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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. 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…

  3. 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...

  4. 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.

  5. 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

  6. 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

  7. 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...

  8. 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. ...

  9. Buspirone Versus Methylphenidate in the Treatment of Children with Attention- Deficit/ Hyperactivity Disorder: Randomized Double-Blind Study

    OpenAIRE

    Shahin Akhondzadeh; Reza Hajiaghaee; Ali Galeiha; Poopak Hafezi; Mohammad-Reza Mohammadi

    2012-01-01

    A recent randomized clinical trial showed buspirone efficacy in the treatment of attention-deficit/hyperactivity disorder (ADHD) in children. However, results from a recent multi-site controlled clinical trial of transdermal buspirone failed to separate it from placebo in a large sample of children with ADHD. Therefore, due to these inconsistent findings, this study was designed to assess the efficacy of buspirone in the treatment of children with ADHD compared to methylphenidate in a double ...

  10. The Effect of Chronic Administration of Buspirone on 6-Hydroxydopamine-Induced Catalepsy in Rats

    Directory of Open Access Journals (Sweden)

    Hamdolah Sharifi

    2012-06-01

    Full Text Available Purpose: Several evidences show that serotonergic neurons play a role in the regulation of movements executed by the basal ganglia. Recently we have reported that single dose of buspirone improved 6-hydroxydopamine (6-OHDA and haloperidol-induced catalepsy. This study is aimed to investigate effect of chronic intraperitoneal (i.p. administration of buspirone on 6-OHDA-induced catalepsy in male Wistar rats. Methods: Catalepsy was induced by unilateral infusion of 6-OHDA (8 μg/2 μl/rat into the central region of the SNc and was assayed by the bar-test method 5, 60, 120 and 180 min after drugs administration in 10th day. The effect of buspirone (0.5, 1 and 2 mg/kg, i.p. for 10 days was assessed in 6-OHDA-lesioned rats. Results: The results showed that chronic injection of buspirone (0.5, 1 and 2 mg/kg, i.p. for 10 days decreased catalepsy when compared with the control group. The best anticataleptic effect was observed at the dose of 1 mg/kg. The catalepsy-improving effect of buspirone was reversed by 1-(2-methoxyphenyl- 4-[4-(2-phthalimido butyl]piperazine hydrobromide (NAN-190, 0.5 mg/kg, i.p.,as a 5-HT1A receptor antagonist. Conclusion: Our study indicates that chronic administration of buspirone improves catalepsy in a 6-OHDA-induced animal model of parkinson's disease (PD. We also suggest that buspirone may be used as an adjuvant therapy to increase effectiveness of antiparkinsonian drugs. In order to prove this hypothesis, further clinical studies should be done.

  11. 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...

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

    Directory of Open Access Journals (Sweden)

    M Sarangapani

    2011-10-01

    Full Text Available 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 seven days was compared with an oral solution of 10 mg kg-1 of buspirone in distilled water. Animals were allowed free access to food and water, until night prior to dosing and were fasted for 10 hrs. In the first phase oral solution (10 mg kg-1 was administered through feeding tube followed by rinsing with 10 ml of water. In the second phase, the group was pretreated with pomegranate juice for 7 days and study was conducted after 15 days of washout period. Results and conclusion: The results showed that there was a significant (p<0.05 difference in the bioavailability of buspirone after pre-treatment with pomegranate juice.This increase in bioavailability might be due to inhibition of CYP3A4. Further studies are required to prove this mechanism in humans.

  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. Attenuation of methylphenidate-induced sensitization by co-administration of buspirone.

    Science.gov (United States)

    Alam, Nausheen; Najam, Rahila; Naeem, Sadaf

    2016-03-01

    Methylphenidate, which inhibit dopamine transporter is effective in the treatment of ADHD (attention deficit hyperactivity disorder), but long term use of this drug is often associated with addiction and dependence. Locomotor sensitization development to psychostimulants like methylphenidate is an important contributor to drug abuse induced by psychostimulants. Different studies have shown that long term administration of drugs of abuse increases the effectiveness of 5-hydroxytryptamine (5-HT)-1A somatodendritic receptors. Repeated buspirone administration reduces the effectiveness of 5-HT1A somatodendritic receptors. This study was designed to determine that buspirone co-administration may reduce methylphenidate-induced sensitization. The motor activity was compared by using familiar and novel environments after long-term administration of methylphenidate, buspirone and their co-administration. Long term oral administration of methylphenidate at a dose of 2.0mg/kg/day enhanced motor activity in home cage i.e. activity of familiar environment monitored at alternate day. Locomotor enhancing effects of methylphenidate were augmented on 13th day of drug administration suggesting sensitization induced by the drug. The sensitization effects were significant in home cage monitored on alternate day and also in an open field monitored weekly. Buspirone co-administration at a dose of 10mg/kg/day prevented methylphenidate-induced sensitization. It is suggested that the sensitization development to methylphenidate may oppose by buspirone co-administration due to the reduction in the sensitivity of 5-HT1A somatodendritic receptors. These findings may help extend future therapeutics in ADHD. PMID:27087081

  15. Behavioral studies with anxiolytic drugs. IV. Serotonergic involvement in the effects of buspirone on punished behavior of pigeons

    Energy Technology Data Exchange (ETDEWEB)

    Witkin, J.M.; Mansbach, R.S.; Barrett, J.E.; Bolger, G.T.; Skolnick, P.; Weissman, B.

    1987-12-01

    Interactions of the nonbenzodiazepine anxiolytic, buspirone, with serotonin (5-HT) were studied using behavioral and neurochemical procedures. Punished responding was studied in pigeons as this behavior is a generally acknowledged preclinical predictor of anxiolytic activity and because buspirone increases punished responding of pigeons with greater potency and efficacy than in other species. Keypeck responses were maintained under either fixed-interval or fixed-ratio schedules of food presentation; every 30th response produced a brief electric shock and suppressed responding (punishment). Buspirone (0.1-5.6 mg/kg i.m.) produced dose-related increases in punished responding which reached a maximum at 1 mg/kg. A serotonin agonist, MK-212 (0.01 mg/kg), antagonized whereas the 5-HT antagonist, cyproheptadine (0.01 mg/kg), potentiated the effects of buspirone without having behavioral effects of their own. The characteristics of (/sup 3/H)-5-HT binding in pigeon brain membranes were similar to results reported in mammalian brain. Neither buspirone, MJ-13805 (gepirone, a related analog), nor MJ-13653 (a buspirone metabolite), significantly affected (/sup 3/H)-5-HT binding and none of the compounds appreciably inhibited uptake of (/sup 3/H)-5-HT into pigeon cerebral synaptosomes. Hill coefficients significantly less than unity for all drugs except 5-HT suggested multiple serotonergic binding sites for buspirone and analogs. Buspirone and MJ-13805 (1 nM) inhibited (/sup 3/H)ketanserin binding (a measure of 5-HT2 binding sites) in pigeon cerebrum with Ki values above 10(-6) M. The number of (/sup 3/H)ketanserin binding sites was estimated to be 109 fmol/mg of protein in pigeon cerebrum compared to 400 fmol/mg of protein in rat cerebrum.

