Sample records for buspirone

  1. Buspirone, a novel nonbenzodiazepine anxiolytic. (United States)

    Kastenholz, K V; Crismon, M L


    The chemistry, pharmacology, pharmacokinetics, clinical efficacy, adverse effects, dosage, administration, and availability of buspirone hydrochloride, a novel nonbenzodiazepine anxiolytic, are reviewed. Buspirone hydrochloride is an azaspirodecanedione anxiolytic. The exact mechanism of its anxiolytic action is unknown. It does not appear to influence the benzodiazepine-gamma-aminobutyric acid-chloride ionophore complex as the benzodiazepines do. It antagonizes striatal-dopamine autoreceptors, and it may act as a midbrain modulator exerting selective anxiolytic activity. Buspirone is rapidly absorbed after oral administration. Administration with food appears to slow the rate of drug absorption and increase the amount of unchanged drug reaching the systemic circulation. Buspirone's elimination half-life is 2.5-3 hours. It is extensively metabolized, with less than 1% of an administered dose excreted as unchanged drug. The contribution of its metabolites to its anxiolytic effects is unknown. Buspirone has been shown to be as effective as diazepam and clorazepate and more effective than placebo in the treatment of generalized anxiety. Buspirone lacks the sedative, muscle relaxant, and anticonvulsive effects of the benzodiazepines. Its adverse effects are minimal, with dizziness, nervousness, and headaches as the most common side effects. Buspirone does not impair driving skills, interact with alcohol or concomitant medications, or produce physiologic dependence. It appears to have little potential for abuse. The average daily adult dose is 15-20 mg. Buspirone hydrochloride is an effective drug in the treatment of generalized anxiety disorder that is comparable with the conventional benzodiazepine anxiolytics.

  2. Compound list: buspirone [Open TG-GATEs

    Lifescience Database Archive (English)

    Full Text Available buspirone BPR 00173 ...

  3. Comparison of buspirone in two separate studies. (United States)

    Goldberg, H L; Finnerty, R


    Two double-blind studies are described in which buspirone was compared with placebo and diazepam (Study A) or clorazepate (Study B) in outpatients with moderate to severe anxiety. Results, assessed on the Hamilton Rating Scales for Depression and Anxiety, the SCL-56, the Profile of Mood States, and the Covi and Raskin scales, indicated that buspirone consistently relieved both anxiety and associated depression. In Study B, trends in favor of buspirone were seen on several SCL-56 items and the Hamilton somatic factor; significant differences in this direction were found for several POMS items. Sedation was seen less often with buspirone than either diazepam or clorazepate.

  4. Pharmacokinetics of buspirone in autistic children. (United States)

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


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

  5. Effects of buspirone on dopamine dependent behaviours in rats. (United States)

    Dhavalshankh, A G; Jadhav, S A; Gaikwad, R V; Gaonkar, R K; Thorat, V M; Balsara, J J


    Buspirone, a partial agonist of 5-hydroxytryptamine autoreceptors, selectively blocks presynaptic nigrostriatal D2 dopamine (DA) autoreceptors. At doses which antagonised action of apomorphine in biochemical presynaptic nigrostriatal D2 DA autoreceptor test systems buspirone neither induced catalepsy nor antagonised apomorphine-induced turning behaviour in rats indicating that at these doses buspirone does not block postsynaptic striatal D2 and D1 DA receptors. This study determines whether at high doses buspirone blocks postsynaptic striatal D2 and D1 DA receptors and provides behavioural evidence for selective blockade of presynaptic nigrostriatal D2 DA autoreceptors by smaller doses of buspirone. We investigated in rats whether buspirone induces catalepsy and effect of its pretreatment on DA agonist induced oral stereotypies and on cataleptic effect of haloperidol and small doses (0.05, 0.1 mg/kg, ip) of apomorphine. Buspirone at 1.25, 2.5, 5 mg/kg, ip neither induced catalepsy nor antagonised apomorphine stereotypy but did potentiate dexamphetamine stereotypy and antagonised cataleptic effect of haloperidol and small doses of apomorphine. Buspirone at 10, 20, 40 mg/kg, ip induced catalepsy and antagonised apomorphine and dexamphetamine stereotypies. Our results indicate that buspirone at 1.25, 2.5, 5 mg/kg blocks only presynaptic nigrostriatal D2 DA autoreceptors while at 10, 20, 40 mg/kg, it blocks postsynaptic striatal D2 and D1 DA receptors. Furthermore, buspirone at 1.25, 2.5, 5 mg/kg by selectively blocking presynaptic nigrostriatal D2 DA autoreceptors, increases synthesis of DA and makes more DA available for release by dexamphetamine and during haloperidol-induced compensatory 'feedback' increase of nigrostriatal DAergic neuronal activity and thus potentiates dexamphetamine stereotypy and antagonizes haloperidol catalepsy.

  6. Possible modulation of the antidiabetic effect of rosiglitazone by buspirone

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    Wafaa R. Mohamed


    Full Text Available Diabetes mellitus (DM is a group of metabolic disorders characterized by chronic hyperglycemia resulting from relative or absolute insulin deficiency with or without insulin resistance. As anxiolytics may have influence on glycemic control in diabetics, the present study was conducted to investigate the possible influence of buspirone in streptozotocin-induced DM and its possible interactions with rosiglitazone, an insulin sensitizer. Diabetes was induced by streptozotocin (50 mg/kg i.p.. Rats were classified into five groups namely: normal control, diabetic control, rosiglitazone (10 mg/kg p.o., buspirone (20 mg/kg i.p. or combination of both rosiglitazone and buspirone, respectively. All groups received daily treatments for 2 weeks after induction of DM including the normal group which received 1% Tween 80. There was no significant interaction between rosiglitazone and buspirone on the levels of serum glucose, insulin and C-peptide or liver glycogen content. Similarly, no interaction was observed between rosiglitazone and buspirone on oxidative stress parameters including serum malondialdehyde and blood glutathione levels or blood superoxide dismutase activity. In conclusion, the present study revealed that co-administration of buspirone with rosiglitazone does not produce serious reactions and buspirone can be safely administered as an anxiolytic in diabetic patients treated with rosiglitazone.

  7. Behavioral Studies on the Mechanism of Buspirone, an Atypical Anti-Anxiety Drug (United States)


    diazepam ; a benzodiazepine) , currently the most widely prescribed anxiolytic on the market (Goldberg & Finnerty, 1979; 1982); however, those of the benzodiazepine, chlordiazepoxide . However, unlike the benzodiazepines, effects of buspirone were not reversible by the...efficacy of buspirone and diazepam in the treatment of anxiety. Affierican Journal of Psychiatry, 1979, ~, 1184-1187. Goldberg, H. L. & Finnerty, R

  8. Iontophoretic transdermal delivery of buspirone hydrochloride in hairless mouse skin. (United States)

    Al-Khalili, Mohammad; Meidan, Victor M; Michniak, Bozena B


    The transdermal delivery of buspirone hydrochloride across hairless mouse skin and the combined effect of iontophoresis and terpene enhancers were evaluated in vitro using Franz diffusion cells. Iontophoretic delivery was optimized by evaluating the effect of drug concentration, current density, and pH of the vehicle solution. Increasing the current density from 0.05 to 0.1 mA/cm2 resulted in doubling of the iontophoretic flux of buspirone hydrochloride, while increasing drug concentration from 1% to 2% had no effect on flux. Using phosphate buffer to adjust the pH of the drug solution decreased the buspirone hydrochloride iontophoretic flux relative to water solutions. Incorporating buspirone hydrochloride into ethanol:water (50:50 vol/vol) based gel formulations using carboxymethylcellulose and hydroxypropylmethylcellulose had no effect on iontophoretic delivery. Incorporation of three terpene enhancers (menthol, cineole, and terpineol) into the gel resulted in a synergistic effect when combined with iontophoresis. Menthol was the most active enhancer, and when combined with iontophoresis it was possible to deliver 10 mg/cm2/day of buspirone hydrochloride.

  9. Dose-dependent response of central dopaminergic systems to buspirone in mice. (United States)

    Jadhav, S A; Gaikwad, R V; Gaonkar, R K; Thorat, V M; Gursale, S C; Balsara, J J


    Buspirone, a partial agonist of 5-hydroxytryptaminelA autoreceptors, preferentially blocks the presynaptic rather than the postsynaptic D2 dopamine (DA) receptors. Behavioural effects of a wide dose range of buspirone were therefore studied in mice. Buspirone at 0.625 to 5 mg/kg ip induced stereotyped cage climbing behaviour which was antagonized by pretreatment with haloperidol, alpha-methyl-p-tyrosine and small doses of apomorphine. Buspirone at 10, 20 and 40 mg/kg ip induced catalepsy and antagonized oral stereotypies induced by high doses of apomorphine and methamphetamine and apomorphine-induced cage climbing behaviour. The findings indicate that buspirone at 0.625 to 5 mg/kg selectively blocks the presynaptic mesolimbic D2 DA autoreceptors and releases DA which stimulates the postsynaptic mesolimbic D2 and D1 DA receptors and induces cage climbing behaviour. Buspirone, at 10, 20 and 40 mg/kg blocks the postsynaptic striatal and mesolimbic D2 and D1 DA receptors. Pretreatment with 1-tryptophan, dexfenfluramine and fluoxetine antagonized buspirone induced cage climbing behaviour and potentiated buspirone induced catalepsy. Pretreatment with trazodone, mianserin and p-chlorophenylalanine potentiated buspirone induced cage climbing behaviour and antagonized buspirone induced catalepsy. The results indicate that drugs which influence the activity of central serotonergic systems modulate the intensity of buspirone induced cage climbing behaviour and catalepsy.

  10. Review of the side-effect profile of buspirone. (United States)

    Newton, R E; Marunycz, J D; Alderdice, M T; Napoliello, M J


    In 984 patients with generalized anxiety disorder who received buspirone in double-blind studies, the incidence of drowsiness (9 percent) did not differ significantly from that (10 percent) reported in 334 patients who received placebo. A probability value of p less than or equal to 0.10 was the criterion for significance. The incidence of drowsiness in buspirone-treated patients was significantly less than that in each of the groups receiving diazepam (32 percent), clorazepate (26 percent), lorazepam (58 percent), or alprazolam (43 percent). The side effects that did occur significantly more frequently in the buspirone group than in the placebo group were dizziness (9 percent versus 2 percent), headache (7 percent versus 2 percent), nervousness (4 percent versus 1 percent), light-headedness (4 percent versus less than 1 percent), diarrhea (3 percent versus less than 1 percent), paresthesia (2 percent versus less than 1 percent), excitation (2 percent versus less than 1 percent), and sweating/clamminess (1 percent versus 0 percent). The severities of these effects were predominantly rated as only mild or moderate. Fatigue occurred less frequently in buspirone-treated patients than in those receiving any of the benzodiazepines, and weakness occurred more frequently in diazepam-treated patients. Depression occurred less frequently in buspirone-treated patients than in those receiving clorazepate, diazepam, or lorazepam. Impotence occurred only in clorazepate- and lorazepam-treated patients. Decreased libido occurred more frequently in diazepam-treated patients, whereas increased libido was more frequent in clorazepate-treated patients. Nausea was reported more frequently in buspirone-treated patients than in those receiving clorazepate, diazepam, or alprazolam; diarrhea occurred more frequently in the buspirone group than in the diazepam group. The mean daily doses of the various treatments were buspirone, 20 mg; diazepam, 20 mg; clorazepate, 24 mg; lorazepam, 3 mg

  11. The side effect profile of buspirone in comparison to active controls and placebo. (United States)

    Newton, R E; Casten, G P; Alms, D R; Benes, C O; Marunycz, J D


    Animal studies and the original study comparing buspirone with diazepam and placebo indicated that sedative-hypnotic side effects and impairment in psychomotor function would be less with buspirone than with diazepam. This was borne out by the present double-blind study in which almost 700 patients received buspirone. Mean daily doses were buspirone, 20 mg; diazepam, 20 mg; and clorazepate, 24 mg. Sedation, lethargy, and depression were significantly less with buspirone than with diazepam or clorazepate and were comparable to placebo. There was no indication that other types of side effects would differ significantly from those seen with the benzodiazepines. Nervousness, headache, and dizziness were experienced more frequently with buspirone than with placebo.

  12. Buspirone: review of its pharmacology and current perspectives on its mechanism of action. (United States)

    Eison, A S; Temple, D L


    Buspirone is a novel anxiolytic agent unrelated to the benzodiazepines in structure or pharmacologic properties. Extensive clinical studies have shown buspirone to be effective in the treatment of anxiety, with efficacy comparable to diazepam or clorazepate. Buspirone exhibits a unique pharmacologic profile in that it alleviates anxiety without causing sedation or functional impairment and does not promote abuse or physical dependence. Furthermore, preclinical studies have shown that buspirone does not possess anticonvulsant or muscle relaxant properties and does not interact significantly with central nervous system depressants. Biochemical and electrophysiologic studies indicate that buspirone alters monoaminergic and GABAergic systems in a manner different from that of the benzodiazepines. The uniform depressant action of the benzodiazepines upon serotonergic, noradrenergic, and dopaminergic cell firing may result from their facilitatory effect on gamma-aminobutyric acid and its known inhibitory influence in these monoaminergic areas. Unlike the benzodiazepines, buspirone exerts a differential influence upon monoaminergic neuronal activity, suppressing serotonergic activity while enhancing dopaminergic and noradrenergic cell firing. The mechanism of action of buspirone challenges the notion that only one neurotransmitter mediates anxiety. The interaction with multiple neurotransmitters at multiple brain sites suggests that buspirone may alter diverse activities within a "neural matrix of anxiety." In contrast to the benzodiazepines, buspirone orchestrates activity within this neural matrix to achieve effective treatment of anxiety while preserving arousal and attentional processes.

  13. The molecular interactions of buspirone analogues with the serotonin transporter. (United States)

    Jarończyk, Małgorzata; Chilmonczyk, Zdzisław; Mazurek, Aleksander P; Nowak, Gabriel; Ravna, Aina W; Kristiansen, Kurt; Sylte, Ingebrigt


    A major problem with the selective serotonin reuptake inhibitors (SSRIs) is the delayed onset of action. A reason for that may be that the initial SSRI-induced increase in serotonin levels activates somatodendritic 5-HT(1A) autoreceptors, causing a decrease in serotonin release in major forebrain areas. It has been suggested that compounds combining inhibition of the serotonin transport protein with antagonistic effects on the 5-HT(1A) receptor will shorten the onset time. The anxiolytic drug buspirone is known as 5-HT(1A) partial agonist. In the present work, we are studying the inhibition of the serotonin transporter protein by a series of buspirone analogues by molecular modelling and by experimental affinity measurements. Models of the transporter protein were constructed using the crystal structure of the Escherichia coli major facilitator family transporter-LacY and the X-ray structure of the neurotransmitter symporter family (NSS) transporter-LeuT(Aa) as templates. The buspirone analogues were docked into both SERT models and the interactions with amino acids within the protein were analyzed. Two putative binding sites were identified on the LeuT(Aa) based model, one suggested to be a high-affinity site, and the other suggested to be a low-affinity binding site. Molecular dynamic simulations of the LacY based model in complex with ligands did not induce a helical architecture of the LacY based model into an arrangement more similar to that of the LeuT(Aa) based model.

  14. Buspirone versus Methylphenidate in the Treatment of Attention Deficit Hyperactivity Disorder: A Double-Blind and Randomized Trial (United States)

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


    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…

  15. Buspirone. A preliminary review of its pharmacological properties and therapeutic efficacy as an anxiolytic. (United States)

    Goa, K L; Ward, A


    Buspirone hydrochloride (HCl)1 is a new anxiolytic with a unique chemical structure. Its mechanism of action remains to be elucidated. Unlike the benzodiazepines, buspirone lacks hypnotic, anticonvulsant and muscle relaxant properties, and hence has been termed 'anxioselective'. As evidenced by a few double-blind clinical trials, buspirone 15 to 30 mg/day improves symptoms of anxiety assessed by standard rating scales similarly to diazepam, clorazepate, alprazolam and lorazepam. Like diazepam, buspirone is effective in patients with mixed anxiety/depression, although the number of patients studied to date is small. In several studies, a 'lagtime' of 1 to 2 weeks to the onset of anxiolytic effect has been noted; hence motivation of patient compliance may be necessary. Sedation occurs much less often after buspirone than after the benzodiazepines; other side effects are minor and infrequent. In healthy volunteers, buspirone does not impair psychomotor or cognitive function, and appears to have no additive effect with alcohol. Early evidence suggests that buspirone has limited potential for abuse and dependence. Thus, although only wider clinical use for longer periods of time will more clearly define some elements of its pharmacological profile, with its low incidence of sedation buspirone is a useful addition to the treatments available for generalised anxiety. It may well become the preferred therapy in patients in whom daytime alertness is particularly important.

  16. Clinical effects of buspirone in social phobia : A double-blind placebo-controlled study

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    denBoer, JA; Westenberg, HGM; Pian, KLH


    Background: The results of open pilot studies suggest that the serotonin-1A (5-HT1A) receptor agonist buspirone might be effective in social phobia. Method: In the present study, the efficacy of buspirone was investigated in patients with social phobia using a 12-week double-blind placebo-controlled

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


    FAYYAZi, Afshin; Salari, Elham; Ali KHAJEH; GAJARPOUR, Abdi


    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...

