-dibromomethane, and 2-amino-3-methylimidazo[4,5-f]quinoline); three compounds used in the ongoing JaCVAM (Japanese Center for the Validation of Alternative Methods) validation study of the acute liver Comet assay (2,4-diaminotoluene, 2,6-diaminotoluene and acrylamide); three pharmaceutical-like compounds (chlordiazepoxide, pyrimethamine and gemifloxacin), and three non-genotoxic rodent liver carcinogens (methapyrilene, clofibrate and phenobarbital). Male rats received oral administrations of the test compounds, daily for two or four weeks. The top dose was meant to be the highest dose producing clinical signs or histopathological effects without causing mortality, i.e. the 28-day maximum tolerated dose. The liver Comet assay was performed according to published recommendations and following the protocol for the ongoing JaCVAM validation trial. Laboratories provided liver Comet assay data obtained at the end of the long-term (2- or 4-week) studies together with an evaluation of liver histology. Most of the test compounds were also investigated in the liver Comet assay after short-term (1-3 daily) administration to compare the sensitivity of the two study designs. MN analyses were conducted in bone marrow or peripheral blood for most of the compounds to determine whether the liver Comet assay could complement the MN assay for the detection of genotoxins after long-term treatment. Most of the liver genotoxins