  16. Behavioral studies with anxiolytic drugs. IV. Serotonergic involvement in the effects of buspirone on punished behavior of pigeons

    International Nuclear Information System (INIS)

    Interactions of the nonbenzodiazepine anxiolytic, buspirone, with serotonin (5-HT) were studied using behavioral and neurochemical procedures. Punished responding was studied in pigeons as this behavior is a generally acknowledged preclinical predictor of anxiolytic activity and because buspirone increases punished responding of pigeons with greater potency and efficacy than in other species. Keypeck responses were maintained under either fixed-interval or fixed-ratio schedules of food presentation; every 30th response produced a brief electric shock and suppressed responding (punishment). Buspirone (0.1-5.6 mg/kg i.m.) produced dose-related increases in punished responding which reached a maximum at 1 mg/kg. A serotonin agonist, MK-212 (0.01 mg/kg), antagonized whereas the 5-HT antagonist, cyproheptadine (0.01 mg/kg), potentiated the effects of buspirone without having behavioral effects of their own. The characteristics of [3H]-5-HT binding in pigeon brain membranes were similar to results reported in mammalian brain. Neither buspirone, MJ-13805 (gepirone, a related analog), nor MJ-13653 (a buspirone metabolite), significantly affected [3H]-5-HT binding and none of the compounds appreciably inhibited uptake of [3H]-5-HT into pigeon cerebral synaptosomes. Hill coefficients significantly less than unity for all drugs except 5-HT suggested multiple serotonergic binding sites for buspirone and analogs. Buspirone and MJ-13805 (1 nM) inhibited [3H]ketanserin binding (a measure of 5-HT2 binding sites) in pigeon cerebrum with Ki values above 10(-6) M. The number of [3H]ketanserin binding sites was estimated to be 109 fmol/mg of protein in pigeon cerebrum compared to 400 fmol/mg of protein in rat cerebrum

  17. Buspirone improves haloperidol-induced Parkinson disease in mice through 5-HT1A recaptors

    OpenAIRE

    Mohajjel Nayebi A, A; H Sheidaei

    2010-01-01

    Background and the purpose of the study The available literatures show that 5-HT1A receptors are widely distributed throughout the basal ganglia, and their activation facilitate dopamine release. Neuroleptic drugs such as haloperidol induce Parkinson-like syndrome through blocking brain D2 receptors. This study aimed to investigate effect of buspirone, a partial agonist of 5HT1A receptor, on motor dysfunctions induced by haloperidol and involvement of 5HT1A receptors in this regard. Methods S...

  18. Buspirone improves haloperidol-induced Parkinson disease in mice through 5-HT1A receptors

    OpenAIRE

    A. Mohajjel Nayebi; H Sheidaei

    2010-01-01

    "nBackground and the purpose of the study: The available literatures show that 5-HT1A receptors are widely distributed throughout the basal ganglia, and their activation facilitate dopamine release. Neuroleptic drugs such as haloperidol induce Parkinson-like syndrome through blocking brain D2 receptors. This study aimed to investigate effect of buspirone, a partial agonist of 5HT1A receptor, on motor dysfunctions induced by haloperidol and involvement of 5HT1A receptors in this regard. &...

  19. Flow injection analysis with tubular membrane ion-selective electrode and coated wires for buspirone hydrochloride.

    Science.gov (United States)

    Abdel-Ghani, Nour; Issa, Yousry; Shoukry, Adel; Ahmed, Howayda

    2007-01-01

    New Plastic membrane ion-selective electrode for buspirone hydrochloride based on buspironium tetraphenylborate was prepared. The electrode exhibited mean slope of calibration graph of 58.4 mV per decade of BusCl concentration at 25 degrees C. The electrode can be used within the concentration range 6.3 x 10(-5) - 10(-2) M BusCl at a pH range of 2.5-7.0. The standard electrode potentials were determined at different temperatures and used to calculate the isothermal temperature coefficient of the electrode, amounting to 0.00056 V degrees C(-1). The electrode showed a very good selectivity for BusCl with respect to a number of inorganic cations, sugars and amino acids. The electrode was applied to the potentiometric determination of the buspirone ion and its pharmaceutical preparation under batch and flow injection conditions. Also, buspirone was determined by conductimetric titrations. Graphite rod, copper and silver coated wire electrodes were prepared and characterized as sensors for the drug under investigation. PMID:17822267

  20. Buspirone versus methylphenidate in the treatment of children with attention- deficit/ hyperactivity disorder: randomized double-blind study.

    Science.gov (United States)

    Mohammadi, Mohammad-Reza; Hafezi, Poopak; Galeiha, Ali; Hajiaghaee, Reza; Akhondzadeh, Shahin

    2012-01-01

    A recent randomized clinical trial showed buspirone efficacy in the treatment of attention-deficit/hyperactivity disorder (ADHD) in children. However, results from a recent multi-site controlled clinical trial of transdermal buspirone failed to separate it from placebo in a large sample of children with ADHD. Therefore, due to these inconsistent findings, this study was designed to assess the efficacy of buspirone in the treatment of children with ADHD compared to methylphenidate in a double blind randomized clinical trial. Forty outpatients with a DSM-IV-TR diagnosis of ADHD were study population of this trial. Subjects were recruited from an outpatient child and adolescent clinic for a 6 week double blind, randomized clinical trial. All study subjects were randomly assigned to receive treatment using tablet of buspirone at a dose of 20-30 mg/day depending on weight (20 mg/day for 30kg) (group 1) or methylphenidate at a dose of 20-30 mg/day depending on weight (20 mg/day for 30kg (group 2) for a 6 week double blind, randomized clinical trial. The principal measure of outcome was the Teacher and Parent ADHD Rating Scale IV. Patients were assessed at baseline and at 21 and 42 days after the medication started. Significant differences were observed between the two groups on the Parent and Teacher Rating Scale scores. The changes at the endpoint compared to baseline were: -8.95±8.73 (mean±SD) and -15.60±7.81 (mean±SD) for buspirone and methyphenidate, for Parent ADHD Rating Scale. The changes at the endpoint compared to baseline were: -9.80 ±7.06 (mean±SD) and -22.40±9.90 (mean±SD) for buspirone and methyphenidate, respectively for Teacher ADHD Rating Scale. The difference between the buspirone and methylphenidate groups in the frequency of side effects was not significant except for decreased appetite, headache and insomnia that were observed more frequently in the methylphenidate group. The results of this study suggest that administration of buspirone was

  1. 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...... intention to treat sample was used. Results: Within the pharmacopsychometric triangle, bupropion-SR (sustained release) was superior to buspirone when augmented to the current citalopram treatment. Thus, in the domain of pure antidepressive effect, bupropion-SR was superior (P = 0.05) on the HAM-D(6) , IDS...... depressed outpatients not responding to citalopram....