  18. Effects of oral and intravenous administration of buspirone on food-cocaine choice in socially housed male cynomolgus monkeys. (United States)

    Czoty, Paul W; Nader, Michael A


    Drugs acting at D3 dopamine receptors have been suggested as medications for cocaine dependence. These experiments examined the effects of intravenously and orally administered buspirone, a D2-like receptor antagonist with high affinity for D3 and D4 receptors, on the relative reinforcing strength of cocaine in group-housed male cynomolgus monkeys. Use of socially housed monkeys permitted the assessment of whether social status, known to influence D2-like receptor availability, modulates the behavioral effects of buspirone. Buspirone was administered acutely to monkeys self-administering cocaine under a food-drug choice procedure in which a cocaine self-administration dose-effect curve was determined daily. When administered by either route, buspirone significantly decreased cocaine choice in dominant-ranked monkeys. In subordinate monkeys, however, i.v. buspirone was ineffective on average, and oral buspirone increased choice of lower cocaine doses. The effects of buspirone only differed according to route of administration in subordinate monkeys. Moreover, it is noteworthy that the effects of buspirone were similar to those of the D3 receptor-selective antagonist PG01037 and qualitatively different than those of less selective drugs that act at D2-like or serotonin (5-HT)1A receptors, suggesting a D3 and possibly D4 receptor mechanism of action for buspirone. Taken together, the data support the utility of drugs targeting D3/D4 receptors as potential treatments for cocaine addiction, particularly in combination with enriching environmental manipulations.

  19. The effect of Buspirone on symptoms and quality of life in patients with functional dyspepsia

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    Seyed masood Tabib


    Full Text Available Background: Functional dyspepsia (FD is a heterogeneous disorder of yet unknown etiology which causes a significant reduction in the quality of life. In this study, we compared the effect of buspirone as an agonist of serotonin 5HT1A receptor with amitriptyline and placebo on improving the symptoms and quality of life in patients with functional dyspepsia. Methods: This study was a double-blinded, randomized controlled clinical trial. Using a sequential sampling, patients with the diagnostic criteria of Rome 2 and normal gastrointestinal findings were selected. The subjects were randomly divided into three therapeutic groups receiving amitriptyline, buspirone, and placebo. We used Nepean Dyspepsia Inde (NDI to evaluate the quality of life before and after the treatment. Results: The mean age of subjects was 35.38±12.94 years. Symptom and quality of life scores of the three groups were equal at the beginning but at the end of treatment, these scores were different. Buspirone was more effective than both amitriptyline and placebo in reducing the symptom of early satiety. Buspirone showed a better improvement in quality of life compared to placebo. Both Buspirone and amitriptyline were more effective than placebo in decreasing the symptom of epigastric pain. Conclusion: Our study confirmed the positive effect of buspirone on the quality of life and symptoms (like early satiety and abdominal pain in patients with functional dyspepsia. Since the mechanism of action of buspirone and also the pathophysiology of functional dyspepsia are still unknown, further studies are necessary to clarify every aspect of the disease and therapeutic effects of various treatments on it.

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

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


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

  1. Oral buspirone causes a shift in the dose-response curve between the elevated-plus maze and Vogel conflict tests in Long-Evans rats: relation of brain levels of buspirone and 1-PP to anxiolytic action. (United States)

    Vaidya, A H; Rosenthal, D I; Lang, W; Crooke, J J; Benjamin, D; Ilyin, S E; Reitz, A B


    Most studies concerning the effects of oral buspirone in the rat elevated plus-maze (EPM) test, spontaneous motor activity (SMA) test, and Vogel conflict (VC) test have used Sprague-Dawley or Wistar rats. Although it has been documented that the behavior of Long-Evans rats is more sensitive to detection of anxiolytics when compared to the aforementioned strains, the effects of oral buspirone have not been fully characterized in the Long-Evans strain in the EPM and VC tests. Thus, we studied the effects of orally administered buspirone (0.03-10.0 mg/kg) in the EPM, SMA, and VC (0.3-60.0 mg/kg) tests in Long-Evans rats. In a separate experiment, brain and plasma concentrations of buspirone and 1-(2-pyrimidinyl)-piperazine (1-PP) were determined after oral administration of buspirone (0.3 and 10 mg/kg) to relate the behavioral effects of buspirone with brain and plasma concentrations of buspirone and 1-PP. Our results showed that buspirone exhibited an inverted-U-shaped dose-response curve in both the EPM and the VC tests. In the EPM, buspirone produced anxiolytic activity in a low, narrow dose-range (0.03, 0.1, 0.3 mg/kg, p.o.) with maximum efficacy at 0.3 mg/kg, whereas in the VC test, significant anxiolytic activity was observed in a high, narrow dose-range (10, 30 mg/kg, p.o.) with maximum efficacy occurring at 10 mg/kg. In the SMA test, buspirone (10 mg/kg, p.o.) significantly decreased horizontal activity and vertical movements suggestive of sedation. Also, one hour following oral doses of buspirone (0.3 and 10 mg/kg), both buspirone and 1-PP concentrations were higher in brain when compared with those in plasma. Additionally, the concentrations of 1-PP were always higher in brain and in plasma compared with the concentrations of buspirone. Of particular interest is our finding of the shift in the dose-response curve between the EPM and VC tests. This shift in the dose-response curve is discussed in relation to brain levels of buspirone and 1-PP levels and their

  2. Attenuation of methylphenidate-induced sensitization by co-administration of buspirone. (United States)

    Alam, Nausheen; Najam, Rahila; Naeem, Sadaf


    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 2.0 mg/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 10 mg/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.

  3. The serotonin analogue buspirone increases the function of PBMC from HIV-infected individuals in vitro

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    Afzelius, P; Nielsen, S D; Hofmann, B;


    of the intracellular second messenger cAMP has been demonstrated to cause impaired proliferative capacity of PBMC from HIV-infected individuals in vitro. We have identified a serotonin analogue, buspirone, that inhibits the activity of adenylyl cyclase, the enzyme responsible for regulation of intracellular levels...

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

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


    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.


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    Full Text Available Three simple, accurate, rapid and sensitive methods developed for the determination of buspirone hydrochloride in bulk drug and in its tablets by UV Spectroscopy (Method – A – Water as a Solvent, UV Spectroscopy (Method – B – Methanol as a Solvent, and Colorimetry (Method - C. In Method A buspirone hydrochloride estimated at 236 nm using distilled water as a solvent. The linearity was observed in the concentration range of 5 – 25 μg/ml with correlation co efficient of 0.9866. In Method B methanol used as a solvent. The linearity wasobserved in the concentration range of 10 – 50 μg/ml with correlation co efficient of 0.9905. In Method C buspirone hydrochloride is a colorless compound undergoes oxidation with 0.005M Potassium ermanganate Solution in the presence of 0.5M Sodium Hydroxide gives Pink color. The intensity of color directly proportional to theconcentration of buspirone hydrochloride and its found that intensity of color stable for 20mins and the absorbance was measured at 610 nm with different time intervals with the linearity range and correlation co -efficient of 10 – 50 μg/ml and 0.9924. The result of analysis for all the methods was validated statistically and by ecovery studies.

  6. Nucleus incertus contributes to an anxiogenic effect of buspirone in rats: Involvement of 5-HT1A receptors. (United States)

    Kumar, Jigna Rajesh; Rajkumar, Ramamoorthy; Lee, Liying Corinne; Dawe, Gavin S


    The nucleus incertus (NI), a brainstem structure with diverse anatomical connections, is implicated in anxiety, arousal, hippocampal theta modulation, and stress responses. It expresses a variety of neurotransmitters, neuropeptides and receptors such as 5-HT1A, D2 and CRF1 receptors. We hypothesized that the NI may play a role in the neuropharmacology of buspirone, a clinical anxiolytic which is a 5-HT1A receptor partial agonist and a D2 receptor antagonist. Several preclinical studies have reported a biphasic anxiety-modulating effect of buspirone but the precise mechanism and structures underlying this effect are not well-understood. The present study implicates the NI in the anxiogenic effects of a high dose of buspirone. Systemic buspirone (3 mg/kg) induced anxiogenic effects in elevated plus maze, light-dark box and open field exploration paradigms in rats and strongly activated the NI, as reflected by c-Fos expression. This anxiogenic effect was reproduced by direct infusion of buspirone (5 μg) into the NI, but was abolished in NI-CRF-saporin-lesioned rats, indicating that the NI is present in neural circuits driving anxiogenic behaviour. Pharmacological studies with NAD 299, a selective 5-HT1A antagonist, or quinpirole, a D2/D3 agonist, were conducted to examine the receptor system in the NI involved in this anxiogenic effect. Opposing the 5-HT1A agonism but not the D2 antagonism of buspirone in the NI attenuated the anxiogenic effects of systemic buspirone. In conclusion, 5-HT1A receptors in the NI contribute to the anxiogenic effect of an acute high dose of buspirone in rats and may be functionally relevant to physiological anxiety.

  7. Changes in cognitive symptoms after a buspirone-melatonin combination treatment for Major Depressive Disorder. (United States)

    Targum, Steven D; Wedel, Pamela C; Fava, Maurizio


    Cognitive deficits are often associated with acute depressive episodes and contribute to the functional impairment seen in patients with Major Depressive Disorder (MDD). Many patients sustain residual cognitive deficits after treatment that may be independent of the core MDD disorder. We tracked changes in cognitive deficits relative to antidepressant treatment response using the patient self-rated Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (MGH-CPFQ) during a 6-week, double-blind trial of a combination antidepressant treatment (buspirone 15 mg with melatonin-SR 3 mg) versus buspirone (15 mg) monotherapy versus placebo in MDD patients with acute depressive episodes. The CPFQ includes distinct cognitive and physical functioning dimension subscales. Treatment response was determined using the Inventory of Depressive Symptomatology (IDSc30). Treatment responders improved significantly more on the total CPFQ than non-responders (p symptoms and that some aspects of cognition may be specific targets for treatment within a population of patients with MDD.

  8. Effect of blueberry juice on clearance of buspirone and flurbiprofen in human volunteers (United States)

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


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

  9. Buspirone versus methylphenidate in the treatment of children with attention- deficit/ hyperactivity disorder: randomized double-blind study. (United States)

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


    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

  10. Comparative efficacy of a single oral dose of ondansetron and of buspirone against cisplatin-induced emesis in cancer patients.


    Alfieri, A. B.; Cubeddu, L. X.


    Buspirone, an agonist of the 5-HT1A subtype of serotonin receptors, has shown antiemetic activity in animal models. However, in cancer patients treated with cisplatin, ondansetron, given either i.v. (one 8-mg dose 30 min after cisplatin) or orally (one 16-mg dose at the end of cisplatin infusion) was superior (P < 0.001) to buspirone (60 mg p.o. at the end of cisplatin and 60 mg p.o., 30 min later), in all parameters of antiemetic efficacy. These results are in favour of 5-HT3 receptors, but ...

  11. 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


    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

  12. Buspirone, fexofenadine, and omeprazole: quantification of probe drugs and their metabolites in human plasma. (United States)

    Gor, Parul; Alnouti, Yazen; Reed, Gregory A


    Probe drugs are critical tools for the measurement of drug metabolism and transport activities in human subjects. Often several probe drugs are administered simultaneously in a "cocktail". This cocktail approach requires efficient analytical methods for the simultaneous quantitation of multiple analytes. We have developed and validated a liquid chromatography-tandem mass spectrometry method for the simultaneous determination of three probe drugs and their metabolites in human plasma. The analytes include omeprazole and its metabolites omeprazole sulfone and 5'-hydroxyomeprazole; buspirone and its metabolite 1-[2-pyrimidyl]-piperazine (1PP); and fexofenadine. These analytes and the internal standard lansoprazole were extracted from plasma using protein precipitation with acetonitrile. Gradient reverse-phase chromatography was performed with 7.5mM ammonium bicarbonate and acetonitrile, and the analytes were quantified in positive ion electrospray mode with multiple reaction monitoring. The method was validated to quantify the concentration ranges of 1.0-1000ng/ml for omeprazole, omeprazole sulfone, 5'-hydroxyomeprazole, and fexofenadine; 0.1-100ng/ml for buspirone, and 1.0-100ng/ml for 1PP. These linear ranges span the plasma concentrations for all of the analytes from probe drug studies. The intra-day precision was between 2.1 and 16.1%, and the accuracy ranged from 86 to 115% for all analytes. Inter-day precision and accuracy ranged from 0.3 to 14% and from 90 to 110%, respectively. The lower limits of quantification were 0.1ng/ml for buspirone and 1ng/ml for all other analytes. This method provides a fast, sensitive, and selective analytical tool for quantification of the six analytes in plasma necessary to support the use of this probe drug cocktail in clinical studies.

  13. Tolerance in the anxiolytic profile following repeated administration of diazepam but not buspirone is associated with a decrease in the responsiveness of postsynaptic 5-HT-1A receptors. (United States)

    Khan, Asma; Haleem, D J


    To understand the role of serotonin (5-hydroxytryptamine; 5-HT)-1A receptors in the treatment of anxiety and the development of tolerance to benzodiazepines the present study was designed to monitor the responsiveness of postsynaptic 5-HT-1A receptors following repeated administration of diazepam and buspirone. Results show that tolerance in the anxiolytic profile is produced following repeated administration (2 weeks) of diazepam (2 mg/kg) but not buspirone (0.5 mg/kg). The behavioral effects of 8-OH-DPAT at a dose of 0.25 mg/kg were monitored 3 days after repeated administration of saline or buspirone or diazepam. The results show that 8-OH-DPAT elicited forepaw treading was smaller in repeated diazepam but not repeated buspirone injected rats, while hyperlocomotive effects of 8-OH-DPAT were smaller in both repeated buspirone and repeated diazepam injected rats. The results suggest that postsynaptic 5-HT-1A receptor-dependent responses were attenuated following long-term administration of diazepam but not buspirone. Role of 5-HT-1A receptors in the development of tolerance to the anxiolytic effects of diazepam but not buspirone is discussed.

  14. Buspirone, chlordiazepoxide and diazepam effects in a zebrafish model of anxiety. (United States)

    Bencan, Zachary; Sledge, Damiyon; Levin, Edward D


    Zebrafish are becoming more widely used to study neurobehavioral pharmacology. We have developed a method to assess novel environment diving behavior of zebrafish as a model of stress response and anxiolytic drug effects. In a novel tank, zebrafish dwell in the bottom of the tank initially and then increase their swimming exploration to higher levels over time. We previously found that nicotine, which has anxiolytic effects in rodents and humans, significantly lessens the novel tank diving response in zebrafish. The specificity of the diving effect was validated with a novel vs. non-novel test tank. The novel tank diving response of zebrafish was tested when given three anxiolytic drugs from two different chemical and pharmacological classes: buspirone, chlordiazepoxide and diazepam. When the test tank was novel the diving response was clearly seen whereas it was significantly reduced when the test tank was not novel. Buspirone, a serotonergic (5HT(1A) receptor agonist) anxiolytic drug with some D(2) dopaminergic effect, had a pronounced anxiolytic-like effect in the zebrafish diving model at doses that did not have sedative effects. In contrast, chlordiazepoxide, a benzodiazepine anxiolytic drug, which is an effective agonist at GABA-A receptors, did not produce signs of anxiolysis in zebrafish over a broad dose range up to those that caused sedation. Diazepam another benzodiazepine anxiolytic drug did produce an anxiolytic effect at doses that did not cause sedation. The zebrafish novel tank diving task can be useful in discriminating anxiolytic drugs of several classes (serotonergic, benzodiazepines and nicotinic).

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

    Directory of Open Access Journals (Sweden)

    Afshin FAYYAZI


    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

  16. Decision time and perseveration of adolescent rats in the T-maze are affected differentially by buspirone and independent of 5-HT-1A expression. (United States)

    Rhoads, Dennis E; Grimes, Nicole; Kaushal, Sunaina; Mallari, Janine; Orlando, Krystal


    Disruption of spontaneous alternation behavior (SAB) by the serotonin 1A (5-HT-1A) receptor agonist, 8-hydroxy-dipropylaminotetraline (8-OH-DPAT), results in repetitive behaviors that have been used to model the perseveration and indecisiveness of human obsessive-compulsive disorder (OCD). In the present study, we compared the effects of buspirone to those of 8-OH-DPAT in two strains of adolescent rats and analyzed repetitive choices of arms of the maze and prolonged apparent decision time due to induction of vicarious trial and error (VTE) behavior. In adolescent Sprague-Dawley (SD) rats, 8-OH-DPAT induced repetitive choices of arms of the maze (perseveration) and increased the apparent decision time. Buspirone induced VTE behavior and increased apparent decision time without perseveration. This distinct effect of buspirone was seen in SD adolescents but not in Long-Evans (LE) adolescents which appeared to be insensitive to buspirone. Lack of responsiveness to buspirone was dependent on the developmental stage because buspirone induced VTE behavior and prolonged decision time in LE adults. Western blotting of brain 5-HT-1A receptors showed expression of receptor protein in adolescent LE brain was comparable to that of adolescent SD and adult LE. The 5-HT-1A antagonist WAY 100365 blocked the effect 8-OH-DPAT on repetitive choice of arms but not the effect of buspirone on VTE behavior. We conclude that the adolescent LE rat has normal levels of 5-HT-1A receptor and that the effect of buspirone on VTE behavior is not mediated by the 5-HT-1A receptor. The LE strain may provide a useful system for further study of the adolescent brain and potential genetic differences in induction of repetitive behaviors.

