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At least 19 recordsLinked to original sources
PubMed1989

Evaluation of buspirone as an antianxiety agent: buspirone and diazepam versus placebo.

Buspirone has previously been demonstrated to be efficacious in the treatment of anxiety. This four-week double-blind parallel study compared buspirone to diazepam and placebo in the treatment of 119 outpatients diagnosed as having generalized anxiety disorder. After a seven-day placebo washout period, eligible patients were randomized to one of three treatment groups. Buspirone (5 mg) and diazepam (5 mg) were administered BID and individually titrated to an optimal therapeutic dose by the end of week two. Buspirone and diazepam were equally effective in reducing Hamilton Anxiety (HAM-A) total and psychic factor scores from baseline values. Buspirone alone was significantly better than placebo in reducing the HAM-A somatic factor score. Sixty-seven percent of both active treatment groups who were classified as "ill" on the baseline global psychopathology rating scale achieved a "not ill" status by study end. There were no significant differences between treatment groups at endpoint on the 56-item Symptom Checklist self-rating scale. Buspirone was demonstrated to be as effective as diazepam in relieving anxiety in this outpatient sample.

Adult↗
PubMed1991

[Effects of buspirone and buspirone-like 1-A-agonists of serotonin on the level of systemic blood pressure].

Experiments on anaesthetized rats showed that buspirone, its structural analogies (ipsapirone, campirone and levopirone) and active metabolite 1-(2-pyrimidinyl)-piperazine (0.1-30 mg/kg i.v.) produced bradycardia, hyperpnea and changed the arterial pressure level. Arterial pressure either increased or decreased that was determined by its initial level. The hypotension produced by all these drugs was of a central origin and mediated by hydroxytryptamine-1A-receptors. The pressor response resulted from activation of predominantly hydroxytryptamine-2-receptors of vascular smooth muscles.

Animals↗
PubMed1992

Putative mechanisms of buspirone-induced antinociception in the rat.

Intraperitoneal administration of the serotonin 5-HT1A agonist, buspirone (1-5 mg/kg), produced dose- and time-related core hypothermia that was coincident with analgesia against a thermally noxious stimulus. Surface body temperature was not altered by buspirone. The 5-HT1A antagonist, NAN-190 (2 mg/kg, s.c.), blocked both hypothermic and analgesic effects, while systemic administration of the opioid antagonist, naloxone (1 mg/kg, s.c.), did not change the pattern of buspirone-induced hypothermia or analgesia. The apparent lack of opioid involvement and the documented role of the 5-HT1A receptor system in neuroendocrine substrates of thermoregulation and pain modulation prompted study of adrenal function in these buspirone-induced effects. Buspirone (5 mg/kg, i.p.) produced significant elevations in plasma epinephrine (EPI) and corticosterone (CST). Bilateral adrenalectomy reduced both control and buspirone-elevated EPI and CST levels and attenuated the antinociceptive, but not hypothermic, effects of buspirone (1-5 mg/kg, i.p.). Administration of the phenylethanolamine-N-methyltransferase (PNMT) inhibitor, dichloromethylbenzylamine (DCMB: 25 mg/kg, i.p.) reduced basal and buspirone-elevated plasma EPI, but not CST levels. This treatment did not affect buspirone-induced hypothermia, while significantly reducing buspirone antinociception. Pretreatment with the CST synthesis inhibitor, aminoglutethemide (AG: 2 x 25 mg/kg, i.p.), reduced plasma CST levels while not significantly affecting EPI. AG pretreatment did not alter the hypothermic effects of buspirone, but attenuated antinociception produced by the highest buspirone dose. The AG-induced reductions of buspirone antinociception were less than those effects produced by DCMB treatment. These data suggest that buspirone-induced antinociception may be a non-opioid, adrenally mediated co- and/or epi-phenomenon to core hypothermia evoked by 5-HT1A receptor agonism.

Adrenalectomy↗
PubMed1990

[Reproductive and developmental toxicity studies of buspirone hydrochloride (I)--Oral administration to rats during the period of fetal organogenesis].