  2. Buspirone Versus Methylphenidate in the Treatment of Children with Attention- Deficit/ Hyperactivity Disorder: Randomized Double-Blind Study

    Directory of Open Access Journals (Sweden)

    Shahin Akhondzadeh

    2012-11-01

    Full Text Available A recent randomized clinical trial showed buspirone efficacy in the treatment of attention-deficit/hyperactivity disorder (ADHD in children. However, results from a recent multi-site controlled clinical trial of transdermal buspirone failed to separate it from placebo in a large sample of children with ADHD. Therefore, due to these inconsistent findings, this study was designed to assess the efficacy of buspirone in the treatment of children with ADHD compared to methylphenidate in a double blind randomized clinical trial. Forty outpatients with a DSM-IV-TR diagnosis of ADHD were study population of this trial. Subjects were recruited from an outpatient child and adolescent clinic for a 6 week double blind, randomized clinical trial. All study subjects were randomly assigned to receive treatment using tablet of buspirone at a dose of 20-30 mg/day depending on weight (20 mg/day for 30kg (group 1 or methylphenidate at a dose of 20-30 mg/day depending on weight (20 mg/day for 30kg (group 2 for a 6 week double blind, randomized clinical trial. The principal measure of outcome was the Teacher and Parent ADHD Rating Scale IV. Patients were assessed at baseline and at 21 and 42 days after the medication started. Significant differences were observed between the two groups on the Parent and Teacher Rating Scale scores. The changes at the endpoint compared to baseline were: -8.95±8.73 (mean±SD and -15.60±7.81 (mean±SD for buspirone and methyphenidate, for Parent ADHD Rating Scale. The changes at the endpoint compared to baseline were: -9.80 ±7.06 (mean±SD and -22.40±9.90 (mean±SD for buspirone and methyphenidate, respectively for Teacher ADHD Rating Scale. The difference between the buspirone and methylphenidate groups in the frequency of side effects was not significant except for decreased appetite, headache and insomnia that were observed more frequently in the methylphenidate group. The results of this study suggest that administration of

  3. 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)

  4. 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

  5. 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...

  6. 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...

  7. 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

  8. 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

  9. 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

  10. 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.

  11. Treatment of anxiety disorders and comorbid alcohol abuse with buspirone in a patient with antidepressant-induced platelet dysfunction: a case report.

    Science.gov (United States)

    Mazhar, Mir; Hassan, Tariq; Munshi, Tariq

    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 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. PMID:24416612

  12. 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.

  13. 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...

  14. 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

  15. 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.

  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. 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...

  20. 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.

  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. 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.

  3. 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

  4. EuroHYP-1

    DEFF Research Database (Denmark)

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

    2014-01-01

    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...

  5. 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…

  6. 5-HT1A receptors mediate the effect of the bulbospinal serotonin system on spinal dorsal horn nociceptive neurons.

    Science.gov (United States)

    Zemlan, F P; Murphy, A Z; Behbehani, M M

    1994-01-01

    The present study examined whether the effect of stimulation of the nucleus raphe magnus (NRM) is mediated by spinal cord dorsal horn serotonin1A (5-HT1A) receptors in the rat. This hypothesis predicts that nociceptive dorsal horn units inhibited by NRM stimulation or iontophoretic 5-HT application would also be inhibited by iontophoresis of the selective 5-HT1A agonists 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and buspirone. A total of 78 dorsal horn wide-dynamic-range neurons were recorded. Overall, 62% of the cells tested (48/78) were responsive to electrical stimulation of the NRM with the predominant response being inhibitory (38/48; 79%). Fifty-eight cells were tested for their response to both NRM stimulation and 8-OH-DPAT iontophoresis: 20/58 cells were inhibited by NRM stimulation and 50% of the cells inhibited by NRM stimulation were also inhibited by 8-OH-DPAT. Fifty-two cells were tested for their response to both NRM stimulation and buspirone iontophoresis: 14/52 cells were inhibited by NRM stimulation with 9/14 similarly inhibited by buspirone. To examine whether exogenously applied serotonin produced an effect through 5-HT1A receptors, the effect of both 5-HT and 8-OH-DPAT iontophoresis was tested on 57 dorsal horn neurons. The majority of cells (25/57) were inhibited by 5-HT application; 15/25 were similarly inhibited by 8-OH-DPAT. The response of 48 dorsal horn cells to 5-HT and buspirone iontophoresis was compared. Forty-four percent (21/48) of the cells were inhibited by 5-HT; 16/21 were also inhibited by buspirone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8309982

  7. 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...

  8. Advances in the Management of Treatment-Resistant Depression

    OpenAIRE

    Holtzheimer, Paul E.

    2010-01-01

    Treatment-resistant depression (TRD) is a prevalent, disabling, and costly condition affecting 1%–4% of the U.S. population. Current approaches to managing TRD include medication augmentation (with lithium, thyroid hormone, buspirone, atypical antipsychotics, or various antidepressant medications), psychotherapy, and ECT. Advances in understanding the neurobiology of mood regulation and depression have led to a number of new potential approaches to managing TRD, including medications with nov...

  9. Effect of drugs modulating serotonergic system on the analgesic action of paracetamol in mice

    Science.gov (United States)

    Karandikar, Yogita S.; Belsare, Peeyush; Panditrao, Aditi

    2016-01-01

    Objective: The underlying mechanisms for the analgesic action of paracetamol (PCT) are still under considerable debate. It has been recently proposed that PCT may act by modulating the Serotonin system. This study was conducted to verify the influence of Serotonin modulating drugs (buspirone, ondansetron, and fluoxetine) on the analgesic effect of PCT. Materials and Methods: Thirty adult albino mice were assigned to five groups: Normal saline, PCT, fluoxetine selective serotonin reuptake inhibitor (SSRI) + PCT, buspirone (5-HT1A Agonist) + PCT, and ondansetron (5HT3 antagonist) + PCT. Hot-plate and formalin test were used to determine pain threshold, tests being conducted 60 min after the last treatment. Statistical analysis was done using analysis of variance followed by Dunnet's test. Results: Coadministration of buspirone with PCT attenuated the antinociceptive activity of PCT (P < 0.001), whereas fluoxetine + PCT increased pain threshold in the hot-plate and formalin test (P = 0.0046). Analgesic effect of PCT was not affected by ondansetron in formalin models. It attenuated analgesic action of PCT in hot-plate test (P = 0.0137). Conclusion: The results suggest that 5-HT1 receptors could also be responsible for the analgesic effect of PCT. Also, higher analgesia is produced by co-administration of SSRI (fluoxetine) + PCT. PMID:27298498

  10. 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 ...