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

    DEFF Research Database (Denmark)

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


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

  18. Evaluation of buspirone for relapse-prevention in adults with cocaine dependence: an efficacy trial conducted in the real world. (United States)

    Winhusen, Theresa; Brady, Kathleen T; Stitzer, Maxine; Woody, George; Lindblad, Robert; Kropp, Frankie; Brigham, Gregory; Liu, David; Sparenborg, Steven; Sharma, Gaurav; Vanveldhuisen, Paul; Adinoff, Bryon; Somoza, Eugene


    Cocaine dependence is a significant public health problem for which there are currently no FDA-approved medications. Hence, identifying candidate compounds and employing an efficient evaluation process is crucial. This paper describes key design decisions made for a National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) study that uses a novel two-stage process to evaluate buspirone (60 mg/day) for cocaine-relapse prevention. The study includes pilot (N=60) and full-scale (estimated N=264) trials. Both trials will be randomized, double-blind, and placebo-controlled and both will enroll treatment-seeking cocaine-dependent participants engaged in inpatient/residential treatment and scheduled for outpatient treatment post-discharge. All participants will receive contingency management in which incentives are given for medication adherence as evaluated by the Medication Events Monitoring System (MEMS). The primary outcome measure is maximum days of continuous cocaine abstinence, as assessed by twice-weekly urine drug screens (UDS) and self-report, during the 15-week outpatient treatment phase. Drug-abuse outcomes include cocaine use as assessed by UDS and self-report of cocaine use, other substance use as assessed by UDS and self-report of substance use (i.e., alcohol and/or illicit drugs), cocaine bingeing, HIV risk behavior, quality of life, functioning, and substance abuse treatment attendance. Unique aspects of the study include conducting an efficacy trial in community treatment programs, a two-stage process to efficiently evaluate buspirone, and an evaluation of mediators by which buspirone might exert a beneficial effect on relapse prevention.

  19. Long-Term Effects of Chronic Buspirone during Adolescence Reduce the Adverse Influences of Neonatal Inflammatory Pain and Stress on Adaptive Behavior in Adult Male Rats. (United States)

    Butkevich, Irina P; Mikhailenko, Viktor A; Vershinina, Elena A; Aloisi, Anna M; Barr, Gordon A


    Neonatal pain and stress induce long-term changes in pain sensitivity and behavior. Previously we found alterations in pain sensitivity in adolescent rats exposed to early-life adverse events. We tested whether these alterations have long-lasting effects and if those effects can be improved by the 5-hydroxytryptamine 1A (5-HT1A) receptor agonist buspirone injected chronically during the adolescent period. This study investigates: (1) effects of inflammatory pain (the injection of formalin into the pad of a hind paw) or stress (short maternal deprivation-isolation, MI), or their combination in 1-2-day-old rats on the adult basal pain, formalin-induced pain, anxiety and depression; (2) effects of adolescent buspirone in adult rats that experienced similar early-life insults. Changes in nociceptive thresholds were evaluated using the hot plate (HP) and formalin tests; levels of anxiety and depression were assessed with the elevated plus maze and forced swim tests respectively. Both neonatal painful and stressful treatments induced long-term alterations in the forced swim test. Other changes in adult behavioral responses were dependent on the type of neonatal treatment. There was a notable lack of long-term effects of the combination of early inflammatory pain and stress of MI on the pain responses, anxiety levels or on the effects of adolescent buspirone. This study provides the first evidence that chronic injection of buspirone in adolescent rats alters antinociceptive and anxiolytic effects limited to adult rats that showed behavioral alterations induced by early-life adverse treatments. These data highlight the role of 5-HT1A receptors in long-term effects of neonatal inflammatory pain and stress of short MI on adaptive behavior and possibility of correction of the pain and psychoemotional behavior that were altered by adverse pain/stress intervention using buspirone during critical adolescent period.

  20. Tardive Dyskinesia Revisited-A Clinical Management Priority Perspective: A Voyage into High Dose Buspirone Part B

    Directory of Open Access Journals (Sweden)

    Vernon M Neppe


    Full Text Available We discuss several major related and integrated issues in this two-part series of papers on tardive dyskinesia (TD. In this, the second paper, Part B, the management and mechanisms are emphasized; in Part A the diagnosis and assessment of tardive dyskinesia was discussed. In this Part B series of articles we examine several special important priorities in this condition associated with sometimes permanent involuntary abnormal movements associated with the neuroleptic drugs. We particularly examine the management of this enormously important condition. After the diagnosis and assessment of TD, comes the clinical approach to management and the options and theories behind that approach. There remain no approved medications for the management of tardive dyskinesia. Therefore, all treatments are “out of labeling”. The purpose of this paper is to shed light on high dose buspirone treatment, originally described by the author in 1989 [1], and which after more than a quarter century requires re-evaluation as it still appears, in the author’s opinion, to be the logical and most appropriate management for TD. A major issue focuses, on the updated experience of more than a quarter century with generally almost completely positive effects of high-dose buspirone (HDB treatment of tardive dyskinesia (TD and the next issue provides an important, major theoretical demonstration of the mechanism of tardive dyskinesia. The dopamine 2 or 2-3 supersensitivity hypothesis as a cause of TD is strongly supported by HDB. In Part B, the issue of choice of medication for psychosis and related medical conditions becomes pertinent. The choices relate to the newer second generation atypical neuroleptics (SGAs compared with the older typical, first generation neuroleptics (FGAs. The generally more expensive SGA drugs have become far the most used anti-psychotic agents in wealthy countries such as the United States, because of their efficacy and ostensible safety

  1. Effect of the 5-HT(1A) partial agonist buspirone on regional brain electrical activity in man: a functional neuroimaging study using low-resolution electromagnetic tomography (LORETA). (United States)

    Anderer, P; Saletu, B; Pascual-Marqui, R D


    In a double-blind, placebo-controlled study, the effects of 20 mg buspirone - a 5-HT(1A) partial agonist - on regional electrical generators within the human brain were investigated utilizing three-dimensional EEG tomography. Nineteen-channel vigilance-controlled EEG recordings were carried out in 20 healthy subjects before and 1, 2, 4, 6 and 8 h after drug intake. Low-resolution electromagnetic tomography (LORETA; Key Institute for Brain-Mind Research, software: was computed from spectrally analyzed EEG data, and differences between drug- and placebo-induced changes were displayed as statistical parametric maps. Data were registered to the Talairach-Tournoux human brain atlas available as a digitized MRI (McConnell Brain Imaging Centre: At the pharmacodynamic peak (1st hour), buspirone increased theta and decreased fast alpha and beta sources. Areas of theta increase were mainly the left temporo-occipito-parietal and left prefrontal cortices, which is consistent with PET studies on buspirone-induced decreases in regional cerebral blood flow and fenfluramine-induced serotonin activation demonstrated by changes in regional cerebral glucose metabolism. In later hours (8th hour) with lower buspirone plasma levels, delta, theta, slow alpha and fast beta decreased, predominantly in the prefrontal and anterior limbic lobe. Whereas the results of the 1st hour speak for a slight CNS sedation (more in the sense of relaxation), those obtained in the 8th hour indicate activation. Thus, LORETA may provide useful and direct information on drug-induced changes in central nervous system function in man.

  2. 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


    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.

  3. Enhanced bioavailability of buspirone from reservoir-based transdermal therapeutic system, optimization of formulation employing Box-Behnken statistical design. (United States)

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


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

  4. 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


    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.

  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, Jesper; Benfield, T; Axen, T E;


    . Blood samples were drawn prior to treatment, after 1 week, 1 month, 3 months, and 6 months, and as a follow-up sample 1 month after completion of study. RESULTS: A significant decrease in CD8+ T-cell counts (p =.02) and an increase in CD4/CD8 ratio (p =.0003) in buspirone-treated patients compared......PURPOSE: Previous studies have shown that agents modulating the cAMP/PKA pathway have a beneficial effect on immune reconstitution in HIV-infected individuals. Here we evaluate the effect of buspirone on immune function as measured by CD4 and CD8 T-cell counts, CD4/CD8 T-cell ratio, HIV viral load......, 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 study...

  6. Modulatory effect of the 5-HT1A agonist buspirone and the mixed non-hallucinogenic 5-HT1A/2A agonist ergotamine on psilocybin-induced psychedelic experience. (United States)

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


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

  7. Combination of capillary micellar liquid chromatography with on-chip microfluidic chemiluminescence detection for direct analysis of buspirone in human plasma. (United States)

    Al Lawati, Haider A J; Kadavilpparampu, Afsal Mohammed; Suliman, FakhrEldin O


    Microfluidic based chemiluminescence (CL) detector having novel channel design for enhanced mixing has been developed and investigated in terms of its applicability with micellar mode of liquid chromatography (MLC). The newly developed detector was found to be highly sensitive and an alternative detection technique to combine with capillary MLC. This combination was successfully employed for direct detection of a model analyte using Ru(III)-peroxydisulphate CL system. The selected analyte, buspirone hydrochloride (BUS), was detected selectively at therapeutic concentration levels in human plasma without any sample pretreatment. By incorporating eight flow split units within the spiral channel of microfluidic chip, an enhancement of 140% in CL emission was observed. We also evaluated the effect of non- ionic surfactant, Brij-35, which used as mobile phase modifier in MLC, on CL emission. The CL signal was improved by 52% compared to aqueous-organic mobile phase combinations. Various parameters influencing the micellar chromatographic performance and the CL emission were optimized. This allowed highly sensitive analysis of BUS with limit of detection (LOD) of 0.27 ng mL(-1) (3σ/s) and limit of quantification (LOQ) of 0.89 ng mL(-1) (10σ/s). The analyte recovery from human plasma at three different concentration level ranges from 88% to 96% (RSD 1.9-5.3%). The direct analysis of BUS in human plasma was achieved within 6 min. Therefore, combining microfluidic CL detection with micellar mode of separation is an efficient, cost-effective and highly sensitive technique that can utilize MLC in its full capacity for various bioanalytical procedures.

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

    Institute of Scientific and Technical Information of China (English)

    罗世芳; 曾德志; 樊学文; 罗建武


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

  9. A control study of sertraline combined with buspirone in de-pression with sexual dysfunction%舍曲林联合丁螺环酮治疗抑郁症伴性功能障碍对照研究

    Institute of Scientific and Technical Information of China (English)

    徐清河; 许锦泉; 李冬梅


    Objective To explore the efficacy of sertraline combined with buspirone in depression with sex-ual dysfunction .Methods A total of 100 depression patients with sexual dysfunction were randomly as-signed to two groups of 50 ones each ,both groups took orally sertraline ,observation group was plus bus-pirone for 8 weeks . Depression status was assessed with the Hamilton Rating Scale for Depression (HRSD) and Self-rating Depression Scale (SDS) ,marital quality with the Olson Marital Quality Question-naire (ENRICH) ,and sexual satisfaction with the Sexual Satisfaction Scale (SSS) .Results After treat-ment the HRSD and SDS scores of both groups lowered more significantly compared with pre-treatment (P<0 .01) ,so did those in observation than in control group (P< 0 .01);the ENRICH scores of both groups heightened more significantly (P<0 .01) ,so did those in observation than in control group (P<0 .01);sexual satisfaction was significantly higher in observation than in control group (χ2 = 7 .48 , P<0 .01) .Conclusion Sertraline combined with buspirone has an evident effect in depression with sexual dys-function ,can notably improve sexual satisfaction and marital quality compared with single sertraline .%目的:探讨舍曲林联合丁螺环酮治疗抑郁症伴性功能障患者的临床疗效。方法将100例抑郁症伴性功能障碍患者随机分为两组,每组50例,两组均口服舍曲林治疗,观察组联合丁螺环酮合治疗,观察8周。采用汉密顿抑郁量表、抑郁自评量表评定抑郁状况,Olson婚姻质量问卷评定婚姻质量,性生活满意度量表评定性生活满意度。结果治疗后两组汉密顿抑郁量表、抑郁自评量表评分均较治疗前显著下降(P<0.01),观察组较对照组下降更显著(P<0.01);两组Olson婚姻质量问卷评分均较治疗前显著升高(P<0.01),观察组较对照组升高更显著(P<0.01);观察组性生活总满意率

  10. Synergistic function study of risperidone combined buspirone in the treatment of homeless patients with mental disorders%利培酮合并丁螺环酮治疗流浪精神障碍患者的效果分析

    Institute of Scientific and Technical Information of China (English)



    Objective To investigate the synergistic function and safety of risperidone combined buspirone in the treatment of homeless patients with mental disorders.Methods 96 homeless patients with mental disorders were divided into the control group and the observation group according to the random number table,48 cases in each group.The control group was given ris-peridone and the observation group was given buspirone based on the control group.After 8 weeks,the clinical efficacy was com-pared between two groups by the reduction rate of PANSS scale and symptom group score of PANSS,and the side effects of the two groups were also evaluated.Results Total efficiencies of the two groups had significant difference (P 0.05).Conclusion Risperidone combined buspirone treatment for homeless patients with mental disorders have syn-ergistic function and better security,and it should be widely applied.%目的:探讨利培酮合并丁螺环酮对流浪精神障碍患者治疗的增效作用及安全性。方法选取96例流浪精神障碍患者,根据数字法随机分为对照组和研究组,每组48例。对照组给予利培酮治疗,研究组在对照组基础上合并丁螺环酮,8周后根据 PANSS 量表减分率及 PANSS 量表症状群评分比较两组临床疗效,同时观察两组不良反应发生情况。结果研究组总有效率明显高于对照组,差异统计学意义(P <0.05)。两组治疗前后 PANSS 症状群评分比较,差异有统计学意义(P <0.05),研究组 PANSS 症状群评分下降更明显(P <0.05),两组不良反应发生率比较,差异无统计学意义(P >0.05)。结论利培酮合并丁螺环酮对流浪精神障碍患者治疗有明显的增效作用,且安全性较好,值得推广应用。


    Institute of Scientific and Technical Information of China (English)

    杨培润; 钱刚; 罗素元; 吴明松


    目的:探讨丁螺环酮治疗吗啡依赖戒断焦虑的细胞和分子机制.方法:66只雄性SD大鼠随机分为生理盐水对照组(对照组)、吗啡戒断焦虑组(模型组)、丁螺环酮治疗组(治疗组).吗啡剂量递增皮下注射10 d自然戒断,于戒断1-3 d丁螺环酮灌胃治疗行高架十字迷宫实验后,取海马CA3区和杏仁核组织,用电镜体视学方法定量检测其各组突触的数密度(Nv)、面密度(Sv)、突触连接带平均面积(S),Western-blot技术检测其CaMKII的含量和磷酸化水平.结果:与模型组比较,治疗组大鼠进入开放臂的次数和时间明显增加(P<0.01或P<0.05);海马CA3区和杏仁核突触的Nv和Sv显著降低、S增加(P<0.01或P<0.05),CaMK II蛋白含量和β亚基磷酸化水平显著下调(P<0.01或P<0.05).结论:逆转吗啡戒断焦虑大鼠海马、杏仁核突触结构的可塑性和CaMKⅡ分子的变化可能是丁螺环酮缓解吗啡戒断焦虑的重要细胞和分子机制.%Objective: To explore the cellular and molecular mechanism of buspirone on anxiety in morphine withdrawal rats . Methods: The 66 male SD rats were randomly divided into three groups: the saline (control) , the morphine( model) , and the buspirone (treatment) . Gradually increasing dosage of morphine with hypodermic injection is applied to validate the morphine dependence for 10 days before the elevated plus maze . Thus, the model rats are subjected to buspirone treatment for 1 -3 d. The tissue of hippocampal region of CA3 and amygdala was harvested to test the scores of Nv(numerical density) , Sv(surface density; and S(surface) with electron microscopy stereology. Total and phosphorylated levels of CaMKII are detected by Western blotting. Results: Compared with the model group, the rats treated with buspirone had higher frequency and longer time in open arm ( P < 0. 01 orP<0.05), and the lower values of Nv and Sv and higher score of S were observed in CA3 region of hippocampus and amygdale (P

  12. Observation of Clinical Effects of Buspirone Combined with Antipsychotic Drugs in the Treatment of Schizophrenia with Psychopathology and Drug-induced Anxiety%丁螺环酮与抗精神病药物联用治疗精神分裂症患者病理性或药源性焦虑的疗效观察

    Institute of Scientific and Technical Information of China (English)