Buspirone hydrochloride (buspirone), an anxiolytic drug, was administered orally to pregnant Crj: CD (Sprague-Dawley) rats from day 7 through 17 of gestation at dose levels of 2, 12 and 75 mg/kg/day. The summarized results obtained are as follows: 1. Decreased activity was observed for F0 dams at buspirone 75 mg/kg. Further, the suppression of maternal body weight gains accompanied by the reduction of food consumption was shown during the administration period at the same dose level. 2. Liver weights were increased in F0 dams at term at buspirone 12 mg/kg and higher. Besides, brain, pituitary, adrenal and ovarian weights were increased in F0 dams at term at buspirone 75 mg/kg. 3. Buspirone 75 mg/kg brought the inhibition of fetal growth followed by the lowered values in fetal weights, crown-rump distances and tail lengths. Furthermore, the elevated incidence of skeletal abnormalities such as nodular and wavy ribs and unossified 5th and 6th sternum , as well as retarded ossification of cervical vertebrae, forelimbs and hindlimbs were also noted in this dose level. Also, the retarded ossification was observed at 12 mg/kg. 4. Buspirone failed to affect the parturition of F0 dams. 5. Buspirone did not function the viability of newborns (F1), and postnatal differentiations, learning ability, motility, motor activity or emotional development in F1 animals. 6. Body weight gains were depressed in female F1 rats from 4 to 9 weeks of age and food consumption was decreased in male F1 rats from 6 to 8 weeks of age at buspirone 75 mg/kg. 7. Buspirone 75 mg/kg produced suppressions of brain weights at 10 weeks of age in male and female F1 rats and lung weights at weaning in male F1 rats. Spleen weights were increased in female F1 rats at 10 weeks of age at the same dose level. However, buspirone failed to affect their reproductive ability. 8. F2 neonates derived from F1 rats whose dams had ever received buspirone during the period of fetal organogenesis showed no changes in observation items at birth. Based on these results, the no-effect dose level of oral buspirone under the present experimental condition was estimated to be 2 mg/kg/day against dams and their offspring.

Abnormalities, Drug-Induced↗
PubMed1990

[Reproductive and developmental toxicity studies of buspirone hydrochloride (II)--Oral administration to rats during perinatal and lactation periods].

Buspirone hydrochloride (buspirone), an anxiolytic drug, was administered orally to pregnant Crj: CD (Sprague-Dawley) rats from day 17 of gestation through day 20 of postpartum at dose levels of 2, 12 and 75 mg/kg/day. The summarized results obtained are as follows: 1. Decreased activity was observed for F0 dams at buspirone 75 mg/kg. Further, the suppression of maternal body weight gains accompanied by the reduction of food consumption was shown during the administration period at buspirone 12 mg/kg and higher. 2. Brain and adrenal weights were increased in F0 dams at buspirone 12 mg/kg and higher. Besides, lung and pituitary weights were augmented in F0 dams at buspirone 75 mg/kg. 3. Buspirone 75 mg/kg brought the increased number of stillbirths in F1 neonates. 4. Buspirone 75 mg/kg lowered the viability of newborns (F1) on postnatal day 3 and prolonged the days required for pinnae detachment, presence of abdominal hair and eye opening in offspring (F1), but failed to function their learning ability, motility, motor activity or emotional development. 5. Body weight gains were depressed in both male and female F1 rats at buspirone 12 mg/kg and higher. Food consumption was also decreased in both sexes at the same dose levels. 6. Heart weights were decreased in female F1 rats after mating at buspirone 12 mg/kg and higher. Further, buspirone 75 mg/kg brought a suppression of brain weights at 10 weeks of age in male and female F1 rats, but failed to affect their reproductive ability. 7. F2 neonates derived from F1 rats whose dams had ever received buspirone during the perinatal and lactation periods showed no changes in observation items at birth. Based on these results, the no-effect dose level of oral buspirone under the present experimental condition was estimated to be 2 mg/kg/day against dams and their offspring.

Abnormalities, Drug-Induced↗
PubMed1989

Buspirone in the treatment of alcoholic patients.