  11. Cyp2D6 catalyzes 5-hydroxylation of 1-(2-pyrimidinyl)-piperazine, an active metabolite of several psychoactive drugs, in human liver microsomes.

    Science.gov (United States)

    Raghavan, Nirmala; Zhang, Donglu; Zhu, Mingshe; Zeng, Jianing; Christopher, Lisa

    2005-02-01

    1-(2-Pyrimidinyl)-piperazine (1-PP) is an active metabolite of several psychoactive drugs including buspirone. 1-PP is also the major metabolite in the human circulation and in rat brains following oral administration of buspirone. This study was conducted to identify the enzyme responsible for the metabolic conversion of 1-PP to 5-hydroxy-1-(2-pyrimidinyl)-piperazine (HO-1-PP) in human liver microsomes (HLMs). The product HO-1-PP was quantified by a validated liquid chromatography-tandem mass spectrometry method. In the presence of NADPH, 1-PP (100 microM) was incubated separately with human cDNA-expressed cytochrome P450 isozymes (including CYP2D6, 3A4, 1A2, 2A6, 2C9, 2C19, 2E1, and 2B6) at 37 degrees C. CYP2D6 catalyzed the formation of HO-1-PP from 1-PP. This catalytic activity was >95% inhibited by quinidine, a CYP2D6 inhibitor. HO-1-PP formation rates correlated well with the bufuralol 1-hydroxylase (CYP2D6) activities of individual HLMs. The formation of HO-1-PP followed a Michaelis-Menten kinetics with a K(m) of 171 microM and V(max) of 313 pmol/min x mg protein in HLMs. Collectively, these results indicate that polymorphic CYP2D6 is responsible for the conversion of 1-PP to HO-1-PP. PMID:15507542

  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. Screening of the antidepressant components in aqueous extract of detoxified cottonseeds

    International Nuclear Information System (INIS)

    Objective: To screen the antidepressant components in aqueous extract of detoxified cottonseeds (CTN). Methods: The synaptic membrane of rat cerebral cortex was extracted and incubated with CTN or its five flavonoid compounds (CTN-4, 7, 8, 9, 10) respectively. The adenylyl cyclase (AC) activity was measured by radioimmunoassay. Results: Just like the positive drug buspirone, a 5-HT1A receptor partial agonist, CTN and its five flavonoid compounds all activated AC in synaptic membrane in a dose-dependent manner, with compound CTN-8 being the most effective. Conclusion: The CTN-8, quercetin-3-O-apionyl-rutinoside, may be one of the most effective antidepressant components in CTN, and be a 5-HT1A receptor agonist. (authors)

  17. 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

    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.......The immune surveillance hypothesis suggests impaired immune responses to participate in development of cancer. This may partly be due to increased amounts of PGE2 and histamine, which inhibit cellular immunity. These effects are mediated by cAMP, which is increased and thereby may down-regulate IL...

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

    Science.gov (United States)

    Guy, A P; Gardner, C R

    1985-01-01

    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

  19. 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 fromcolon cancer patients compared to healthy blood donors. There was no effect of the immune modulating agents on PBMC from colon cancer patients....

  20. 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

  1. Quantification and pharmacokinetics of crizotinib in rats by liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Qiu, Feng; Gu, Yanan; Wang, Tingting; Gao, Yingying; Li, Xiao; Gao, Xiangyu; Cheng, Shan

    2016-06-01

    Crizotinib is a small molecule inhibitor of anaplastic lymphoma kinase (ALK) and can be used to treat ALK-positive nonsmall-cell lung cancer. A rapid and simple high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of crizotinib in rat plasma using a chemical synthetic compound buspirone as the internal standard (IS). The plasma samples were pretreated by a simple protein precipitation with methanol-acetonitrile (1:1, v/v). Chromatographic separation was successfully achieved on an Agilent Zorbax XDB C18 column (2.1 × 50 mm, 3.5 µm). The gradient elution system was composed of 0.1% formic acid aqueous solution and 0.1% formic acid in methanol solution. The flow rate was set at 0.50 mL/min. The multiple reaction monitoring was based on the transitions of m/z = 450.3 → 177.1 for crizotinib and 386.2 → 122.2 for buspirone (IS). The assay was successfully validated to demonstrate the selectivity, matrix effect, linearity, lower limit of quantification, accuracy, precision, recovery and stability according to the international guidelines. The lower limit of quantification was 1.00 ng/mL in 50 μL of rat plasma. This LC-MS/MS assay was successfully applied to the quantification and pharmacokinetic study of crizotinib in rats after intravenous and oral administration of crizotinib. The oral absolute bioavailability of crizotinib in rats was 68.6 ± 9.63%. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26467669

  2. Similar anxiolytic effects of agonists targeting serotonin 5-HT1A or cannabinoid CB receptors on zebrafish behavior in novel environments.

    Science.gov (United States)

    Connors, Kristin A; Valenti, Theodore W; Lawless, Kelly; Sackerman, James; Onaivi, Emmanuel S; Brooks, Bryan W; Gould, Georgianna G

    2014-06-01

    The discovery that selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine are present and bioaccumulate in aquatic ecosystems have spurred studies of fish serotonin transporters (SERTs) and changes in SSRI-sensitive behaviors as adverse outcomes relevant for risk assessment. Many SSRIs also act at serotonin 5-HT1A receptors. Since capitalizing on this action may improve treatments of clinical depression and other psychiatric disorders, novel multimodal drugs that agonize 5-HT1A and block SERT were introduced. In mammals both 5-HT1A and CB agonists, such as buspirone and WIN55,212-2, reduce anxious behaviors. Immunological and behavioral evidence suggests that 5-HT1A-like receptors may function similarly in zebrafish (Danio rerio), yet their pharmacological properties are not well characterized. Herein we compared the density of [(3)H] 8-hydroxy-2-di-n-propylamino tetralin (8-OH-DPAT) binding to 5-HT1A-like sites in the zebrafish brain, to that of similarly Gαi/o-coupled cannabinoid receptors. [(3)H] 8-OH-DPAT specific binding was 176±8, 275±32, and 230±36fmol/mg protein in the hypothalamus, optic tectum, and telencephalon. [(3)H] WIN55,212-2 binding density was higher in those same brain regions at 6±0.3, 5.5±0.4 and 7.3±0.3pm/mg protein. The aquatic light-dark plus maze was used to examine behavioral effects of 5-HT1A and CB receptor agonists on zebrafish novelty-based anxiety. With acute exposure to the 5-HT1A partial-agonist buspirone (50mg/L), or dietary exposure to WIN55,212-2 (7μg/week) zebrafish spent more time in and/or entered white arms more often than controls (pecological risks of azapirones and multimodal antidepressants in the future. PMID:24411165

  3. 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.