    周慧民; 韦德会


    目的:观察丁螺环酮与抗精神病药物联用治疗精神分裂症患者病理性或药源性焦虑的疗效.方法:将2008年2月-2012年2月在我院就诊的精神分裂症患者240例,按疾病类型的不同随机分为单用抗精神病药物组(A组)和抗精神病药物联用丁螺环酮组(B组).A组患者用药包括氯丙嗪、氯氮平、阿立哌唑、利培酮,B组患者为氯丙嗪、氯氮平、阿立哌唑、利培酮分别与丁螺环酮联用.然后进行各药物的单用和联用两两配对观察,共计4对、8小组,每小组纳入病例30例.采用汉密尔顿焦虑量表(HAMA)和阳性与阴性症状量表(PANSS)于入组前和入组后1、2、4、8、12周末各评定1次,对焦虑症状缓解程度及治疗效果进行比较.结果:各个时间点的HAMA和PANSS减分B组均快于A组(P<0.05或P<0.01),B组的抗精神病药物用量也少于A组(P<0.01),但总有效率两组比较差异无统计学意义(P>0.05).所有患者用药过程中均未见不良反应发生.结论:抗精神病药物与丁螺环酮联合使用可快速缓解精神病患者的精神症状,且可减少抗精神病药物的用量,安全性较好.%OBJECTIVE: To investigate therapeutic efficacies of buspirone combined with antipsychotic drugs in the treatment of schizophrenia with psychopathology and drug-induced anxiety. METHODS: 240 patients with schizophrenia were randomly divided into antipsychotic drugs alone group (group A) and antipsychotic drugs combined with buspirone (group B) in our hospital during Feb. 2008 -Feb. 2012. Group A received chlorpromazine, clozapine, aripiprazole and risperidone, and group B was given buspirone combined with clozapine, aripiprazole or risperidone. Therapy of single drug and two-drug were observed. A total of 4 pairs and 8 groups were formulated with 30 cases in each group. Therapeutic efficacy was evaluated with HAMA and PANSS before and 1, 2, 4, 8, 12 weeks of therapy. RESULTS: The reduction rates of HAMA and

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

    Institute of Scientific and Technical Information of China (English)

    韩跃平; 石顺治


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

  14. 丁螺环酮与艾司西酞普兰联合治疗脑卒中后中重度抑郁的临床观察%Clinical observation of post-stroke depression by Buspirone combined with Escitalopram

    Institute of Scientific and Technical Information of China (English)

    原富强; 马振武; 于洪岩


    Objective: To compare the effect and safety of Buspirone combined with Escitalopram and Escitalopram used singly in the treatment of post-stroke depression. Methods: Totally the 60 post-stroke depression patients were randomized into control group (n=30), treated with Escitalopram, and study group (n=30), treated by Buspirone combined with Escitalopram. The observation lasted 8 weeks. The therapeutic effect and safety were evaluated by the positive and negative syndrome scale of HAMD (24 items), and treatment emergent symptom scale of TESS. Results: Total effective rate of the study group was 93.3%(28/30) and with the control group 63.3% (23/30), there was a significant difference (x2=8.91 ,P=0.031, P<0.05), and according to HAMD total scores assessment there was a significant difference hetween two groups (P<0.05) after the treatment in different weekend. The difference of TESS scores between two groups was not significant.Conclusion: Buspirone combined with Escitalopram is effective and safe in the treatment of post-stroke depression.%目的:比较丁螺环酮与艾司西酞普兰联用治疗脑卒中后中重度抑郁与单用艾司西酞普兰治疗的疗效及安全性.方法:选择脑卒中后中重度抑郁患者60例,随机分为两组,各30例.研究组采用丁螺环酮与艾司西酞普兰联合治疗,对照组单用艾司西酞普兰治疗,观察疗程均为8周,定期对患者采用HAMD(24项)抑郁量表与TESS副反应量表进行疗效评估.结果:研究组临床疗效总有效率为93.3%(28/30),显著优于对照组的63.3%(19/30)(x2=8.91,P=0.031,P<0.05).两组治疗后HAMD评定,治疗第1周开始较治疗前有统计学意义,且一直持续至观察第8周.研究组与对照组比较亦有统计学意义(P<0.05).两组治疗期间副反应无统计学意义.结论:艾司西酞普兰联用丁螺环酮治疗脑卒中后抑郁较单用艾司西酞普兰治疗疗效显著,安全性高.

  15. 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


    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

  16. 丁螺环酮对女性抑郁症患者抑郁症状及性功能的影响%study on the effect of buspirone on depressive symptoms and sexual function in female patients with depression

    Institute of Scientific and Technical Information of China (English)



    Objective To explore the effect of buspirone on depressive symptoms and sexual function in female patients with depression. Methods A total of 60 female patients with depression and sexual dysfunction during August 2014 to August 2015 were divided into observation group and control group by using SAS software to produce sequence number,30 cases in each group,patients in control group were continuously taken with antidepressant treatment,patients in observation group were given with buspirone on the basis of the treatment in control group,and the treat-ment in these two groups had been continuously carried out for 8 weeks. The Hamilton Depression Rating Scale(HAMD)and Zung's depression self rating scale(SDS)were used to survey the depressive symptoms of patients before and after treatment,the questionnaire survey for female sexual function index(FSFI)was used for survey of sexual function,Olson marital quality questionnaire was used for marital quality,comprehensive assess-ment of life quality questionnaire(GQOL -74)was applied for the survey of life quality. Results After treatment,HAMD scores and SDS scores in patients of observation group were lower than those of patients in control group,and the difference was statistically significant( P <0. 05). The de-grees of sexual desire,vaginal lubrication,orgasm and sexual satisfaction in patients of observation group after treatment were higher than those of pa-tients in control group,and the difference was statistically significant( P <0. 05). Marital quality and life quality scores after treatment in patients of observation group were higher than those of patients in control group,and the difference was statistically significant( P <0. 05). Conclusion Buspirone can improve the depression symptoms,and it also can improve the sexual dysfunction,marital quality and life quality of female patients with depression.%目的 探讨丁螺环酮对女性抑郁症患者抑郁症状及性功能的影响.方法 选取2014年8

  17. Observation on the inc reasing effect of different doses of buspirone in combination with paroxetine treating depression%不同剂量丁螺环酮联合帕罗西汀治疗抑郁症增效作用的观察

    Institute of Scientific and Technical Information of China (English)

    朱毅平; 耿松; 郭萍; 钱敏才; 沈鑫华; 杨胜良


    西汀联合丁螺环酮40 mg/d组,对抑郁症伴随的焦虑症状疗效优于丁螺环酮20 mg/d组,也优于单一使用帕罗西汀组。研究A组治愈率61.90%、研究B组治愈率60.24%、对照组治愈率37.78%,研究组治愈率高于对照组,有统计学意义( R=0.48,P<0.05),三组患者常见的不良反应是头痛(头晕)、恶心(厌食)、出汗、便秘,发生率无统计学意义(χ2=0.52, P>0.05)。结论丁螺环酮联合帕罗西汀治疗抑郁症可以有效地改善抑郁症状,同时也能有效地改善抑郁症患者伴随的焦虑症状,提高抑郁症患者的临床治愈率及有效率。丁螺环酮联合帕罗西汀不良反应轻微,治疗期间定期复查血常规是必要的。%Objective To research the effect and safety of different doses of buspirone in combination with paroxitinte on patients with depression .Methods This research was prospective and open . The whole round of research took 8 weeks.Patients conformed to the diagnosis standard of CCMD-3 were selected in the survey .They were randomly divided into treatment group A (84 patients,treated with buspirone in combination with paroxitinte 40 mg/d), treatment group B (83 patients, treated with buspirone in combination with paroxitinte 20 mg/d)and control group(45 patients,treated only with paroxetine).Before the research,the evaluations were taken Hamilton depression scale ( HAMD) and Hamilton anxiety scale (HAMA).At the end of the 1st,2nd,4th and 8th week,the evaluations were taken again with HAMD ,HAMA and treatment emergent symptom scale (TESS).Electrocardiogram,blood routine,urine routine,liver function and kidney routine were checked both before the research and at the end of the 8th week.The data were managed with the software of SPSS 13.0 and compared with each other and counting data were examined with One-Way ANOVA,χ2 test.The effective rate was analyzed with Ridit .Results For the patients taking paroxetine ,and zolpidem the dose

  18. Buspirone, Chlordiazepoxide and Diazepam Effects in a Zebrafish Model of Anxiety



    Zebrafish are becoming more widely used to study neurobehavioral pharmacology. We have developed a method to assess novel environment diving behavior of zebrafish as a model of stress response and anxiolytic drug effects. In a novel tank, zebrafish dwell in the bottom of the tank initially and then increase their swimming exploration to higher levels as the session progresses. We previously found that nicotine, which has anxiolytic effects in rodents and humans, significantly lessens the nove...

  19. Buspirone, fexofenadine, and omeprazole: Quantification of probe drugs and their metabolites in human plasma


    Gor, Parul; Alnouti, Yazen; Reed, Gregory A.


    Probe drugs are critical tools for the measurement of drug metabolism and transport activities in human subjects. Often several probe drugs are administered simultaneously in a —cocktail . This cocktail approach requires efficient analytical methods for the simultaneous quantitation of multiple analytes. We have developed and validated a liquid chromatography-tandem mass spectrometry method for the simultaneous determination of three probe drugs and their metabolites in human plasma. The anal...

  20. 13C cpmas nmr and molecular modeling in the studies of new analogues of buspirone. (United States)

    Pisklak, Maciej; Perliński, Mirosław; Kossakowski, Jerzy; Wawer, Iwona


    Three derivatives of 1,4 dichloro-dibenzo[e,h]-bicyclo[2.2.3]octane-2,3-dicarboximide were examined by 13C CPMAS NMR. Low energy conformations were found by a semi-empirical AM1 approach, NMR shielding constants were calculated using the GIAO RHF method.

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

    Institute of Scientific and Technical Information of China (English)

    王小平; 徐莉萍; 李凌江; 孙业华; 刘铁桥; 蒋少艾; 张向晖


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

  2. Drug: D00702 [KEGG MEDICUS

    Lifescience Database Archive (English)

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

  3. Drug: D07593 [KEGG MEDICUS

    Lifescience Database Archive (English)

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

  4. Identification of Splice Variants as Molecular Markers in Parkinson’s Disease (United States)


    compazine, beta blockers ; e. Drugs with significant muscarinic receptor antagonist activity: Cogentin, Akineton, Artane, Ditropan, Detrol, Elavil...f. Drugs known to improve dyskinesias: amantadine, dextromethorphan, beta - blockers , fluoxitene, clozapine, quetiapine, olanzapine, buspirone, other

  5. Drug interactions in controlled clinical trials. (United States)

    Gershon, S


    As much information as possible should be obtained in clinical trials to assess possible interactions between test drugs and concomitant medications prescribed for other medical indications. Side effect profiles were compared in patients taking buspirone, mean = 20 mg/day; diazepam, 20 mg/day; clorazepate, 23 mg/day; and placebo, with or without concomitant medications. Approximately 1,000 anxious patients were included in the analysis; 700 received buspirone. The use of a variety of common medications did not affect the side effect profile in the buspirone, clorazepate, and placebo groups, but did increase the incidence of side effects in the diazepam group. The increased incidence of sedation noted with diazepam and clorazepate, however, was not due to concomitant medication.

  6. Oxytocin and Social Support as Synergistic Inhibitors of Aversive Fear Conditioning and Fear-Potentiated Startle in Male Rats (United States)


    Davis M (1997). Evidence of contextual fear after lesions of the hippocampus : a disruption of freezing but not fear-potentiated startle. f Neurosci 17...monkeys by morphine , diazepam, and buspirone. Bioi Psychiatry 61: 389-395.     Appendix  2:     2009 MHRF Oral  presentation  #S3

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

    NARCIS (Netherlands)

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


    The feasibility of titanium dioxide (TiO2) photocatalysis, electrochemically assisted Fenton reaction (EC-Fenton) and direct electrochemical oxidation (EC) for simulation of phase I metabolism of drugs was studied by comparing the reaction products of buspirone, promazine, testosterone and 7-ethoxyc

  8. Placebo Medication Use for Behavior Management in an Adult with Autism (United States)

    Kroeger, K. A.; Brown, Jennifer


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

  9. [Effect of aconiti laterlis radix compatibility of glycyrrhizae radix on CYP3A4 in vivo]. (United States)

    Zhang, Guangping; Zhu, Lijun; Zhou, Juan; Tang, Lan; Liu, Zhongqiu; Ye, Zuguang


    The primary objective was to develope a UPLC method for determine the concentration of buspirone hydroxychloride in plasma and to evaluate the effects of Aconiti Laterlis Radix and Aconiti Laterlis Radix compatibility of Glycyrrhizae Radix on CYP3A4 in vivo. ACQUITY UPLC BEH C18 column (2.1 mm x 10 mm, 1.7 microm) was used for the gradient elution with a 2.0 mmol x L(-1) ammonium acetate (pH 7.4, A)-acetonitrile (B) solution, 0-2.2 min, 10% - 60% B, 2.2-2.5 min, 60% B, 2.5-3.0 min, 60%-75% B, 3.0-3.5 min, 75% B, 3.5-4.0 min, 75%-10% B, at the flow rate of 0.3 mL x min(-1) at room temperature. The UV wavelenght was detected at 243 nm. The linear calibration curve ranged between 0.078 125-20.0 microg (r = 0.9975). The average recovery (n = 6) of buspirone hydroxychloride was 85.62% (RSD 6.8%). The results showed that this method has good specificity and repeatability, and which can be used for the determination of buspirone hydrochlorid in serum. In animial studies, single dose Aconiti Laterlis Radix extract treatment (0.5 g x kg(-1)) decreased buspirone hydroxychloride AUC(0-2 h) (52.8%, P = 0.020), increased CL/F (122%, P = 0.045). Compared to the saline treatment group, Aconiti Laterlis Radix compatibility of Glycyrrhizae Radix extract treatment has no effect on CYP3A4 in rat. The results indicated that Aconiti Laterlis Radix extract induced CYP3A4 while Aconiti Laterlis Radix compatibility of Glycyrrhizae Radix extract had no effect on CYP3A4 in vivo. Aconiti Laterlis Radix had been detoxified when be used as compatibility of Glycyrrhizae Radix.

  10. Daidzin and daidzein suppress free-choice ethanol intake by Syrian golden hamsters.


    Keung, W M; Vallee, B L


    Syrian Golden hamsters prefer and consume large and remarkably constant amounts of ethanol in a simple two-bottle free-choice regimen. Ethanol intake is significantly suppressed by zimelidine, bromocriptine, buspirone, and lithium carbonate, pharmacological agents that have been shown to be beneficial in controlling ethanol intake in alcohol-dependent humans. These results suggest that this ethanol-drinking animal model has high "predictive validity" and can be used effectively in the search ...

  11. PRX-00023, a selective serotonin 1A receptor agonist, reduces ultrasonic vocalizations in infant rats bred for high infantile anxiety. (United States)

    Brunelli, Susan A; Aviles, Jessica A; Gannon, Kimberly S; Branscomb, Aron; Shacham, Sharon


    To address the development of early anxiety disorders across the lifespan, the High USV line of rats was bred based on rates of infant ultrasonic vocalization in the 40-50 kHz range of predominant frequencies (USV) to maternal separation at postnatal day (P) 10. In this study, rates of USV in High line infants (pups: Postnatal Day 11+/-1) were compared to those of randomly-bred controls in response to EPIX compound PRX-00023, a unique serotonin (5-HT) agonist, acting exclusively at the 5-HT1A receptor, or buspirone, a nonspecific 5HT1A agonist. After testing, pups were examined for sedation and other drug-related effects. The results indicated that all doses of buspirone reduced USV rates in isolation, consistent with other reports. PRX-00023 significantly reduced USV rates at the lowest doses (0.01-0.05 mg/kg). None of the PRX-00023 doses produced sedation, whereas all but the lowest dose of buspirone (0.1 mg/kg) produced sedation effects. The results suggest that this compound alleviates infantile anxiety-like behavior with great specificity in rats bred for high anxiety/depressive phenotypes by selectively targeting 5-HT1A receptors, possibly by both pre- and post-synaptic mechanisms.

  12. Isobolographic analysis of the sedative interaction between six central nervous system depressant drugs and Valeriana edulis hydroalcoholic extract in mice. (United States)

    Ugalde, Martha; Reza, Victoria; González-Trujano, Ma Eva; Avula, Bharathi; Khan, Ikhlas A; Navarrete, Andrés


    It has been declared frequently that valerian may potentiate the effect of other central nervous system (CNS) depressant drugs, however there has been a lack of experimental data. We have evaluated the profile of the interactions between the ethanol extract of Valeriana edulis spp procera and six CNS depressant drugs using an exploratory model to test the sedative effect in mice. All the compounds tested showed a dose-dependent sedative effect with the following ED50 values: valerian 181.62, diazepam 1.21, ethanol 1938, pentobarbital 11.86, buspirone 1.04, haloperidol 0.41 and diphenhydramine 17.06 mg kg-1. An isobolographic analysis was used to evaluate the sedative interaction of the intraperitoneal co-administration of 1:1 fixed-ratio combination of equi-effective doses of valerian extract with each CNS depressant drug. The ED50 theoretical (Zadd) and experimental (Zexp) for each combination were: valerian+diazepam,Zadd=91.41 mg kg-1, Zexp=81.64 mg kg-1; valerian+ethanol, Zadd=1060.22 mg kg-1, Zexp=687.89 mg kg-1; valerian+pentobarbital, Zadd=96.74 mg kg-1, Zexp=151.83 mg kg-1; valerian+buspirone, Zadd=91.33 mg kg-1, Zexp=112.73 mg kg-1; valerian+haloperidol, Zadd=91.01 mg kg-1, Zexp=91.52 mg kg-1; valerian+diphenhydramine, Zadd=99.34 mg kg-1, Zexp=123.52 mg kg-1. Neither synergistic nor attenuate effects were found in any of the combinations evaluated. We concluded that the valerian extract did not potentiate the sedative effect of commonly prescribed CNS depressant drugs as was expected. The additive effect found through the isobolographic analysis suggested that the sedative effect of V. edulis resulted from the activation of common mechanisms of haloperidol, diazepam, buspirone, pentobarbital, diphenhydramine and ethanol.