Buspirone is a unique anxiolytic drug with established efficacy in the treatment of anxiety. In animals, buspirone has been shown to alter drinking preference from alcohol to water. The following study was conducted to evaluate the behavioral effects of buspirone in patients meeting the Diagnostic and Statistical Manual of Mental Disorders (3rd ed.; DSM-III) criteria of alcohol abuse. These patients were motivated to reduce or stop drinking, though none were abstinent at baseline. Buspirone was compared with placebo in a double-blind, 8-week trial in 50 outpatients with mild to moderate alcohol abuse. Patients were assessed at baseline and at end point using the following psychometric and alcohol behavior measures: Drinking Behavior Interview (DBI), Alcohol Craving Scale, the Hamilton Anxiety (HAM-A) Rating Scale, the Hamilton Depression (HAM-D) Rating Scale, and the Physician Questionnaire. Dosage was initiated at 5 mg buspirone 3 times a day (15 mg/day), with a flexible regimen to a maximum of 30 mg/day. The mean daily dose was 20.5 mg buspirone, which is comparable to the anxiolytic dose. Efficacy measures were available for 45 patients (24 buspirone, 21 placebo). The treatment discontinuation rate was markedly lower (p = 0.002) on buspirone; 12 placebo patients and 2 buspirone patients discontinued due to lack of effect (p = 0.001). No patients discontinued due to adverse effect. Buspirone reduced alcohol craving by 40% (p = 0.001), in association with reduced HAM-A and HAM-D scores (p = 0.006) and improved the physician's assessment of global psychopathology. Buspirone treatment was also associated with a 57% decrease in DBI scores; statistical comparison of the DBI data with placebo was precluded by the high discontinuation rate in the placebo group. While these results should be interpreted with caution due to the limited sample size and high placebo discontinuation rate, the findings suggest that further evaluation of buspirone in the management of alcoholism, especially abstinent alcoholics, is warranted.

Adult↗
PubMed1986

Behavioral studies with anxiolytic drugs. III. Antipunishment actions of buspirone in the pigeon do not involve benzodiazepine receptor mechanisms.

Buspirone, a clinically effective anxiolytic, has not shown robust effects consistently in procedures used traditionally with rodents and nonhuman primates to evaluate potential antianxiety activity. When key pecking by pigeons was maintained by food and was punished alternately under one component of a multiple schedule by the presentation of electric shock (conflict procedure), buspirone (0.03-10.0 mg/kg i.m.) produced increases in punished responding that were up to 30 times those of the control response rate. These doses did not affect or decreased unpunished responding. A buspirone analog, MJ 13805 (gepirone) produced effects similar to buspirone, although unpunished responding was slightly more sensitive to the rate-decreasing effects of MJ 13805 than to those of buspirone. A metabolite of buspirone, 1-pyrimidinyl piperazine (1-PP; MJ 13653), did not affect key pecking across a wide dose range (0.01-3.0 mg/kg i.m.), although slight decreases in both punished and unpunished responding occurred at the highest dose. Increases in punished responding with buspirone were not affected by the benzodiazepine receptor antagonist Ro 15-1788 (0.01-0.1 mg/kg i.m.). [3H]Diazepam binding to pigeon cerebrum or cerebellum in vivo was not altered by buspirone, or did buspirone, MJ 13805, or 1-pyrimidinyl piperazine displace [3H]flunitrazepam binding in vitro at pharmacologically relevant concentrations. These findings confirm previous work demonstrating marked rate-increasing effects of buspirone on punished responding in the pigeon, extend such effects to the buspirone analog MJ 13805 and indicate that the effects of buspirone are not mediated through the benzodiazepine receptor complex.

Animals↗
PubMed1990

Effects of systemically administered monoamine reuptake blocking agents on patterns of buspirone-induced analgesia in rats.