  4. 125I-Bolton-Hunter-8-methoxy-2-[N-propyl-N-propylamino]tetralin as a new selective radioligand of 5-HT1A sites in the rat brain. In vitro binding and autoradiographic studies

    International Nuclear Information System (INIS)

    In vitro binding assays with 125I-[8-methoxy-2-[N-propyl-N-(3'-iodo-4'-hydroxyphenyl)-propionamido -N'- propylamino] tetralin] (125I-BH-8-MeO-N-PAT), a 125I-labeled derivative of the potent serotonin (5-HT) agonist 8-hydroxy-2-[di-n-propylamino]tetralin [(3H]-8-OH-DPAT), showed that this compound recognized specific sites with nanomolar affinity for 5-HT and 5-HT1A ligands such as spiroxatrine, ipsapirone, buspirone and gepirone in rat hippocampal membranes. Comparison of the binding characteristics of 125I-BH-8-MeO-N-PAT with those of [3H]-8-OH-DPAT revealed striking similarities: at the hippocampal level, both binding sites exhibited nanomolar affinity for their respective ligands and the same Bmax; their pharmacological profiles defined by the inhibition of each bound ligand by a series of 26 serotonin, dopamine- or norepinephrine-related agonists and antagonists were identical; and their regional distributions examined by membrane binding assays and autoradiography of labeled brain sections were highly correlated. These observations indicate that 125I-BH-8-MeO-N-PAT is the first 125I-reversible ligand for the selective labeling of 5-HT1A sites in the rat central nervous system

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. 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

  12. 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.

  13. Review of pharmacokinetic and pharmacodynamic interaction studies with citalopram.

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    Brøsen, K; Naranjo, C A

    2001-08-01

    Citalopram is a selective serotonin reuptake inhibitor that is N-demethylated to N-desmethylcitalopram partially by CYP2C19 and partially by CYP3A4 and N-desmethylcitalopram is further N-demethylated by CYP2D6 to the likewise inactive metabolite di-desmethylcitalopram. The two metabolites are not active. The fact that citalopram is metabolised by more than one CYP means that inhibition of its biotransformation by other drugs is less likely. Besides citalopram has a wide margin of safety, so even if there was a considerable change in serum concentration then this would most likely not be of clinical importance. In vitro citalopram does not inhibit CYP or does so only very moderately. A number of studies in healthy subjects and patients have confirmed, that this also holds true in vivo. Thus no change in pharmacokinetics or only very small changes were observed when citalopram was given with CYP1A2 substrates (clozapine and therophylline), CYP2C9 (warfarin), CYP2C19 (imipramine and mephenytoin), CYP2D6 (sparteine, imipramine and amitriptyline) and CYP3A4 (carbamazepine and triazolam). At the pharmacodynamic level there have been a few documented cases of serotonin syndrome with citalopram and moclobemide and buspirone. It is concluded that citalopram is neither the source nor the cause of clinically important drug-drug interactions. PMID:11532381

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

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    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. [Treatment of generalized anxiety: new pharmacologic approaches].

    Science.gov (United States)

    Boulenger, J P

    1995-01-01

    First defined as a residual diagnostic category in the third edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM), Generalized Anxiety Disorder (GAD) was until recently one of the least studied and least clearly conceptualized of the anxiety disorders. The clinical definition of GAD has however improved up to the fourth edition of the DSM where the disorder is now characterized as a chronic state of apprehensive expectation and uncontrollable worry concerning multiple daily life events or activities and accompanied with at least 3 symptoms belonging to a list of six common manifestations of psychic or motor tension. Clinical research demonstrating the stability and the specificity of somatic symptoms clearly support the validity of the diagnosis of GAD despite possible difficulties in the differential diagnosis with other chronic conditions or axis II disorders such as dysthymia or mixed anxiety-depressive disorder. After benzodiazepines (BZD) and 5-HT1A agonists like buspirone, several other types of new anxiolytic drugs have been developed for the treatment of GAD. Partial agonists at GABA-BZD receptor sites may offer the advantage of a better efficacy vs side-effects ratio over classical BZDs; however, systematic comparative clinical trials will have to demonstrate the clinical relevance of the encouraging results obtained with these drugs, at the experimental level, during studies in healthy volunteers and during the first placebo-controlled trials. Furthermore, the recent description of GABA-receptor's subunits clearly suggest that the development of drugs acting at this level and devoided of psychomotor or withdrawal side-effects is a target that is worth pursuing. On the other hand, the development of 5-HT2 and 5-HT3 antagonists is also of interest for the treatment of GAD since it could provide new anxiolytic drugs without these side-effects and thus easier to administer on a long-term basis corresponding to the chronicity of GAD

  16. 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

  17. 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

  18. Pharmacological evaluation of novel 5-HT 3 receptor antagonist, QCM-13 (N-cyclohexyl-3-methoxyquinoxalin-2-carboxamide as anti-anxiety agent in behavioral test battery

    Directory of Open Access Journals (Sweden)

    Deepali Gupta

    2015-01-01

    Full Text Available Objective: In the last few decades, serotonin type-3 (5-HT 3 receptor antagonists have been identified as potential targets for anxiety disorders. In preclinical studies, 5-HT 3 antagonists have shown promising antianxiety effects. In this study, a novel 5-HT 3 receptor antagonist, QCM-13(N-cyclohexyl-3-methoxyquinoxalin-2-carboxamide was evaluated for anxiolytic-like activity in rodent behavioral test battery. Materials and Methods: Mice were given QCM-13 (2 and 4 mg/kg, intraperitoneally [i.p.] or diazepam (2 mg/kg, i.p. or vehicle and after 30 min, mice were subjected to four validated behavioral test batteries viz. elevated plus maze, hole board, light-dark and open field tests. Interaction study of QCM-13 with m-chlorophenyl piperazine (mCPP (mCPP, a 5-HT 2A/2C receptor agonist, 1 mg/kg, i.p. and buspirone (BUS, a partial 5-HT 1A agonist, 10 mg/kg, i.p. were performed to assess the pharmacological mechanism of the drug. Results: QCM-13 expressed potential anxiolytic effect with significant (P < 0.05 increase in behavioral parameters measured in aforementioned preliminary models. Besides, QCM-13 was unable to reverse the anxiogenic effect of mCPP, but potentiated anxiolytic affect of BUS. Conclusion: The results suggest that QCM-13 can be a potential therapeutic candidate for the management of anxiety-like disorders and combination doses of novel 5-HT 3 receptor antagonist with standard anxiolytics may improve therapeutic efficacy.