  13. Effects of 5-HT1A receptor agonists and L-5-HTP in Montgomery's conflict test. (United States)

    Söderpalm, B; Hjorth, S; Engel, J A


    The effects of the pyrimidinyl-piperazines buspirone, gepirone, ipsapirone and their common metabolite 1-(2-pyrimidinyl)-piperazine (PmP) as well as of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and L-5-hydroxytryptophan (L-5-HTP) were investigated in Montgomery's conflict test--an animal anxiety model based on the animal's inborn urge to explore a new environment and its simultaneous fear of elevated, open spaces. Subcutaneous buspirone (32-128 nmol/kg), gepirone (32-128 nmol/kg), ipsapirone (32-512 nmol/kg) and 8-OH-DPAT (50-200 nmol/kg), as well as intraperitoneal L-5-HTP (56 mumol/kg) produced anxiolytic-like effects. However, at higher doses the magnitude of these effects decreased and overall the dose-response curves displayed inverted U-shapes. The highest doses (2048 nmol/kg) of buspirone and of gepirone even decreased responding below control levels, possibly in part due to concomitant sedation/motor impairment. After L-5-HTP (448 mumol/kg) and PmP (512 nmol/kg) anxiogenic-like effects were observed. The results indicate that anxiolytic- and anxiogenic-like effects of drugs affecting central serotonergic neurotransmission can be obtained in a sensitive rat anxiety model which neither involves consummatory behavior nor punishment. The anxiolytic-like effects of these compounds may be due to their 5-HT1A agonistic properties. Moreover, the present data may provide support for a possible reciprocal association of presynaptic 5-HT1A receptors vs. postsynaptic 5-HT1A as well as 5-HT2 receptors with regard to anxiety.

  14. Involvement of serotonin and oxytocin in neural mechanism regulating amicable social signal in male mice: Implication for impaired recognition of amicable cues in BALB/c strain. (United States)

    Arakawa, Hiroyuki


    Social signals play a primary role in regulating social relationships among male mice. The present series of experiments investigated the neural mechanisms underlying an induction of amicable cues that facilitate social approach in male mice of the C57BL/6 (B6) and BALB/c (BALB) strains. Male mice exhibit approach behavior and suppression of territorial scent marking toward amicable counterparts. Exposure of a group-housed mouse that maintains an amicable relationship induced social approach in B6 recipient mice, as expressed by increased preference of stay in proximity and decreased scent marks relevant to those of a single-housed mouse. Nasal administration of oxytocin (OT) to stimulus mice appeared to enhance social approach in B6 recipient mice. Systemic administration of buspirone (5-HT1A agonist) to stimulus mice also increased approach in B6 recipient mice, whereas a nasal OT antagonist infusion followed by systemic buspirone injection of stimulus mice blocked this buspirone-induced approach in B6 recipient mice. BALB mice likely possess an intact signaling system as shown in B6 mice, in which the 5-HT → OT pathway is a primary modulator for social amicable signals. However, BALB mice could not exhibit signal-dependent change in approach behavior. No impairment in olfactory discrimination or approach behavior toward social stimuli was found in BALB mice. It is concluded that social cues for facilitating social approach are eliminated via the 5-HT → OT pathway, and BALB mice as a low social strain have a deficit in recognition of specific signals associated with amicability. (PsycINFO Database Record

  15. Effects of injection of serotonin into nucleus caudatus on food and water intake and body weight in albino rats. (United States)

    Pal, G K; Kannan, N; Pal, Pravati


    Serotonin is known to inhibit food and water intake. However, the effect of its injection into nucleus caudatus on food and water intake is not known. In the present study, serotonin hydrochloride, buspirone (the serotonin 5-HT1A agonist) and ondensetron (the 5HT3 antagonist) were injected into nucleus caudatus through stereotaxically implanted cannulae in three different dosages (1, 2 and 5 microg) and their effects on 24 h food and water intake, and body weight were recorded. The injection of serotonin hydrochloride resulted in a dose- dependent decrease in food intake attaining maximum of 27.3% at 5 microg dose, whereas water intake and body weight were decreased 12% and 4.3% respectively only at the highest does. Buspirone elicited a dose dependent inhibition of food and water intake and body weight (22.3%, 19.8% and 5.1% respectively), whereas ondensetron elicited an increase in food and water intake (37.8% and 36.3% respectively) without significantly altering bodyweight. It was concluded that serotonin hydrochloride injected into nucleus caudatus inhibits food and water intake significantly. These effects are mediated via 5-HT1A and 5HT3 receptors. The effect of injections of 5-HT1A receptor agonist is more pronounced on water intake. The effect of injections of 5HT3 receptor antagonist is also more pronounced on water intake.

  16. 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:; Gunn, Roger N.; Wilkins, Martin R.; Sargent, Peter A.; Mocaer, Elizabeth; Sedman, Ewen; Cowen, Philip J.; Grasby, Paul M


    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.

  17. What happens to anxiety disorders in later life?

    Directory of Open Access Journals (Sweden)

    Byrne Gerard JA


    Full Text Available Anxiety disorders decline in prevalence with advancing age but remain more common than depressive disorders. They are often of late-onset and there is frequent comorbidity with depressive disorders and physical illness. While anxiety disorders in older people are likely to respond to the same non-pharmacological interventions that have been shown to work in younger people, there is currently little formal evidence of this. Although there is some evidence that the non-benzodiazepine anxiolytic medication, buspirone, is effective against late life anxiety symptoms, clinical trials in older people with rigorously diagnosed anxiety disorders are needed. An anxiety scale with demonstrated reliability and validity in older people is needed for screening for pathological anxiety and for measuring change in older patients undergoing treatment for anxiety disorders.

  18. The alarm pheromone in male rats as a unique anxiety model: psychopharmacological evidence using anxiolytics. (United States)

    Inagaki, Hideaki; Kiyokawa, Yasushi; Takeuchi, Yukari; Mori, Yuji


    Previously, we demonstrated that an alarm pheromone released from male donor Wistar rats evoked anxiety-related physiological and behavioral responses in recipient rats. Thus, we believe that this pheromone may increase anxiety levels in rats. In the current study, we evaluated the predictive validity of this alarm pheromone-induced anxiogenic effect in detail by investigating whether six types of human anxiolytics, each of which has a different mechanism of action, were efficacious in reducing anxiety, using changes in the acoustic startle reflex (ASR) as an index. The alarm pheromone-enhanced ASR was not affected by vehicle pretreatment but was dose-dependently attenuated by pretreatment with midazolam, phenelzine, propranolol, clonidine, and CP-154,526-although not buspirone. These results may reflect some aspects of the predictive validity of the alarm pheromone-induced anxiety in rats as an animal model of human anxiety.

  19. Developing strategies for isolation of minor impurities with mass spectrometry-directed fractionation. (United States)

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


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

  20. 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


    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......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......-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...

  1. The GABA(B) receptor positive modulator BHF177 attenuated anxiety, but not conditioned fear, in rats. (United States)

    Li, Xia; Kaczanowska, Katarzyna; Finn, M G; Markou, Athina; Risbrough, Victoria B


    GABAB (γ-aminobutyric acid B) receptors may be a therapeutic target for anxiety disorders. Here we characterized the effects of the GABAB receptor positive allosteric modulator (PAM) BHF177 on conditioned and unconditioned physiological responses to threat in the light-enhanced startle (LES), stress-induced hyperthermia, and fear-potentiated startle (FPS) procedures in rats. The effects of BHF177 on LES were compared with those of the GABAB receptor agonists baclofen and CGP44532, and the positive control buspirone, a 5-HT1A receptor partial agonist with anxiolytic activity in humans. Baclofen (0.4, 0.9 and 1.25 mg/kg) and CGP44532 (0.065, 0.125 and 0.25 mg/kg) administration had significant sedative, but not anxiolytic, activity reflected in overall decrease in the startle response in the LES tests. BHF177 (10, 20 and 40 mg/kg) had no effect on LES, nor did it produce an overall sedative effect. Interesting, however, when rats were grouped by high and low LES responses, BHF177 had anxiolytic-like effects only on LES in high, but not low, LES responding rats. BHF177 also blocked stress-induced hyperthermia, but had no effect on conditioned fear responses in the FPS test. Buspirone (1 and 3 mg/kg) had an anxiolytic-like profile in both LES and FPS tests. These results indicate that BHF177 may specifically attenuate unconditioned anxiety in individuals that exhibit a high anxiety state, and has fewer sedative effects than direct agonists. Thus, BHF177 or other GABAB receptor PAMs may be promising compounds for alleviating increased anxiety seen in various psychiatric disorders with a superior side-effect profile compared to GABAB receptor agonists.

  2. Mice behavioural models with pooled data analysis of Gelsemium studies and new findings about Ignatia and Aconitum

    Directory of Open Access Journals (Sweden)

    Anita Conforti


    Full Text Available Objective: We investigated the effects of three different homeopathic medicines in several dilutions/dynamizations on mice, using validated models which explore anxiety-like and emotional symptoms. Two complete series of investigations were performed in order to assess the activity of Gelsemium sempervirens; furthermore, we investigated Ignatia amara and Aconitum napellus in the same model systems. Methods: Mice of CD1 strain were randomized in different cages (minimum 8 mice per treated group in each experiment and treatment solutions were coded in such a way that all protocols were carried out fully in blind. The indicated compounds at various centesimal dilutions/dynamizations, a control solution (the solvent vehicle of drugs, which was succussed before administration or the reference drugs diazepam (1 mg/kg body weight or buspirone (5 mg/kg body weight diluted in the same succussed solvent were delivered intraperitoneally (0.3 ml/mice for 9 days. A series of changes of animal behavior were assessed by the Light-Dark (LD choice test and the Open-Field (OF exploration test. Two series of studies with little technical differences, exploiting a total of 14 separate experiments, were carried out with Gelsemium, five complete experiments with Ignatia and four complete experiments with Aconitum. Results: In both series of experiments Gelsemium showed anxiolytic-like effects using both OF test (permanence and movement in centre area of field and LD test (time spent in lit area and number of light-dark transitions. However, due to high variability of animal responses and possibly to some minor differences in protocols, those effects reached the threshold of statistical significance only in OF in the first series and only in LD in the second series. Cumulative analysis of the two series demonstrated a highly significant (p<0.0001 effect of Gelsemium 5CH,7CH, and 30CH in OF parameters and of Gelsemium 5CH, 9CH, and 30CH in LD parameters. In OF the

  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


    , 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. [Regulation of the central opioidergic nervous system on the emotional state of anxiety and its possible mechanisms]. (United States)

    Zhang, H T


    The spontaneous withdrawal from morphine in morphine-dependent rats significantly decreased the duration of active interaction in social interaction test and the number of licks during the shock-punished period in Vogel's conflict procedure, which were attenuated by buspirone, a 5-HT1A agonist, as well as para-chlorophenylalanine (PCPA), an inhibitor of tryptophan hydroxylase. Naltrexone (NTX), a potent opioid receptor antagonist, also dose- and time-dependently reduced both indices mentioned above, which was blocked by morphine or PCPA and was enhanced by 5-hydroxytryptophan, a precursor of 5-HT. In the test of neurotransmitter releases in rat brain slices, both morphine-withdrawal and NTX enhanced high potassium(30mM)-induced 5-HT release in slices of the area of the raphe nucleus. These results suggested that both morphine-withdrawal and NTX produced anxieties in morphine-dependent and normal rats, respectively, which were mediated by the central 5-HTergic neurotransmission. Central opioidergic neurons inhibited 5-HTergic neurons tonically and presynaptically. Such an effect was reduced or blocked by NTX, or during morphine-withdrawal, and 5-HTergic neurons were disinhibited, leading to a state of anxiety.

  5. An improved human anxiety process biomarker: characterization of frequency band, personality and pharmacology. (United States)

    Shadli, S M; Glue, P; McIntosh, J; McNaughton, N


    Anxiety disorders are among the most common mental illness in the western world with a major impact on disability. But their diagnosis has lacked objective biomarkers. We previously demonstrated a human anxiety process biomarker, goal-conflict-specific electroencephalography (EEG) rhythmicity (GCSR) in the stop-signal task (SST). Here we have developed and characterized an improved test appropriate for clinical group testing. We modified the SST to produce balanced numbers of trials in clearly separated stop-signal delay groups. As previously, right frontal (F8) GCSR was extracted as the difference in EEG log Fourier power between matching stop and go trials (that is, stop-signal-specific power) of a quadratic contrast of the three delay values (that is, power when stopping and going are in balanced conflict compared with the average of when stopping or going is greater). Separate experiments assessed drug sensitivity (n=34) and personality relations (n=59). GCSR in this new SST was reduced by three chemically distinct anxiolytic drugs (administered double-blind): buspirone (10 mg), triazolam (0.25 mg) and pregabalin (75 mg); had a frequency range (4-12 Hz) consistent with rodent model data; and positively correlated significantly with neuroticism and nonsignificantly with trait anxiety scores. GCSR, measured in our new form of the SST, should be suitable as a biomarker for one specific anxiety process in the testing of clinical groups and novel drugs and in the development of measures suitable for individual diagnosis.

  6. Gepirone. Organon. (United States)

    Leslie, R A


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

  7. Effects of 5-HT1A receptor agonists and NMDA receptor antagonists in the social interaction test and the elevated plus maze. (United States)

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


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

  8. Duloxetine-induced Sleep Bruxism in Fibromyalgia Successfully Treated With Amitriptyline

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    Şule Şahin Onat


    Full Text Available A 44-year-old woman, who was suffering from widespread musculoskeletal pain, fatigue, and sleep disorder, was diagnosed as fibromyalgia. There was no apparent organic disease. Duloxetine therapy was introduced with a dose of 60 mg/day at bedtime. A few days later her husband noted severe teeth clenching and associated loud grinding noises during sleep. Then, duloxetine dosage was reduced to 30 mg/day. The bruxism continued with this dosage, thus the therapy was discontinued. The bruxism resolved after cessation. Three weeks later, duloxetine therapy was restarted at the dosage of 60 mg/day. On the third day of the therapy, bruxism started again and amitriptyline therapy at the dosage of 10 mg/day was added to duloxetine therapy. The dosage of amitriptyline was incrementally adjusted to 25 mg/ day. On the fourth day of the combined therapy, bruxism symptoms improved. Two months later, the bruxism symptoms were resolved and the complaints for fibromyalgia were under control. Although bruxism has been reported due to venlafaxine use, there is only one duloxetine-induced bruxism case in the literature which was treated with buspirone. However, we report duloxetine-induced bruxism treated successfully with amitriptyline in a patient with fibromyalgia. Tricyclic antidepressants have a suppression effect on the REM phase of the sleep cycle; this may help to cease the bruxism symptoms appearing in that phase of the sleep cycle. This is the first reported case of fibromyalgia with duloxetine-induced sleep bruxism successfully treated with amitriptyline.

  9. Color Preference in Danio rerio: Effects of Age and Anxiolytic Treatments. (United States)

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


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

  10. Gabapentin-induced delirium and dependence. (United States)

    Kruszewski, Stefan P; Paczynski, Richard P; Kahn, David A


    Gabapentin (Neurontin) is approved by the US Food and Drug Administration for treatment of epilepsy and post-herpetic neuralgia. Despite lack of strong evidence, gabapentin is also often prescribed off-label for psychiatric conditions. The case described here involved a 38-year-old male physician with substance intoxication delirium and psychoactive substance dependence due to high self-administered doses of gabapentin, which had been prescribed at lower doses in combination with buspirone and bupropion for depression and anxiety. This unusual case of gabapentin dependence and abuse involved toxic delirium, intense cravings, and a prolonged post-withdrawal confusional state reminiscent of benzodiazepine withdrawal. Gabapentin is a central nervous system inhibitory agent with likely gamma-aminobutyric acid (GABA)-ergic and non-GABAergic mechanisms of action. The similarity between benzodiazepine withdrawal and what this patient experienced with gabapentin suggests a common role for GABA-related effects. The case reported here suggests the need for heightened concern regarding the off-label prescription of this drug to vulnerable individuals with psychiatric conditions.

  11. LC-ESI-MS/MS analysis and pharmacokinetics of 6'-hydroxy justicidin A, a potential antitumor active component isolated from Justicia procumbens, in rats. (United States)

    Qiu, Feng; Zhou, Shujun; Fu, Shujun; Kong, Weijun; Yang, Shihai; Yang, Meihua


    A sensitive and accurate LC-ESI-MS/MS method was developed and validated of for the determination of 6'-hydroxy justicidin A (HJA), a potential antitumor active component isolated from Justicia procumbens in rat plasma using a simple liquid-liquid extraction (LLE) method for sample preparation. Chromatographic separation was achieved on an Agilent Zorbax-C(18) column (2.1 mm × 50 mm, 3.5 μm) using a step gradient program with the mobile phase of 0.1% formic acid aqueous solution and acetonitrile with 0.1% formic acid. HJA and IS (buspirone) were detected using electrospray positive ionization mass spectrometry in the multiple reaction monitoring (MRM) mode. This method demonstrated good linearity and did not show any endogenous interference with the active compound and IS peaks. The lower limit of quantification (LLOQ) of HJA was 0.50 ng/ml in 50 μl rat plasma. The developed and validated method has been successfully applied to the quantification and pharmacokinetic study of HJA in rats after intravenous and oral administration of 0.25 mg/kg HJA. The oral bioavailability (F) of HJA was estimated to be 36.0±13.4% with an elimination half-life (t(1/2)) value of 1.04±0.20 h.