We have recently shown the serotonin 5-HT1A receptor agonist buspirone to produce analgesia in several pain tests in rats. As a 5-HT1A agonist, buspirone may change serotonergic (5-HT) tone to alter the balance of central monoaminergic (MA) systems that function in analgesia. MA-reuptake blocking drugs have been shown to produce analgesia, both when given alone and in combination with a variety of other agents, presumably via their action upon MA neurochemistry. The present study was undertaken to examine the effect of systemic administration of the 5-HT-reuptake blocker amitriptyline (AMI: 10 mg/kg), NE-reuptake blocker desipramine (DMI: 10 mg/kg) or DA-reuptake blocker GBR-12909 (7.5 mg/kg) on patterns of analgesia produced by buspirone (1-5 mg/kg) in thermal and mechanical pain tests in rats. Neither reuptake blocking agents or buspirone, when administered alone or in combination, produced overt changes in motor activity at the doses tested. AMI alone was not analgesic in either thermal or mechanical pain tests. In both assays, AMI reduced the analgesic action of buspirone, with greater effects seen in the thermal test. When administered alone, DMI produced significant analgesia against thermal and mechanical pain. DMI significantly attenuated the analgesic action of all doses of buspirone in both pain tests. Alone, GBR-12909 did not affect nociception in thermal or mechanical tests. GBR-12909 decreased buspirone-induced analgesia at all doses in the thermal test, while having no effect on buspirone-induced analgesia against mechanical pain. These results demonstrate that facilitation of 5-HT, NE and DA function with reuptake blocking drugs did not enhance the analgesic action of buspirone. These data indicate against the adjuvant use of reuptake blocking compounds and buspirone as analgesics. Furthermore, such findings may suggest other possible non-MA substrates of buspirone-induced analgesia.

Amitriptyline↗
PubMed1991

Behavioral effects of chronic buspirone administration in the pigeon: comparison to midazolam.

The effects of acute and chronic administration of buspirone and midazolam were examined in White Carneau pigeons (N = 5) responding under a fixed-ratio 30 (FR 30) schedule of food presentation. Each drug was studied in all pigeons. For three pigeons, buspirone was studied before midazolam, while the order was reversed for the other two subjects. For each drug, a dose-response curve was determined before (prechronic) and two weeks after (postchronic) discontinuation of chronic administration. Prior to chronic drug administration, buspirone (0.3-5.6 mg/kg) and midazolam (0.1-3.0 mg/kg) decreased response rates in all subjects, in a dose-dependent manner. Midazolam was more potent than buspirone; midazolam's ED50 (95% C.I.) was 0.53 (0.41-0.69) mg/kg compared to 2.55 (1.48-4.41) mg/kg for buspirone. For each subject, the lowest dose that decreased responding by at least 50% was administered daily, immediately before the session, for up to 6 weeks. At the lowest daily dose of buspirone, complete recovery of baseline rates was observed in 3 pigeons. However, when the buspirone dose was increased, responding remained below control rates in all but one pigeon. During chronic midazolam administration, tolerance developed to the rate-decreasing effects of midazolam in 4 subjects. When saline was substituted for buspirone or midazolam, suppressed responding returned to predrug rates in all subjects. When the dose-response curves were redetermined, the postchronic ED50 for buspirone was 3.79 (2.10-6.82) mg/kg, which was not significantly different from the prechronic ED50, suggesting that tolerance did not develop to buspirone's rate-decreasing effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Pharmacodynamic effects of buspirone and clobazam.

1. The pharmacodynamic effects of buspirone and clobazam were compared in two volunteer studies. Acute doses of buspirone 5 mg, 10 mg and clobazam 10 mg were contrasted with placebo and a verum (lorazepam 1 mg), in a repeated measures design with 10 subjects assessed on a battery of psychometric tests at 1.5, 3.5, and 5.5 h post dose. For the combined results clobazam and the lower dose of buspirone (5 mg) were significantly contrasted with lorazepam on measures of subjective sedation, memory and choice reaction time (CRT). The higher dose of buspirone was not statistically different from lorazepam for all measures except memory; whilst contrasting significantly with placebo and clobazam on movement and total reaction time components respectively. Though failing to achieve significance, a similar trend was seen for critical flicker fusion (CFF) with buspirone 10 mg and lorazepam producing the lowest scores indicative of increased sedation. 2. Repeated doses of buspirone 5 mg twice daily, clobazam 10 mg twice daily, or placebo twice daily for 8 consecutive days were compared on the same battery of psychometric tests in a repeated measures design. Nine subjects were assessed on days 1, 3, and 8 of the study. Overall, memory performance significantly decreased with buspirone 5 mg in contrast to both clobazam and placebo whilst the opposite trend was seen with CFF. Clobazam significantly improved TRT in contrast to both placebo and buspirone. 3. These results indicate improved reaction time and memory performance with repeated dosing of clobazam in contrast to buspirone. Impairment following acute administration of buspirone appears limited to the higher (10 mg) dose.