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

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    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

  20. 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

  1. An Orally Active Phenylaminotetralin-Chemotype Serotonin 5-HT7 and 5-HT1A Receptor Partial Agonist that Corrects Motor Stereotypy in Mouse Models.

    Science.gov (United States)

    Canal, Clinton E; Felsing, Daniel E; Liu, Yue; Zhu, Wanying; Wood, JodiAnne T; Perry, Charles K; Vemula, Rajender; Booth, Raymond G

    2015-07-15

    Stereotypy (e.g., repetitive hand waving) is a key phenotype of autism spectrum disorder, Fragile X and Rett syndromes, and other neuropsychiatric disorders, and its severity correlates with cognitive and attention deficits. There are no effective treatments, however, for stereotypy. Perturbation of serotonin (5-HT) neurotransmission contributes to stereotypy, suggesting that distinct 5-HT receptors may be pharmacotherapeutic targets to treat stereotypy and related neuropsychiatric symptoms. For example, preclinical studies indicate that 5-HT7 receptor activation corrects deficits in mouse models of Fragile X and Rett syndromes, and clinical trials for autism are underway with buspirone, a 5-HT1A partial agonist with relevant affinity at 5-HT7 receptors. Herein, we report the synthesis, in vitro molecular pharmacology, behavioral pharmacology, and pharmacokinetic parameters in mice after subcutaneous and oral administration of (+)-5-(2'-fluorophenyl)-N,N-dimethyl-1,2,3,4-tetrahydronaphthalen-2-amine ((+)-5-FPT), a new, dual partial agonist targeting both 5-HT7 (Ki = 5.8 nM, EC50 = 34 nM) and 5-HT1A (Ki = 22 nM, EC50 = 40 nM) receptors. Three unique, heterogeneous mouse models were used to assess the efficacy of (+)-5-FPT to reduce stereotypy: idiopathic jumping in C58/J mice, repetitive body rotations in C57BL/6J mice treated with the NMDA antagonist, MK-801, and repetitive head twitching in C57BL/6J mice treated with the 5-HT2 agonist, DOI. Systemic (+)-5-FPT potently and efficaciously reduced or eliminated stereotypy in each of the mouse models without altering locomotor behavior on its own, and additional tests showed that (+)-5-FPT, at the highest behaviorally active dose tested, enhanced social interaction and did not cause behaviors indicative of serotonin syndrome. These data suggest that (+)-5-FPT is a promising medication for treating stereotypy in psychiatric disorders. PMID:26011730

  2. Antagonism by 8-hydroxy-2(di-n-propylamino)tetraline and other serotonin agonists of muscarinic M1-type receptors coupled to inositol phospholipid breakdown in human IMR-32 and SK-N-MC neuroblastoma cells

    International Nuclear Information System (INIS)

    IMR-32 and SK-N-MC cells were found to contain [3H]quinuclidinyl benzilate specific binding sites inhibited by pirenzepine in a manner suggesting the presence of both M1-type and M2-type muscarinic receptor recognition sites. Neither cell had detectable [3H]8-OH-DPAT binding sites. Carbachol stimulated the rate of inositol phospholipid breakdown in IMR-32 and SK-N-MC human neuroblastoma cells with an EC50 value of about 50 μM in both cases. Pirenzepine inhibited the carbachol stimulated inositol phospholipid breakdown in both cells with Hill slopes of unity and IC50 values of 15 nM (IMR-32) and 12 nM (SK-N-MC). The 5-HT1A receptor agonist 8-OH-DPAT competitively inhibited carbachol-stimulated inositol phospholipid breakdown with pA2 values of 5.78 (IMR-32) and 5.61 (SK-N-MC). The 5-HT agonists 5-MeODMT and buspirone at micromolar concentrations inhibited carbachol-stimulated breakdown in IMR-32 cells. The inhibition by 8-OH-DPAT and 5-MeODMT was not affected by preincubation with (-)alprenolol. 5-HT was without effect on either basal or carbachol-stimulated breakdown. It is concluded that IMR-32 and SK-N-MC neuroblastoma cells express muscarinic M1-type but not serotoninergic receptors coupled to phosphoinositide-specific phospholipase C. 8-OH-DPAT acts as a weak antagonist at these muscarinic receptors

  3. 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

  4. 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. PMID:22348413

  5. 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

  6. Prevalence of ergot derivatives in natural ryegrass pastures: detection and pathogenicity in the horse.

    Science.gov (United States)

    Lezica, F P; Filip, R; Gorzalczany, S; Ferraro, G; de Erausquin, G A; Rivas, C; Ladaga, G J B

    2009-02-01

    In the present study, we determined the incidence and effects of season and weather on clinical manifestations of endophyte-infected ryegrass toxicity, performed chemical detection and pharmacological bioassays on ryegrass extracts, and conducted trials on: (i) effects of domperidone or metochlopramide on ovarian inactivity induced by endophyte-infected ryegrass; (ii) efficacy of buspirone or dihydrochloro phenyl piperazine (m-CPP) for preventing suppressed milk production induced by endophyte-infected ryegrass; and (iii) efficacy of domperidone to induce ovulation during winter anestrus. Mares with toxicosis had prolonged gestation, embryonic losses, dystocia, poor mammary gland development, low milk production, prolonged uterine involution, and suppressed ovarian activity. Foals had respiratory failure, abnormalities of the skin, umbilicus, bone, and muscle, failure to thrive, blindness, testicular atrophy, and decreased serum total immunoglobulin concentrations. Endophyte-infected ryegrass and the incidence of toxicosis were correlated (r=0.861, P=0.03). Ergot alkaloids were not detected in extracts of endophyte-infected ryegrass by either thin-layer chromatography or spectrophotometry, but their presence was inferred in bioassays of extracts (dose-related increases in the contractile response of rat uterus). Mares given metoclopropamide (0.6 mg/kg/d), given orally every 8h for up to 7d) ovulated earlier (4-7d vs. 15-18d, Pmilk production, the latter did not induce ovarian cyclicity in healthy mares during seasonal anestrus. Based on these findings, we inferred that endophyte-infected ryegrass is associated with ergot alkaloid intoxication in horse. PMID:18823653

  7. 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.

  8. Determination of astragaloside III in rat plasma by liquid chromatography-tandem mass spectrometry and its application to a rat pharmacokinetic study.