  12. New drug treatments for alcohol problems: a critical appraisal. (United States)

    Moncrieff, J; Drummond, D C


    This review considers the novel drug treatments that have been suggested to help prevent relapse or attenuate drinking in people with alcohol problems. The evidence from randomized controlled trials for the efficacy of some of the main candidates: acamprosate, naltrexone, bromocriptine, selective serotonin re-uptake inhibitors and buspirone, was examined. Important methodological problems which may have introduced bias were detected in many of the trials. These included failure to test the integrity of the double blind, excluding or estimating outcome in early withdrawals and the comparison of groups on multiple outcome measures with selective reporting of results. In addition, the generalizability of some studies was limited by the procedures used for sample selection. In view of the potential adverse effects of drug treatment it is concluded that the evidence is not strong enough to support the introduction of any of these substances into routine clinical practice at present. The review also emphasizes the importance of methodological rigour to maximize objectivity in treatment evaluation research.

  13. Management of psychotropic-induced hyperprolactinemia. (United States)

    Marken, P A; Haykal, R F; Fisher, J N


    The effects of individual psychotropic medications on serum prolactin concentrations are described, and recommendations for dealing with adverse effects are provided. Hyperprolactinemia can result in galactorrhea, amenorrhea, irregular menses, and anovulation; in men, impotence and azoospermia, with or without lactation and gynecomastia, can occur. Antipsychotics may block dopamine receptors in the pituitary prolactin-secreting cells and prevent dopamine-induced reduction of prolactin release. The magnitude of the increase in prolactin concentration correlates with the amount of antipsychotic drug given. The treatment of choice is reduction of the antipsychotic dosage or discontinuation of therapy. If adjustments to the antipsychotic dosage fail to resolve symptoms, the dopamine agonists bromocriptine and amantadine may be tried. Antidepressants may produce elevated serum prolactin concentrations, especially with long-term administration. However, the frequency of antidepressant-induced hyperprolactinemia is much lower than that seen with antipsychotics, and serious adverse clinical effects are uncommon. Other psychotropic drugs such as lithium, valproic acid, buspirone, carbamazepine, and benzodiazepines either are only rarely associated with symptomatic hyperprolactinemia or do not produce clinically important changes in prolactin concentrations. Antipsychotic drugs are the psychotropic agents most likely to cause symptomatic hyperprolactinemia. Bromocriptine or amantadine may provide symptomatic relief if withdrawal or adjustment of the antipsychotic dosage does not eliminate the symptoms.

  14. Involvement of central serotonergic systems in dextromethorphan-induced behavioural syndrome in rats. (United States)

    Gaikwad, R V; Gaonkar, R K; Jadhav, S A; Thorat, V M; Jadhav, J H; Balsara, J J


    Dextromethorphan, a noncompetitive blocker of the N-methyl-D-aspartate (NMDA) type of glutamate receptor, at 45, 60 and 75 mg/kg, ip doses induced a behavioural syndrome characterised by reciprocal forepaw treading, lateral head-weaving, hind-limb abduction and flat body posture. Such type of behavioural syndrome is induced by 8-hydroxy-2- (di-n-propylamino) tetralin (8-OH-DPAT) by directly stimulating the central postsynaptic 5-hydroxytryptamine (5-HT, serotonin) receptors of the 5-HT1A type. Pretreatment with buspirone (5, 10 mg/kg, ip) and l-propranolol (10, 20 mg/kg, ip) antagonised the behavioural syndrome induced by 8-OH-DPAT and dextromethorphan. Pretreatment with p-chlorophenylalanine (100 mg/kg/day x 4 days) antagonised the behavioural syndrome induced by dextromethorphan and dexfenfluramine but had no significant effect on 8-OH-DPAT induced behavioural syndrome. This indicates that dextromethorphan induces the behavioural syndrome by releasing 5-HT from serotonergic neurons with resultant activation of the postsynaptic 5-HT1A receptors by the released 5-HT. Pretreatment with fluoxetine (10 mg/kg, ip) significantly potentiated the behavioural syndrome induced by dextromethorphan and 5-hydroxytryptophan but significantly antagonised dexfenfluramine induced behavioural syndrome. This indicates that dextromethorphan releases 5-HT by a mechanism which differs from that of dexfenfluramine. Dextromethorphan may be releasing 5-HT by blocking the NMDA receptors and thereby counteracting the inhibitory influence of l-glutamate on 5-HT release.

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

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    Sang-Bum Kim


    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.

  16. The Psychopharmacology Algorithm Project at the Harvard South Shore Program: An Algorithm for Generalized Anxiety Disorder. (United States)

    Abejuela, Harmony Raylen; Osser, David N


    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.

  17. Pinelliae Rhizoma, a Toxic Chinese Herb, Can Significantly Inhibit CYP3A Activity in Rats

    Directory of Open Access Journals (Sweden)

    Jinjun Wu


    Full Text Available Raw Pinelliae Rhizoma (RPR is a representative toxic herb that is widely used for eliminating phlegm or treating cough and vomiting. Given its irritant toxicity, its processed products, including Pinelliae Rhizoma Praeparatum (PRP and Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine (PRPZA, are more commonly applied and administered concomitantly with other chemical drugs, such as cough medications. This study aimed to investigate the effects of RPR, PRP, and PRPZA on CYP3A activity. Testosterone (Tes and buspirone (BP were used as specific probe substrates ex vivo and in vivo, respectively. CYP3A activity was determined by the metabolite formation ratios from the substrates. Ex vivo results show that the metabolite formation ratios from Tes significantly decreased, indicating that RPR, PRP, and PRPZA could inhibit CYP3A activity in rats. CYP3A protein and mRNA levels were determined to explore the underlying mechanism. These levels showed marked and consistent down-regulation with CYP3A activity. A significant decrease in metabolite formation ratios from BP was also found in PRPZA group in vivo, implying that PRPZA could inhibit CYP3A activity. Conclusively, co-administration of PR with other CYP3A-metabolizing drugs may cause drug–drug interactions. Clinical use of PR-related formulae should be monitored carefully to avoid adverse interactions.

  18. Flibanserin for hypoactive sexual desire disorder: place in therapy (United States)

    Gelman, Faina; Atrio, Jessica


    The pathophysiology, diagnosis and treatment of female sexual interest in pre- and post-menopausal women present a complex arena for patients and physicians to navigate. Flibanserin was the first pharmacologic treatment, approved by the United States Food and Drug Administration in August 2015, for hypoactive sexual desire disorder (HSDD) in premenopausal women. Side effects, contraindications and lack of approval in postmenopausal women are all limitations, as are issues surrounding patient and physician knowledge and access. Testosterone, buspirone, sildenafil, bupropion, bremelanotide, as well as herbal medications (Herbal vX or Tribulus terrestris) have demonstrated some clinical benefit in women with sexual dysfunction disorders however, trials have significant design, dosing or generalizability limitations. Nonpharmaceutical cognitive behavioral therapy, mindfulness meditation, pelvic floor therapy, and clitoral stimulators are also interventions women may pursue. This manuscript will explore the clinical data regarding these therapeutic modalities so as to bring attention to this issue of female HSDD, to offer an overview of current research, and to incite providers to initiate discussion among themselves and their patients. PMID:28203348

  19. Psychopharmacological neuroprotection in neurodegenerative disease: assessing the preclinical data. (United States)

    Lauterbach, Edward C; Victoroff, Jeff; Coburn, Kerry L; Shillcutt, Samuel D; Doonan, Suzanne M; Mendez, Mario F


    This manuscript reviews the preclinical in vitro, ex vivo, and nonhuman in vivo effects of psychopharmacological agents in clinical use on cell physiology with a view toward identifying agents with neuroprotective properties in neurodegenerative disease. These agents are routinely used in the symptomatic treatment of neurodegenerative disease. Each agent is reviewed in terms of its effects on pathogenic proteins, proteasomal function, mitochondrial viability, mitochondrial function and metabolism, mitochondrial permeability transition pore development, cellular viability, and apoptosis. Effects on the metabolism of the neurodegenerative disease pathogenic proteins alpha-synuclein, beta-amyloid, and tau, including tau phosphorylation, are particularly addressed, with application to Alzheimer's and Parkinson's diseases. Limitations of the current data are detailed and predictive criteria for translational clinical neuroprotection are proposed and discussed. Drugs that warrant further study for neuroprotection in neurodegenerative disease include pramipexole, thioridazine, risperidone, olanzapine, quetiapine, lithium, valproate, desipramine, maprotiline, fluoxetine, buspirone, clonazepam, diphenhydramine, and melatonin. Those with multiple neuroprotective mechanisms include pramipexole, thioridazine, olanzapine, quetiapine, lithium, valproate, desipramine, maprotiline, clonazepam, and melatonin. Those best viewed circumspectly in neurodegenerative disease until clinical disease course outcomes data become available, include several antipsychotics, lithium, oxcarbazepine, valproate, several tricyclic antidepressants, certain SSRIs, diazepam, and possibly diphenhydramine. A search for clinical studies of neuroprotection revealed only a single study demonstrating putatively positive results for ropinirole. An agenda for research on potentially neuroprotective agent is provided.

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

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    Paul R Albert


    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.

  1. A qualitative method for prediction of amine oxidation in methanol and water. (United States)

    Bäcktorp, Carina; Örnskov, Eivor; Evertsson, Emma; Remmelgas, Johan; Broo, Anders


    We have developed a predictive method, based on quantum chemical calculations, that qualitatively predicts N-oxidation by hydrogen peroxides in drug structures. The method uses linear correlations of two complementary approaches to estimate the activation barrier without calculating it explicitly. This method can therefore be automated as it avoids demanding transition state calculations. As such, it may be used by chemists without experience in molecular modeling and provide additional understanding to experimental findings. The predictive method gives relative rates for N,N-dimethylbenzylamine and N-methylmorpholine in good agreement with experiments. In water, the experimental rate constants show that N,N-dimethylbenzylamine is oxidized three times faster than N-methylmorpholine and in methanol it is two times faster. The method suggests it to be two and five times faster, respectively. The method was also used to correlate experimental with predicted activation barriers, linear free-energy relationships, for a test set of tertiary amines. A correlation coefficient R(2) = 0.74 was obtained, where internal diagnostics in the method itself allowed identification of outliers. The method was applied to four drugs: caffeine, azelastine, buspirone, and clomipramine, all possessing several nitrogens. Both overall susceptibility and selectivity of oxidation were predicted, and verified by experiments.

  2. Daidzin and daidzein suppress free-choice ethanol intake by Syrian golden hamsters. (United States)

    Keung, W M; Vallee, B L


    Syrian Golden hamsters prefer and consume large and remarkably constant amounts of ethanol in a simple two-bottle free-choice regimen. Ethanol intake is significantly suppressed by zimelidine, bromocriptine, buspirone, and lithium carbonate, pharmacological agents that have been shown to be beneficial in controlling ethanol intake in alcohol-dependent humans. These results suggest that this ethanol-drinking animal model has high "predictive validity" and can be used effectively in the search for and identification of new agents for the treatment of alcohol abuse. The model has enabled us to confirm the putative antidipsotropic effect of Radix puerariae (RP), an herb long used in traditional Chinese medicine for the treatment of patients who abuse alcohol. A crude extract of RP at a dose of 1.5 x day-1 significantly suppresses (> 50%) the free-choice ethanol intake of Golden hamsters. Moreover, two major constituents of RP, daidzein (4',7-dihydroxyisoflavone) and daidzin (the 7-glucoside of daidzein), were also shown to suppress free-choice ethanol intake. Daidzin and daidzein, at doses of 150 and 230 x day-1, respectively, suppress ethanol intake by > 50%. RP, daidzein, and daidzin treatment do not significantly affect the body weight and water or food intake of the hamsters. These findings identify a class of compounds that offer promise as safe and effective therapeutic agents for alcohol abuse.

  3. Comparison of TiO2 photocatalysis, electrochemically assisted Fenton reaction and direct electrochemistry for simulation of phase I metabolism reactions of drugs. (United States)

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


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

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

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    Roberto Andreatini


    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.

  5. 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


    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

  6. The Preclinical and Clinical Effects of Vilazodone for the Treatment of Major Depressive Disorder (United States)

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


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

  7. Tardive Dyskinesia Revisited: A Clinical Priority Perspective-Diagnosis and Assessment (Part A

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    Vernon M Neppe


    Full Text Available In this series of papers under the umbrella of tardive dyskinesia (TD, five major related issues are discussed pertaining to TD. These are integrated together. In Part A we evaluate how to diagnose, screen for physical signs and scales for tardive dyskinesia, and in Part B, we focus on the management. Tardive dyskinesia (TD is a relatively new condition associated with abnormal involuntary movements caused by or aggravated by so-called “neuroleptic” drugs. Neuroleptics are used to manage psychotic conditions, as well as nausea and acid reflux, and latterly are prescribed as adjunct medications to depression and anxiety. Tardive dyskinesia (TD has also become a major problem forensically, because of the challenge of management, the lack of patient’s being appropriately warned, and insufficient monitoring of patients at risk. In this Part A series of articles we examine several special important priorities in TD. a. First, what is tardive dyskinesia and how does one make the diagnosis? b. The second issue is the need to regularly evaluate patients on neuroleptics because they are at risk for tardive dyskinesia. Measuring and monitoring for symptoms of tardive dyskinesia allows ensuring early detection. The author’s clinical STRAW test has thus far been seldom used, but it may be the best way to monitor TD over time. It appears an improvement over the standard test, the AIMS, as it is broader in ranking (0-10 and is the only scale that measures both frequency and severity, so that monitoring of change is more sensitive. In the series that follows, Part B, we emphasize management and theory, particularly high dose buspirone management, justify the dopamine super sensitivity hypothesis, and re-evaluate the neuroleptics in that context. e1

  8. An Automated High-Throughput Metabolic Stability Assay Using an Integrated High-Resolution Accurate Mass Method and Automated Data Analysis Software (United States)

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


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

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

    Neuvonen, Pertti J


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

  10. Pharmacological evaluation of the stress-induced social avoidance model of anxiety. (United States)

    Leveleki, Cs; Sziray, N; Levay, G; Barsvári, B; Soproni, K; Mikics, E; Haller, J


    We have shown earlier that mild electric shocks induce a lasting social avoidance in male rats. Here we investigated whether shock-induced social avoidance can be developed into a laboratory model of stress-induced anxiety. The putative new model would assess sub-chronic, stress-induced anxiety (as opposed to tests based on natural fear) in a heterologous context (as opposed to classical fear conditioning). A single exposure to mild electric shocks induced a robust social avoidance that lasted more than 5 days. Low doses of chlordiazepoxide (0.5, 1 mg/kg), diazepam (0.5, 1, 5 mg/kg), buspirone (0.3, 1 mg/kg), and fluoxetine (1, 3, 5 mg/kg) abolished this effect, whereas the anxiogenic compound m-chlorophenylpiperazine (0.5-3 mg/kg) induced social avoidance in unshocked rats. These effects were produced at doses that did not affect locomotion in the open field. Haloperidol (0.05, 0.1, 1, 5 mg/kg) influenced social avoidance at sedative doses only. The sensitivity of the model to anxiolytic agents was compromised at high (sedating) doses. Taken conjointly, these data show that shock-induced social avoidance can be used to assess the anxiolytic potential of compounds. In addition to predictive validity, the model appears to show construct and face validity as well: stress is among the etiological factors of, whereas social avoidance simulates the social deficits seen in, a variety of anxiety disorders. The model may be used to study the effects of anxiolytics on sub-chronic states of stress-induced anxiety.

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

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    Popović-Đorđević Jelena B.


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

  12. Application of a cocktail approach to screen cytochrome P450 BM3 libraries for metabolic activity and diversity. (United States)

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


    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.

  13. Prototypical anxiolytics do not reduce anxiety-like behavior in the open field in C57BL/6J mice. (United States)

    Thompson, Trey; Grabowski-Boase, Laura; Tarantino, Lisa M


    Understanding and effectively treating anxiety disorders are a challenge for both scientists and clinicians. Despite a variety of available therapies, the efficacy of current treatments is still not optimal and adverse side effects can result in non-compliance. Animal models have been useful for studying the underlying biology of anxiety and assessing the anxiolytic properties of potential therapeutics. The open field (OF) is a commonly used assay of anxiety-like behavior. The OF was developed and validated in rats and then transferred to use in the mouse with only limited validation. The present study tests the efficacy of prototypical benzodiazepine anxiolytics, chlordiazepoxide (CDP) and diazepam (DZ), for increasing center time in the OF in C57BL/6J (B6) mice. Multiple doses of CDP and DZ did not change time spent in the center of the OF. Increasing illumination in the OF did not alter these results. The non-benzodiazepine anxiolytic, buspirone (BUSP) also failed to increase center time in the OF while the anxiogenic meta-chlorophenylpiperazine (mCPP) increased center time. Additional inbred mouse strains, BALB/cJ (BALB) and DBA/2J (D2) did not show any change in center time in response to CDP. Moreover, evaluation of CDP in B6 mice in the elevated plus maze (EPM), elevated zero maze (EZM) and light dark assay (LD) did not reveal changes in anxiety-like behavior while stress-induced hyperthermia (SIH) was decreased by DZ. Pharmacokinetic (PK) studies suggest that adequate CDP is present to induce anxiolysis. We conclude that the measure of center time in the OF does not show predictive validity for anxiolysis in these inbred mouse strains.