Adult↗
PubMed1990

Buspirone in the management of major depression: a placebo-controlled comparison.

One hundred forty outpatients with major depression were admitted to an 8-week, placebo-controlled, double-blind study of buspirone. Entry criteria included a Hamilton Rating Scale for Depression (25-item [HAM-D]) score of greater than or equal to 18 and a Hamilton Rating Scale for Anxiety (HAM-A), score of greater than or equal to 18. A flexible dose schedule ranging from 5-90 mg/day was employed. The mean dose of buspirone was 41-54 mg/day from Week 2 to the end of the study. Sixty-four percent of buspirone patients and 50% of placebo patients were melancholic; 64% of buspirone patients and 74% of placebo patients discontinued treatment before the end of the study. Extender data analysis showed that buspirone patients had significant (p less than .05) HAM-D score reductions compared with the placebo group at Weeks 2, 3, 4, and 6. The HAM-D retardation factor trended toward significance over placebo at Weeks 3, 4, and 6. HAM-D change scores for the subgroup of melancholic patients taking buspirone were significantly (p less than .02) better than those of the placebo-treated melancholic subjects at Weeks 2, 3, 4, and 6. Most other efficacy parameters also favored the buspirone-treated group over the placebo-treated group. The most common adverse experiences for the buspirone group were CNS effects (74% in the buspirone group vs. 21% in the placebo group) and gastrointestinal effects (55% in the buspirone group vs. 37% in the placebo group). Side effects consisted of dizziness, light-headedness, nausea, and headache. No serious or unexpected adverse effects occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1985

Comparative chronic effects of buspirone or neuroleptics on rat brain dopaminergic neurotransmission.

Buspirone is a novel anti-anxiety drug which has neither a benzodiazepine structure nor any other benzodiazepine-like properties. Since buspirone is known to block dopamine autoreceptors and increase dopamine metabolism, it was compared to classical antipsychotic drugs for subchronic and chronic effects on dopaminergic function. When continuously infused into rats at 1.0 mg/kg/day s.c. for 2 weeks there was a small diminution of striatal dopamine metabolism response to acute injection of buspirone, but haloperidol produced a normal increase in DOPAC concentrations. In contrast, infusion of 0.3 mg/kg/day of haloperidol caused a marked subsensitivity to both acute buspirone and haloperidol challenge. The data from 3 months of treatment with buspirone or trifluoperazine (3.0 or 1.0 mg/kg/day, respectively) added to the rats' drinking water yielded similar results. Also, there was no alteration of dopamine autoreceptor sensitivity or postsynaptic D2 receptor sensitivity in 3 month buspirone treated rats. Three months of trifluoperazine produced a 45% increase in striatal binding of 3H-spiperone, which was reversed by simultaneous administration of buspirone during the final 2 weeks of trifluoperazine treatment. These data indicate that buspirone in moderate doses, such as used for treating anxiety, should be free of extrapyramidal side-effects. The modulation of neuroleptic-induced increased D2 receptor binding reinforces the hypothesis that buspirone has a modulatory effect at an unknown site within the extrapyramidal system.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1986

Buspirone: review of its pharmacology and current perspectives on its mechanism of action.

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.

Animals↗
PubMed1985

Pharmacological and clinical effects of buspirone.