    Science.gov (United States)

    Zhai, Yongsong; Li, Pengyue; Wang, Manyuan; Gong, Muxin; Qiu, Feng

    2016-02-01

    Astragaloside III (AST III), a naturally occurring saponin compound isolated from Radix Astragali, has been demonstrated to have anti-gastric ulcer, immunomodulatory and antitumor effects. To evaluate its pharmacokinetics in rats, a rapid, sensitive and specific high-performance liquid chromatography-tandem mass spectrometric (HPLC-MS/MS) method has been developed and validated for the quantification of astragaloside III in rat plasma. Samples were pretreated using a simple protein precipitation with methanol-acetonitrile (50:50, v/v) and the chromatographic separation was performed on a C18 column by a gradient elution using a mobile phase consisting of water containing 0.1% formic acid and acetonitrile containing 0.1% formic acid. Astragaloside III and the internal standard (buspirone) were detected using a tandem mass spectrometer in positive multiple reaction monitoring mode. Method validation revealed excellent linearity over the range of 5.00-5000 ng/mL together with satisfactory intra- and inter-day precision, accuracy and recovery. Stability testing showed that astragaloside III spiked into rat plasma was stable for 24 h at 20°C temperature, for up to 30 days at -80°C, and during three freeze-thaw cycles. The method was successfully used to investigate the pharmacokinetic profile of AST III after oral (10 mg/kg) and intravenous (1.0 mg/kg) administration in rats. The oral absolute bioavailability of AST III was calculated to be 4.15 ± 0.67% with an elimination half-life value of 2.13 ± 0.11 h, suggesting its poor absorption and/or strong metabolism in vivo. PMID:26031660

  9. 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

  10. 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

  11. Neuropharmacological and physiological validation of a computer-controlled two-compartment black and white box for the assessment of anxiety.

    Science.gov (United States)

    Onaivi, E S; Martin, B R

    1989-01-01

    1. The two-compartment black and white box first described by Crawley and Goodwin (1980) has been used to study anti-anxiety properties of drugs but has not been validated. 2. An automated test system and validation of the protocol for the evaluation of compounds with anxiolytic or anxiogenic potential is described. 3. The box is partitioned into black and white sections with an interconnecting opening and is equipped with micro-switch photoelectric controls (light source and photoreceiver) and an interface connected to the menu-driven computer during anxiety testing. 4. Plasma corticosterone levels in naive mice maintained on a reversed L:D cycle was significantly reduced following restricted exposure to the brightly lit white section but not in the red-illuminated black section. 5. The optimal structural configuration in different test situations was found to be a square rather than a round box. 6. Under normal conditions, mice spend about 60% of the time in the dark compartment so that the exploratory activities and time spent in the white section are taken as a measure of anxiety. 7. Compounds examined included the reference anxiolytic diazepam, nicotine, naloxone, MDL 72222, ICS 205 930 and buspirone, all of which increased mouse exploratory activities in the white section. PTZ, beta-CCP, morphine and amphetamine increased exploration in the black compartment and reduced exploration in the white area. 8. Fluphenazine and imipramine had no specific effects on anxiety responding, although the cataleptogenic effect of fluphenazine was apparent. 9. Daily repeated testing was possible with a maximum of up to four trials a week using naive animals during the 5-min test session. 10. The results suggest that the rapid and automated test system for the assessment of changes in measures of anxiety is not only valid for large scale evaluation of compounds but could be used to elucidate mechanisms of drug action and the CNS pathways linked with anxiolysis and

  12. 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

  13. 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.

  14. Breakthrough seizures after starting vilazodone for depression.

    Science.gov (United States)

    McKean, James; Watts, Hannah; Mokszycki, Robert

    2015-03-01

    Vilazodone is a new selective serotonin reuptake inhibitor (SSRI) and serotonin 5-HT1a partial agonist that is approved by the United States Food and Drug Administration to treat major depression. SSRI-induced seizures are rare and are more likely to be associated with larger doses and severe symptoms such as those present in serotonin syndrome. Several case reports have implicated SSRIs, buspirone, or the combination of these agents as the cause of seizures, but these reports were confounded with either coingestions or doses that exceeded FDA recommendations. We describe a 22-year-old woman with a history of seizure disorder who had been seizure free for the previous 8 years and experienced two breakthrough seizures shortly after starting vilazodone. Her dose of vilazodone had recently been titrated to 40 mg/day when she experienced the first seizure. She was instructed to taper vilazodone over the next several days, then discontinue the drug, and then follow up with her neurologist. Based on the patient's history, physical examination, and recent dose increase, it was plausible that vilazodone was the cause of the seizures. Use of the Naranjo adverse drug reaction probability scale indicated a possible relationship (score of 4) between her development of seizures and vilazodone therapy. The pharmacodynamics of this particular class of SSRI has both proconvulsive and anticonvulsive mechanisms. This is of particular concern in patients with a history of seizure disorder who are starting antidepressive therapy. In persons with epilepsy who are taking vilazodone and experience breakthrough seizures, practitioners should consider this drug as a potential cause of these seizures. Thus, until future research and experience with vilazodone can provide a definitive answer, clinicians should be cautious when prescribing this medication to treat depression in patients with a history of seizure disorder. PMID:25809181

  15. 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

  16. Evaluating antidepressant treatment prior to adding second-line therapies among patients with treatment-resistant depression.

    Science.gov (United States)

    Hassan, Amany K; Farmer, Kevin C; Brahm, Nancy C; Neas, Barbara R

    2016-04-01

    Background Patients with depression can be mistakenly labeled as treatment-resistant if they fail to receive an adequate first-line antidepressant trial. Adding second-line agents to the treatment regimens can create an additional burden on both the patients and the healthcare system. Objectives To determine if depressed patients receive an adequate antidepressant trial prior to starting second-line therapy and to investigate the association between the type of second-line treatment and severity of illness or depression among unipolar versus bipolar patients. Setting Oklahoma Medicaid claims data between 2006 and 2011. Methods Subjects were depression-diagnosed adult patients with at least two prescriptions of antidepressants followed by a second-line agent. Patients were categorized into one of three groups: an atypical antipsychotic, other augmentation agents (lithium, buspirone, and triiodothyronine), or adding antidepressants, based on the type of second-line therapy. An adequate trial was defined per the American Psychiatric Association guidelines. Factors associated with the type of treatment were tested using multinomial logistic regression models stratified by type of depression (unipolar vs. bipolar patients). Main outcome measure Variables used to measure receiving an adequate antidepressant trial included: trial duration, adherence, dose adequacy, and number of distinct antidepressant trials. Results A total of 3910 patients were included in the analysis. Most subjects reached the recommended antidepressant dose. However, 28 % of patients had an antidepressant trial duration depression. These findings support policies that require reviewing the recommended dose and duration of the first-line antidepressant before adding second-line agents. Healthcare providers need to review the patient's history and reconsider the evidence for prescribing second-line agents. PMID:26935957