  14. Aspectos farmacológicos, efeitos anticonvulsivantes e neuroprotetores da buspirona

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    Paula Benvindo Ferreira


    Full Text Available A buspirona é o primeiro fármaco da classe das azapironas e a única comercializada no Brasil. O objetivo do presente trabalho foi conduzir uma revisão de literatura sobre os aspectos farmacológicos da buspirona, bem como demonstrar seus efeitos anticonvulsivantes e neuroprotetores no modelo de convulsão induzido por pilocarpina. Para tanto, foi realizada uma revisão da literatura usando as palavraschaves buspirone, action mechanism, pharmacokinetics, indications, adverse effects, nomenclature e structure, por intermédio do MEDLINE e LILACS, bem como foram inseridos os resultados experimentais encontrados em camundongos pré-tratados com buspirona no modelo de convulsão induzido por pilocarpina. A busca incluiu todos os artigos completos, resumos, estudos de caso, pré-clínicos e clínicos nos idiomas português e inglês compreendidos entre os anos de 1982 e 2010. Com base na revisão, pode se perceber que ainda existem muitas questões sem respostas sobre a farmacologia da buspirona. Somente a descrição do mecanismo de ação é insuficiente para explicar todos os efeitos produzidos pela buspirona. Além disso, em nossos estudos farmacológicos demonstramos que a buspirona apresenta efeitos anticonvulsivantes e neuroprotetores em camundongos no modelo de convulsão induzido por pilocarpina. Existem poucas informações na literatura sobre o mecanismo de ação que explicaria os efeitos adversos da buspirona, bem como suas propriedades anticonvulsivantes e neuroprotetoras. Dessa forma, são necessários mais estudos para fornecer as informações necessárias, bem como para esclarecer as suas propriedades farmacológicas, contribuindo com o conhecimento dos profissionais, a fim de prevenir os efeitos adversos durante o tratamento clínico com a buspirona.

  15. 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

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    Deepali Gupta


    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.

  16. Zebrafish assessment of cognitive improvement and anxiolysis: filling the gap between in vitro and rodent models for drug development. (United States)

    Levin, Edward D


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

  17. Effects of direct- and indirect-acting serotonin receptor agonists on the antinociceptive and discriminative stimulus effects of morphine in rhesus monkeys. (United States)

    Li, Jun-Xu; Koek, Wouter; Rice, Kenner C; France, Charles P


    Serotonergic (5-HT) systems modulate pain, and drugs acting on 5-HT systems are used with opioids to treat pain. This study examined the effects of 5-HT receptor agonists on the antinociceptive and discriminative stimulus effects of morphine in monkeys. Morphine increased tail-withdrawal latency in a dose-related manner; 5-HT receptor agonists alone increased tail-withdrawal latency at 50 °C but not 55 °C water. The antinociceptive effects of morphine occurred with smaller doses when monkeys received an indirect-acting (fenfluramine) or direct acting (8-OH-DPAT, F13714, buspirone, quipazine, DOM, and 2C-T-7) agonist. The role of 5-HT receptor subtypes in these interactions was confirmed with selective 5-HT(1A) (WAY100635) and 5-HT(2A) (MDL100907) receptor antagonists. None of the 5-HT drugs had morphine-like discriminative stimulus effects; however, fenfluramine and 5-HT(2A) receptor agonists attenuated the discriminative stimulus effects of morphine and this attenuation was prevented by MDL100907. The 5-HT(1A) receptor agonists did not alter the discriminative stimulus effects of morphine. Thus, 5-HT receptor agonists increase the potency of morphine in an assay of antinociception, even under conditions where 5-HT agonists are themselves without effect (ie, 55 °C water), without increasing (and in some cases decreasing) the potency of morphine in a drug discrimination assay. Whereas 5-HT(2A) receptor agonists increase the potency of morphine for antinociception at doses that have no effect on the rate of operant responding, 5-HT(1A) receptor agonists increase the potency of morphine only at doses that eliminate operant responding. These data suggest that drugs acting selectively on 5-HT receptor subtypes could help to improve the use of opioids for treating pain.

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

    Pittman, Julian T; Ichikawa, Katie M


    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.

  19. The role of the subthalamic nucleus in L-DOPA induced dyskinesia in 6-hydroxydopamine lesioned rats.

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    Asier Aristieta

    Full Text Available L-DOPA is the most effective treatment for Parkinson's disease (PD, but prolonged use leads to disabling motor complications including dyskinesia. Strong evidence supports a role of the subthalamic nucleus (STN in the pathophysiology of PD whereas its role in dyskinesia is a matter of controversy. Here, we investigated the involvement of STN in dyskinesia, using single-unit extracellular recording, behavioural and molecular approaches in hemi-parkinsonian rats rendered dyskinetic by chronic L-DOPA administration. Our results show that chronic L-DOPA treatment does not modify the abnormal STN activity induced by the 6-hydroxydopamine lesion of the nigrostriatal pathway in this model. Likewise, we observed a loss of STN responsiveness to a single L-DOPA dose both in lesioned and sham animals that received daily L-DOPA treatment. We did not find any correlation between the abnormal involuntary movement (AIM scores and the electrophysiological parameters of STN neurons recorded 24 h or 20-120 min after the last L-DOPA injection, except for the axial subscores. Nonetheless, unilateral chemical ablation of the STN with ibotenic acid resulted in a reduction in global AIM scores and peak-severity of dyskinesia. In addition, STN lesion decreased the anti-dyskinetogenic effect of buspirone in a reciprocal manner. Striatal protein expression was altered in dyskinetic animals with increases in ΔFosB, phosphoDARPP-32, dopamine receptor (DR D3 and DRD2/DRD1 ratio. The STN lesion attenuated the striatal molecular changes and normalized the DRD2/DRD1 ratio. Taken together, our results show that the STN plays a role, if modest, in the physiopathology of dyskinesias.

  20. Dopamine D3 receptor ligands for drug addiction treatment: update on recent findings. (United States)

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


    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.

  1. Rationale for assessing safety and efficacy of drug candidates alone and in combination with medical devices: The case study of SpinalonTM. (United States)

    Guertin, Pierre A


    The aim of this review is to describe the rationale and main underlying reasons for undertaking, during clinical development, the study of drug candidates used separately and/or in combination with other technologies. To ease comprehension, reference will be made to the case of SpinalonTM, a new fixed-dose combination (FDC) product composed of levodopa/carbidopa/buspirone. This drug is capable of triggering, within minutes after a single administration orally, 45 minute- episodes of basic involuntary 'reflex' walking in paraplegic animals. Daily administration during one month was shown to lead to increased performance over time, with health benefits onto musculoskeletal and cardiovascular systems. A double-blind, dose-escalation, randomized phase I/IIa study with 45 spinal cord-injured subjects successfully provided the maximal tolerated dose (MTD) and preliminary evidence of efficacy. As an attempt to explore how efficacy may be optimized, a phase IIb study with 150 subjects was designed to compare the effects of repeated administration in different conditions (arms). Tests with a motorized treadmill, a harness for body weight support, a transdermal spinal cord stimulator and/or an exoskeleton were proposed because: 1) these devices are unlikely to alter safety but, 2) they are reasonably expected to increase spinal locomotor neuron activation, reflex walking induction, and musculoskeletal/cardiovascular benefits. This approach would normally allow the phase III study to demonstrate clearly, with fewer subjects and at lower costs, long-term benefits on health of SpinalonTM used in optimized conditions and settings. This innovative strategy in drug development may contribute to further describe the mechanisms of action as well as optimized conditions of use for patients. Adapted to the development of other products, such an approach may enable greater safety, efficacy, clinical utility and compliance to be sought for next-generation CNS drugs.

  2. An Orally Active Phenylaminotetralin-Chemotype Serotonin 5-HT7 and 5-HT1A Receptor Partial Agonist that Corrects Motor Stereotypy in Mouse Models. (United States)

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


    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.

  3. Pharmacological Treatments of Alzheimer’s Disease: Current Medication,

    Directory of Open Access Journals (Sweden)

    Arash Mowla


    Full Text Available Background: Alzheimer’s disease (AD that is identified by progressive cognitive deficit and behavioral disturbances (BD are the most common form of dementia. As the population is aging, patients with AD are becoming a serious burden for societies. In this study, current medication for cognitive deficit and behavioral disturbances are reviewed. Also the new treatment strategies for cognitive dysfunction and behavioral disturbances are surveyed. Methods: The method employed in this researh was a systematic bibliographic review, in which only the double-blind placebo-controlled studies or the clinically detailed enough open-labeled studies using validated scales were retained. Results: The efficacy of cholinesterase inhibitors (Tacrine, Rivastigmine, Donapezil and Galantamine has been demonstrated in several double blind placebo controlled clinical trials. They have shown a mild efficacy in mild to moderate AD. Memantine, a NMDA antagonist is the only drug that has demonstrated mild efficacy in moderate to severe AD in controlled clinical trial. Clinical trials surveying the efficacy of active and passive immunization against B amyloid protoin has halted due to serious adverse events. Studies of inducing neurogenesis in brain of AD patients are preliminary. Antipsychotics have shown efficacy for controlling BD of AD patients but they are associated with adverse events. Except for carbamazepine, there is not enough evidence for other anticanvulsants to be effective for behavioral disturbances of AD patients. A controlled clinical trial and some open studies have shown the efficacy of citalopram for BD. Further studies are needed to confirm the efficacy of other medications like trazadon, buspiron and beta blockers for BD. Conclusion: Cholinesterase inhibitors have demonstrated disappointing results. Memantine is only mildly effective for cognitive deficit. To date, no amyloid-modifying therapy has yet been successful in phase 3 clinical trials

  4. Hypoactive Sexual Desire Disorder: International Society for the Study of Women's Sexual Health (ISSWSH) Expert Consensus Panel Review. (United States)

    Goldstein, Irwin; Kim, Noel N; Clayton, Anita H; DeRogatis, Leonard R; Giraldi, Annamaria; Parish, Sharon J; Pfaus, James; Simon, James A; Kingsberg, Sheryl A; Meston, Cindy; Stahl, Stephen M; Wallen, Kim; Worsley, Roisin


    The objective of the International Society for the Study of Women's Sexual Health expert consensus panel was to develop a concise, clinically relevant, evidence-based review of the epidemiology, physiology, pathogenesis, diagnosis, and treatment of hypoactive sexual desire disorder (HSDD), a sexual dysfunction affecting approximately 10% of adult women. Etiologic factors include conditions or drugs that decrease brain dopamine, melanocortin, oxytocin, and norepinephrine levels and augment brain serotonin, endocannabinoid, prolactin, and opioid levels. Symptoms include lack or loss of motivation to participate in sexual activity due to absent or decreased spontaneous desire, sexual desire in response to erotic cues or stimulation, or ability to maintain desire or interest through sexual activity for at least 6 months, with accompanying distress. Treatment follows a biopsychosocial model and is guided by history and assessment of symptoms. Sex therapy has been the standard treatment, although there is a paucity of studies assessing efficacy, except for mindfulness-based cognitive behavior therapy. Bupropion and buspirone may be considered off-label treatments for HSDD, despite limited safety and efficacy data. Menopausal women with HSDD may benefit from off-label testosterone treatment, as evidenced by multiple clinical trials reporting some efficacy and short-term safety. Currently, flibanserin is the only Food and Drug Administration-approved medication to treat premenopausal women with generalized acquired HSDD. Based on existing data, we hypothesize that all these therapies alter central inhibitory and excitatory pathways. In conclusion, HSDD significantly affects quality of life in women and can effectively be managed by health care providers with appropriate assessments and individualized treatments.

  5. Radiosynthesis and autoradiographic evaluation of [{sup 11}C]NAD-299, a radioligand for visualization of the 5-HT{sub 1A} receptor

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    Sandell, Johan E-mail:; Halldin, Christer; Hall, Haakan; Thorberg, Seth-Olov; Werner, Tom; Sohn, Daniel; Sedvall, Goeran; Farde, Lars


    The selective 5-HT{sub 1A} receptor antagonist NAD-299 ([R]-3-N,N-dicyclobutylamino-8-fluoro-3,4-dihydro-2H-1-benzopyran- 5-carboxamide) was labeled with the positron emitting radionucldie carbon-11. The radioligand was synthesized from NAD-195 ([R]-3-N,N-dicyclobutylamino-8-fluoro-5-trifluoromethylsulfonyloxy-3, 4-dihydro-2H-1-benzopyran) in two radiochemical steps. A palladium-catalyzed reaction of NAD-195 and [{sup 11}C]cyanide was followed by hydrolysis of the carbon-11-labeled nitrile intermediate with basic hydrogen peroxide. The total radiochemical yield, based on [{sup 11}C]CO{sub 2} and corrected for decay, was 20-40%. The specific radioactivity was 24 GBq/{mu}mol (900 Ci/mmol) at end of synthesis, with a radiochemical purity better than 99% and a total synthesis time of 40-45 min. Autoradiographic examination of [{sup 11}C]NAD-299 binding in human brain postmortem demonstrated high binding in hippocampus, raphe nuclei, and neocortex. The binding in the hippocampus was higher than in the neocortex. Within the hippocampus, the densest binding was observed in the CA1 region. [{sup 11}C]NAD-299 binding was inhibited by addition of the 5-HT{sub 1A} receptor ligands WAY-100635, pindolol, ({+-})-8-OH-DPAT, 5-HT, and buspirone, leaving a low background of nonspecific binding. The results indicate that [{sup 11}C]NAD-299 binds specifically to 5-HT{sub 1A} receptors in the human brain in vitro and is a potential radioligand for positron emission tomography (PET) examination of 5-HT{sub 1A} receptors in vivo.

  6. Selective serotonin reuptake inhibitor exposure. (United States)

    Fitzgerald, Kevin T; Bronstein, Alvin C


    more desirable than other antidepressants. The prognosis in animals that receive treatment is excellent. In one retrospective study, there were no deaths in 313 SSRI-poisoned dogs. No characteristic or classic histopathologic lesions result from SSRI toxicosis. Differential diagnoses for SSRI overdose must include ingestions of other serotonergic medications such as phenylpiperidine opioids (fentanyl and tramadol), mirtazapine, buspirone, amitraz, and chlorpheniramine.