  17. N-dealkylation of arylpiperazine derivatives: disposition and metabolism of the 1-aryl-piperazines formed.

    Science.gov (United States)

    Caccia, Silvio

    2007-08-01

    In recent years several arylpiperazine derivatives have reached the stage of clinical application, mainly for the treatment of depression, psychosis or anxiety. Examples are the pyrimidinylpiperazine buspirone, the chlorophenylpiperazine derivatives nefazodone and trazodone, the dichlorophenylpiperazine aripiprazole and the benzisothiazolyl derivatives perospirone and ziprasidone. Most of them undergo extensive pre-systemic and systemic metabolism including CYP3A4-dependent N-dealkylation to 1-aryl-piperazines. These metabolites are best known for the variety of serotonin receptor-related effects they cause in man and animals, although some have affinity for other neurotransmitter receptors; others, however, are still largely unexplored despite uncontrolled use as amphetamine-like designer drugs. Once formed they distribute extensively in tissues, including brain which is the target site of most arylpiperazine derivatives, and are then primarily biotransformed by CYP2D6-dependent oxidation to hydroxylates which are excreted as conjugates; only 1-(2-benzisothiazolyl)-piperazine is more susceptible to sulfur oxidation than to aromatic hydroxylation. In studies analysing animal brain and human blood, 1-aryl-piperazine concentrations were either higher or lower than the parent compound(s), although information is available only for some derivatives. At steady state, the metabolite-to-parent drug ratios varied widely among individuals taking the same dosage of the same arylpiperazine derivative. This is consistent with the known individual variability in the expression and activity of CYP3A4 and CYP2D6. This review also surveys current published information on physiological and pathological factors affecting the 1-aryl-piperazine-to-parent drug ratios and examines the potential role of 1-aryl-piperazine formation in the pharmacological actions of the arylpiperazine derivatives that are already or will shortly be available in major markets. PMID:17691920

  18. 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

  19. AVN-211, Novel and Highly Selective 5-HT6 Receptor Small Molecule Antagonist, for the Treatment of Alzheimer's Disease.

    Science.gov (United States)

    Ivachtchenko, Alexandre V; Lavrovsky, Yan; Ivanenkov, Yan A

    2016-03-01

    Within the past decade several novel targets have been indicated as key players in Alzheimer-type dementia and associated conditions, including a "frightening" memory loss as well as severe cognitive impairments. These proteins are deeply implicated in crucial cell processes, e.g., autophagy, growth and progression, apoptosis, and metabolic equilibrium. Since recently, 5-HT6R has been considered as one of the most prominent biological targets in AD drug therapy. Therefore, we investigated the potential procognitive and neuroprotective effects of our novel selective 5-HT6R antagonist, AVN-211. During an extensive preclinical evaluation the lead compound demonstrated a relatively high therapeutic potential and improved selectivity toward 5-HT6R as compared to reference drug candidates. It was thoroughly examined in different in vivo behavioral models directly related to AD and showed evident improvements in cognition and learning. In many cases, the observed effect was considerably greater than that determined for the reported drugs and drug candidates, including memantine, SB-742457, and Lu AE58054, evaluated under the same conditions. In addition, AVN-211 showed a similar or better anxiolytic efficacy than fenobam, rufinamide, lorazepam, and buspirone in an elevated plus-maze model, elevated platform, and open field tests. The compound demonstrated low toxicity and no side effects in vivo, an appropriate pharmacokinetic profile, and stability. In conclusion, AVN-211 significantly delayed or partially halted the progressive decline in memory function associated with AD, which makes it an interesting drug candidate for the treatment of neurodegenerative and psychiatric disorders. Advanced clinical trials are currently under active discussion and in high priority. PMID:26886442

  20. 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

  1. 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

  2. Clinical drugs that interact with St. John's wort and implication in drug development.

    Science.gov (United States)

    Di, Yuan Ming; Li, Chun Guang; Xue, Charlie Changli; Zhou, Shu-Feng

    2008-01-01

    St. John's wort (Hypericum perforatum, SJW) is one of the most commonly used herbal antidepressants for the treatment of minor to moderate depression. A major safety concern about SJW is its ability to alter the pharmacokinetics and/or clinical response of a variety of clinically important drugs that have distinctive chemical structure, mechanism of action and metabolic pathways. This review highlights and updates the knowledge on clinical interactions of prescribed drugs with SJW and the implication in drug development. A number of clinically significant interactions of SJW have been identified with conventional drugs, including anticancer agents (imatinib and irinotecan), anti-HIV agents (e.g. indinavir, lamivudine and nevirapine), anti-inflammatory agents (e.g. ibuprofen and fexofenadine), antimicrobial agents (e.g. erythromycin and voriconazole), cardiovascular drugs (e.g. digoxin, ivabradine, warfarin, verapamil, nifedipine and talinolol), central nervous system agents (e.g. amitriptyline, buspirone, phenytoin, methadone, midazolam, alprazolam, and sertraline), hypoglycaemic agents (e.g. tolbutamide and gliclazide), immuno-modulating agents (e.g. cyclosporine and tacrolimus), oral contraceptives, proton pump inhibitor (e.g. omeprazole), respiratory system agent (e.g. theophylline), statins (e.g. atorvastatin and pravastatin). Both pharmacokinetic and pharmacodynamic components may play a role in the interactions of drugs with SJW. For pharmacokinetic changes of drugs by SJW, induction of cytochrome P450s (e.g. CYP2C9 and 3A4) and P-glycoprotein (P-gp) are considered the major mechanism. Thus, it is not a surprise that many drugs that interact with SJW are substrates of CYP3A4, CYP2C9 and P-gp. A comprehensive understanding of clinical drugs that interact with SJW has important implications in drug development. New drugs may be designed to minimize interactions with SJW; and new SJW formulations may be designed to avoid drug interactions. Further clinical and

  3. 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

  4. Use of PET and the radioligand [carbonyl-11C]WAY-100635 in psychotropic drug development

    International Nuclear Information System (INIS)

    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-hydroxytryptamine1A (5-HT1A) receptor is of central interest as a target for the treatment of anxiety, depression, and schizophrenia. Research on the clinical significance of the 5-HT1A receptor now benefits from the highly selective radioligand [carbonyl-11C]WAY-100635 (WAY) for quantitative determination of 5-HT1A 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-HT1A 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-HT1A receptors in the primate brain. Pindolol is an β-adrenoreceptor antagonist with a high affinity to 5-HT1A 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-HT1A 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-HT1A receptor antagonist and putative drug with implications for the treatment of depression. In the cynomolgus monkey brain, robalzotan in the dose range 2-100 μg/kg IV occupied 5-HT1A receptors in a dose-dependent and saturable manner with a maximal calculated occupancy of 70-80%. The relationship

  5. 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

  6. 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.

  7. 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.

  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