  7. Anxiolytic-like effects of carvacryl acetate, a derivative of carvacrol, in mice. (United States)

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


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

  8. Effect of Yi-nao-jie-yu decoction on γ-aminobutyric acid type A receptor in the hippocampus and serum inflammatory factors in a rat model of poststroke anxiety

    Directory of Open Access Journals (Sweden)

    Zhang W


    Full Text Available Wen Zhang,1 Ruizhen Zhao,1 Xiaoli Li,1 Xia Cui,1 Zijun Zhao,1 Yingqiu Mao,2 Fengzhi Wu,3 Qisheng Tang1 1Department of Encephalopathy, The Third Affiliated Hospital, 2Center of Scientific Research, 3Center of Journals, Beijing University of Chinese Medicine, Chaoyang District, Beijing, People’s Republic of China Background: The Yi-nao-jie-yu decoction (YNJYD is a herbal preparation widely used in the clinics of traditional Chinese medicine and has been recently used as an important new therapeutic agent in poststroke anxiety (PSA. The neuroendocrine–immune system plays an important role in PSA mechanisms, although the modulating effects of YNJYD remain unknown. This study investigated the potential effects of YNJYD on the neuroendocrine–immune system in a rat model of PSA.Materials and methods: The PSA model was induced by injecting collagenase (type VII into the right globus pallidus, accompanied by empty water bottle stimulation for 2 weeks. The sham group and the PSA model group were gavaged with saline, while the treatment groups received buspirone (BuSpar or YNJYD. Behavior was evaluated with the open field test and elevated plus maze once a week. Pathological changes were observed by hematoxylin and eosin staining. Serum levels of tumor necrosis factor, interleukin (IL-6, adrenocorticotropic hormone, thyroid stimulating hormone, free triiodothyronine, free thyroxine, IL-1α, and cortisol were detected by radioimmunoassay. Expression of the γ-aminobutyric acid type A receptor (GABAAR α2 subunit was examined by Western blot and real-time polymerase chain reaction.Results: YNJYD-treated rats exhibited significantly better recovery than BuSpar-treated rats at 21 days and 28 days in the open field test and elevated plus maze. Hematoxylin and eosin staining revealed neural repair in the hippocampus in the treatment groups. Serum levels of IL-1α in the YNJYD group were significantly less than those in the model group and the Bu

  9. Chemical stimulants of leaf-trenching by cabbage loopers: natural products, neurotransmitters, insecticides, and drugs. (United States)

    Dussourd, David E


    Larvae of the cabbage looper, Trichoplusia ni (Lepidoptera: Noctuidae), often transect leaves with a narrow trench before eating the distal section. The trench reduces larval exposure to exudates, such as latex, during feeding. Plant species that do not emit exudate, such as Plantago lanceolata, are not trenched. However, if exudate is applied to a looper's mouth during feeding on P. lanceolata, the larva will often stop and cut a trench. Dissolved chemicals can be similarly applied and tested for effectiveness at triggering trenching. With this assay, I have documented that lactucin from lettuce latex (Lactuca sativa), myristicin from parsley oil (Petroselinum crispum), and lobeline from cardinal flower (Lobelia cardinalis) elicit trenching. These compounds are the first trenching stimulants reported. Several other constituents of lettuce and parsley, including some phenylpropanoids, monoterpenes, and furanocoumarins had little or no activity. Cucurbitacin E glycoside found in cucurbits, another plant family trenched by cabbage loopers, also was inactive. Lactucin, myristicin, and lobeline all affect the nervous system of mammals, with lobeline acting specifically as an antagonist of nicotinic acetylcholine receptors. To determine if cabbage loopers respond selectively to compounds active at acetylcholine synapses, I tested several neurotransmitters, insecticides, and drugs with known neurological activity, many of which triggered trenching. Active compounds included dopamine, serotonin, the insecticide imidacloprid, and various drugs such as ipratropium, apomorphine, buspirone, and metoclopramide. These results document that noxious plant chemicals trigger trenching, that loopers respond to different trenching stimulants in different plants, that diverse neuroactive chemicals elicit the behavior, and that feeding deterrents are not all trenching stimulants. The trenching assay offers a novel approach for identifying defensive plant compounds with potential uses

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

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


    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

  11. Modulation of the vagal bradycardia evoked by stimulation of upper airway receptors by central 5-HT1 receptors in anaesthetized rabbits (United States)

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


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

  12. Clinical drugs that interact with St. John's wort and implication in drug development. (United States)

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


    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

  13. Decreases in nestlet shredding of mice by serotonin uptake inhibitors: comparison with marble burying. (United States)

    Li, Xia; Morrow, Denise; Witkin, Jeffrey M


    Methods for detection of anxiolytic-like behavioral effects of serotonin uptake inhibitors are limited. The present study introduces a new quantitative method that permits dose-effect analysis of these compounds. Male NIH Swiss mice were given 60-min access to a piece of cotton gauze and the amount of material not torn into nesting material was weighed. Other groups of mice were individually placed in containers with 20 marbles resting on top of sawdust bedding. The number of marbles buried (2/3) by sawdust after 30 min was counted. Mice were first placed on a 6-rpm rotorod and the number of mice falling off twice in 2 min was measured. Serotonin uptake inhibitors (clomipramine, citalopram, fluoxetine, and venlafaxine) dose-dependently suppressed nestlet shredding and marble burying at doses that were generally without effect on rotorod performance. The amine-based antidepressant agents imipramine and desipramine as well as the selective norepinephrine transport inhibitor nisoxetine produced similar qualitative effects on these behaviors. Anxiolytics (chlordiazepoxide, bretazenil, buspirone, and pentobarbital) produced effects in the nestlet assay that were similar to those reported using another anxiolytic assay in mice (punished responding), whereas these compounds were not active at non-motor-impairing doses in the marble burying assay. The antipsychotic agents chlorpromazine and risperidone generally demonstrated suppression of nestlet shredding and marble burying at doses that impaired rotorod performance. Although d-amphetamine suppressed nestlet shredding and marble burying at doses without effect on the rotorod, d-amphetamine but not fluoxetine stimulated locomotor activity. Both nestlet shredding and marble burying behaviors were generally consistent across five consecutive experimental sessions and fluoxetine did not produce any systematic trends over repeated testing. The methods should have utility in defining pharmacological effects of these compounds

  14. Control Study of Escitalopram and Combined with the Combination of the Treatment of Depression in the Treatment of Depression%抑郁症治疗中单用艾司西酞普兰与合并丁螺环酮的对照研究

    Institute of Scientific and Technical Information of China (English)

    王非; 王朔


    Objective To investigate the Escitalopram combined with buspirone for improving the curative effect of antidepressants. Methods 88 patients with depression were randomly divided into two groups, respectively, Escitalopram combined with the treatment of weeks (study group, n=46) and Escitalopram (control group n=42) for 6 weeks. The clinical efficacy was evaluated by Hamilton Depression Rating Scale (HAMD) and self rating Depression Scale (SDS). Results The study group and the control group were 55.6%and 48.76%(P<0.05), respectively, with the efficiency of 95.5%and 85.4%(P<0.05), respectively. Conclusion Combination of escitalopram and Ding screw ring ketone for depression, the clinical improvement and the onset time is better than with escitalopram.%目的:探讨艾司西酞普兰合并丁螺环酮对于提高抗抑郁药的疗效作用。方法88例抑郁症患者随机分为两组,分别给予艾司西酞普兰合并丁螺环酮(研究组,n=46)和单用艾司西酞普兰(对照组n=42)治疗6周。采用汉密尔顿抑郁量表(HAMD)抑郁自评量表(SDS)评定临床疗效。结果研究组和对照组的显效率分别为55.6%和48.76%(P<0.05),有效率分别为95.5%和85.4%(P<0.05)。结论艾司西酞普兰合并丁螺环酮对于抑郁症疗效的改善及起效时间优于与单用艾司西酞普兰。

  15. [Dependence on benzodiazepines. Clinical and biological aspects]. (United States)

    Pelissolo, A; Bisserbe, J C


    half-life. The relapse develops later with a progressive reapparance of pre-treatment symptoms. In practice recurrence and rebound are often difficult to isolate: recurrence can follow rebound. Different operational criteria of definition for this different entities have been proposed but there is a need for a consensual position. The treatment length, a high daily dose, an alcohol abuse history, a dependent personality and the severity of the psychopathology of the patients have been found to be predictive for the occurrence of withdrawal symptoms. Behavioural therapies (individual or in group) have been proposed with some success for the treatment of benzodiazepine dependence; drug treatment with carbamazepine or imipramine have demonstrated some efficacy. Other drug as buspirone clonidine having anxiolytic properties have not demonstrated efficacy.(ABSTRACT TRUNCATED AT 400 WORDS)

  16. Revista de Revistas.

    Directory of Open Access Journals (Sweden)

    Antonio Nafs


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

  17. Novas drogas no tratamento da dispepsia funcional New drugs for the treatment of functional dyspepsia

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    Luiz Ernesto de Almeida TRONCON


    any evidence of structural abnormalities or organic disease. Current pharmacological treatment of functional dyspepsia is largely empirical and involves anti-secretory or prokinetic drugs. Aims - To review recent advances in the understanding of the mechanisms involved in symptom production in functional dyspepsia, as well as the development of new drugs that may interfere with these mechanisms, which may lead to more rational and effective treatment of this clinical condition. Method - Systematic review of papers published in English for the last 10 years. Results - New drugs that increase propulsive gastroduodenal motor activity include new benzamides similar to cisapride, CCK-A blockers, agonists of opiate receptors and motilin agonists similar to erythromycin. A number of agents, including sumatriptan and buspirone, stimulates serotonin receptors in the myoenteric plexuses and have been shown to increase gastric accommodation to a meal. Finally, a number of new drugs that either increase thresholds for visceral perception or modify sensations is currently under investigation. This includes agents of several groups, such as octreotide, loxiglumide, ondansetron and other serotonin blockers, fedotozine and tricyclic antidepressant at low doses. Conclusions - Although these new drugs may improve the pharmacological approach to the treatment of functional dyspepsia, there is a need for randomized, controlled trials to assess their efficacy. Moreover, difficulties related to the identification of the mechanisms underlying symptoms may limit the utilization of these new drugs.

  18. Pharmacological and endocrinological characterisation of stress-induced hyperthermia in singly housed mice using classical and candidate anxiolytics (LY314582, MPEP and NKP608). (United States)

    Spooren, Will P J M; Schoeffter, Philippe; Gasparini, Fabrizio; Kuhn, Rainer; Gentsch, Conrad


    The stress-induced hyperthermia test is a paradigm developed several years ago to model the expression of autonomic hyperactivity in anxiety. Whereas in the classical stress-induced hyperthermia, cohort removal was used, in a recently described modification of the stress-induced hyperthermia model singly housed mice rather than groups of mice were used. The modification of this model can be summarized as follows: rectal temperature is recorded in singly housed animals at two consecutive time-points (T1 and T2) which are interspaced by a defined time-interval (15 min). Since the value at the second temperature-recording exceeds the value of the initial measure it is the difference between these two core-temperatures which reflects stress-induced hyperthermia. In the present study, the stress-induced hyperthermia paradigm, in its modified design, was evaluated in OF1/IC mice. By comparing the effect of various compounds in both the modified as well as the classical (cohort removal) stress-induced hyperthermia paradigm, a very high correlation was found for the pharmacological sensitivity of the two paradigms. Furthermore, it was demonstrated that other anxiolytics, all known to be active in the classical stress-induced hyperthermia paradigm, such as the benzodiazepines chlordiazepoxide (0.3, 1, 3, 10 mg/kg, p.o.), diazepam (0.1, 0.3, 1, 3 mg/kg, p.o.), clobazam (5 or 10 mg/kg, p.o.) and oxazepam (5 or 10 mg/kg, p.o.) as well as the non-benzodiazepines buspirone (7.5 or 15 mg/kg, p.o.) and ethanol (15% or 30%, 10 ml/kg, p.o.), showed a marked reduction in stress-induced hyperthermia in the modified design. New candidate anxiolytics, i.e. the metabotropic glutamate (mGlu) receptor group 2 agonist LY314582 (1 or 10 mg/kg, p.o.; racemic mixture of LY354740 ((2S,4S)-2-amino-4-(4,4-diphenylbut-1-yl)-pentane-1,5-dioic acid), the metabotropic glutamate 5 receptor antagonist MPEP (1, 7.5, 15 or 30 mg/kg, p.o.; 2-methyl-6-(phenylethynyl)pyridine) and the neurokinin 1 (NK1

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

    Institute of Scientific and Technical Information of China (English)



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

  20. One-day Investigation of Psychotropic Drugs Use for 149 Inpatients in the Psychosomatic Disorder Department%149例心身障碍科住院患者1日精神药物使用调查

    Institute of Scientific and Technical Information of China (English)

    章凤君; 陈晓燕; 孙皎


    Objective: To investigate the one-day use of psychotropic drugs for the patients in the psychosomatic disorder department, and provide guidance for clinical rational medication. Methods: Prescriptions of 149 inpatients were investigated in the psychosomatic disorder department on May 8, 2012 through Hospital Information System (HIS). Results: Top five prescriptions of antidepressants were respectively paroxetine 35(23.49% ) , sertraline 21 ( 14.09% ) , escita-lopram 19(12. 75%) , mirtazapine 17(11.41%) and venlafaxine 15(10. 07%), while the top five anxiolytics were clon-azepam 130(87.25% ) , buspirone hydrochloride 16( 10.74% ), lorazepam 14(9.40% ) , alprazolam 10(6.71% ) and ox-azepam 6(4. 03% ) in order. The antipsychotics that were used most frequently were Sulpiride 68(45. 64% ) , followed by quetiapine 33(22. 15% ), olanzapine 16( 10. 74% ) , risperidone 7(4.70% ) and aripiprazole 3(2.01% ). Simultaneously , inpatients often received a combination of two or three different drugs above in the psychosomatic disorder department. Conclusion: The new generation of antidepressants and anxiolytics which were safe and had fewer side effects were mainly utilized in the psychosomatic disorder department. Most prescriptions in the one - day investigation were rational. However, some problems should be seriously considered, such as high prevalence of Benzodiazepines use, excessive drug combination and lack of the non-medical therapy.%目的:调查某院心身障碍科1日用药情况,为临床合理用药提供客观数据.方法:统计该院心身障碍科2012年5月8日149例住院患者用药信息.结果:抗抑郁药使用频次依次为帕罗西汀35例(23.49%)、舍曲林21例(14.09%)、艾司西酞普兰19例(12.75%)、米氮平17例(11.41%)、文拉法辛15例(10.07%);镇静催眠抗焦虑药前5位的是氯硝西泮130例(87.25%)、丁螺环酮16例(10.74%)、劳拉西泮14例(9.40%)、阿普唑仑10例(6.71%)、奥沙西泮6例(4.03

  1. 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


    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.

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

    Directory of Open Access Journals (Sweden)

    Antonio Egidio Nardi


    . 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.

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

    Institute of Scientific and Technical Information of China (English)

    陈静; 陈传成; 支胜利


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

  4. 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


    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

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

    Institute of Scientific and Technical Information of China (English)

    郑容; 郭洛宁; 王芬


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

  6. Compound Ruikangxin can reverse the structural plasticity of synapses in hippocampus, amygdala and nucleus accumbens in morphine withdrawal rats%复方瑞康欣可逆转吗啡戒断焦虑大鼠海马、杏仁核和伏核突触形态结构的可塑性

    Institute of Scientific and Technical Information of China (English)

    何继锋; 钱刚; 凌锌; 吴明松; 郭萍; 罗素元


    目的 观察复方瑞康欣(CR)对吗啡戒断焦虑大鼠海马、杏仁核和伏核突触形态结构可塑性的影响.方法 雄性SD大鼠84只,随机分为生理盐水对照组、吗啡戒断焦虑模型组、CR 高、中、低剂量组和丁螺环酮组.以剂量递增方式皮下注射吗啡,10 d后自然戒断,于戒断1~3 d CR灌胃治疗后行高架十字迷宫实验.采用透射电镜技术比较各组(6只)突触体视学和界面结构各参数.结果在300 mg/kg和200 mg/kg CR组,大鼠进入开放臂次数的百分比和在开放臂停留时间的百分比明显增加(P<0.01或P<0.05);海马、杏仁核突触的数密度和面密度显著降低(P<0.01),突触连接带平均面积增加(P<0.01或P<0.05),伏核突触数密度降低(P<0.01);海马突触后致密物厚度、突触活性区长度、间隙宽度和界面曲率降低(P<0.01或P<0.05).结论 CR能缓解吗啡依赖戒断所引起的焦虑,其细胞生物学机制可能是逆转吗啡戒断时海马、杏仁核和伏核突触形态结构的可塑性.%Objective To observe effects on both anxiety-like behaviors and structural plasticity of hippocampus,amygdala and nucleus accumbens in morphine withdrawal rats administrated with collocystis of compound Ruikangxin ( CR ). Methods SD rats, 84 in all, were randomly divided into control group, model group, CR groups involving high,middle and low dosages, and buspirone group. Gradually increasing dosages were applied to establish the model of morphine dependence in rats suffered from drugs ( subcutaneous injection ) for 10 days and followed hy collocystis of CR ( 300, 200, and 100 mg/kg, intragastric administration ) for 1-3 days. The elevated plus-maze tests were applied to validate the anxiety-like hehavior in rats. Samples of hippocampus, amygdala and nucleus accumbens ( n = 6 ) were harvested and further observed after preparation for electron microscope sample. Stereological methods and changeable parameters were applied to ensure accurate

  7. Psychotropics use in out-patient clinic of psychiatry: a single-day survey%精神科门诊一日精神药物使用调查

    Institute of Scientific and Technical Information of China (English)

    王来海; 张瑞岭; 马金芳


    and hypnotics/anxiolytics. Results Of 330 patients surveyed (152 males and 178 females), the most common clinical diagnoses were schizophrenia, depression, bipolar disorders, mania, compulsive disorder, neurosis, cerebral disorder, insomnia and anxiety. Of 330 patients, 108 (32.7%) were treated with monotherapy, 212 (64.2%) received multiple medications and 9 (2.7%) wrere on adjunct medications. The most frequently prescribed antipsychotics were clozapine (35 cases, 10.6 %), risperidone (35 cases, 10.6 %), aripiprazole (28 cases, 8.5%), sulphide (26 cases, 7.9%), quetiapine (24 cases, 7.3%) arid ziprasidone (16 cases, 4.8%). And the most commonly prescribed antidepressants were sertraline (33 cases, 10.0%), paroxetine (20 cases, 6.1%), mirtazapine (14 cases, 4.2%), trazodone (14 cases, 4.2%), fluoxetine (14 cases, 4.2%), fluvoxamine (14 cases, 4.2%), venlafaxine (10 cases, 3.0%), mianserin (10 cases, 3.0%) and reboxetine (4 cases, 1.2%). Mood stabilizers in most frequent use was magnesium valproate (14 cases, 4.2%), lithium carbonate (9 cases, 2.7%), sodium valproate (8 cases, 2.4%), oxacarbazepine (5 cases, 1.5%) and lamot-rigine (4 cases, 1.2%). The five frequently prescribed hypnotics/anxiolytics were clonazepam (42 cases, 12.7%), alpra-zolam (36 cases, 10.9 %), lorazepam (24 cases, 7.3%'), buspirone (22 cases, 6.7%') and zopiclone (19 cases, 5.8%). Conclusion The novel atypical antipsychotics and antidepressants have become the mainstay for schizophrenia and depression therapy. Common application of multiple medications it is indicative of the development trend in psychotropics prescription.