Clinical trials have demonstrated that buspirone (BuSpar) is effective in the treatment of anxiety with efficacy and dosage comparable to diazepam or chlorazepate. Buspirone has a unique structure and a pharmacologic profile which distinguishes it from the benzodiazepines. Because it lacks the anticonvulsant, sedative, and muscle-relaxant properties associated with other anxiolytics, buspirone has been termed "anxioselective." Animal studies suggest that it lacks potential for abuse, and this finding is supported by clinical investigations. Further preclinical work supports the contention that buspirone lacks liability to produce physical dependence or to significantly interact with central nervous system depressants such as ethanol. Moreover, biochemical investigations have not identified any direct interaction of buspirone with the benzodiazepine-gamma-aminobutyric acid-chloride ionophore complex. Pharmacologic studies on the molecular level indicate that buspirone interacts with dopamine and serotonin receptors. Recent behavioral, electrophysiological, and biochemical studies have clearly demonstrated that early hypotheses that buspirone might be considered a neuroleptic are no longer tenable. Recent evidence indicates that other neurotransmitter systems (serotonin, norepinephrine, acetylcholine) mediate buspirone's effects. It is hoped that future studies can define the mechanism by which buspirone alleviates the clinical manifestations of anxiety.

Animals↗
PubMed1986

Interaction of buspirone and dopaminergic agents on punished behavior of pigeons.

The non-benzodiazepine anxiolytic buspirone was studied alone and in combination with either haloperidol or apomorphine. Drug effects were evaluated under a baseline of punished and unpunished keypeck responses of pigeons; every 30th response produced food (no punishment) in the presence of a white keylight and, when the keylight was red in alternate 3 min periods, every 30th response produced both food and a brief electric shock (punishment). Buspirone (0.03-3 mg/kg, IM) increased the low rates of punished responding to a maximum of 1000% of control at doses of 0.1-1 mg/kg. Unpunished responding was only marginally affected at lower doses and dose-dependent decreases were obtained from 1 to 10 mg/kg. Although less potent, chlordiazepoxide (1-100 mg/kg IM) produced effects which were similar to those of buspirone, a finding which contrasts with the greater efficacy of benzodiazepines for increasing punished behavior in mammals. Dose-effect functions for buspirone were unchanged by haloperidol administration (0.01 and 0.03 mg/kg, IM, 5 min prior) or by concurrent treatment with a behaviorally-ineffective dose of apomorphine (0.003 mg/kg, IM). Rate-decreasing doses of apomorphine (0.01-0.1 mg/kg) reversed the increases in punished responding produced by lower doses of buspirone (0.03 and 0.1 mg/kg) and the apomorphine-induced decreases in unpunished responding were antagonized by buspirone at doses which had little affect when given alone. The ability of buspirone to reverse the rate-decreasing effects of apomorphine on unpunished responding suggests that buspirone does exhibit dopaminergic antagonist properties in vivo. However, effects of buspirone on punished responding of pigeons do not appear to be due to dopaminergic mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Role of alpha-adrenoceptors in the effects of buspirone and 5-carboxamidotryptamine in rabbit isolated thoracic aorta.

1. The role of alpha-adrenoceptors in the vascular effects of buspirone (BUS) and 5-carboxamidotryptamine (5-CT) was investigated in rabbit thoracic aorta. 2. Buspirone produced a concentration-dependent contraction. The non-selective 5-HT1 and 5-HT2-receptor antagonist methysergide and the 5-HT2 receptor antagonist ketanserin did not alter the contractile effect of buspirone. However, the competitive antagonist of alpha 1-adrenoceptors, prazosin, shifted the concentration-response curve of buspirone to the right without changing the maximal response. 3. Benextramine tetrahydrochloride monohydrate (BHC), a noncompetitive antagonist of alpha 1-adrenoceptors, inhibited the contraction induced by buspirone in a noncompetitive manner. After pretreatment with two different concentrations of BHC, the estimated apparent dissociation constants of buspirone were found to be identical. 4. In addition, buspirone antagonized the concentration-response curve of phenylephrine again showing a similar dissociation constant, suggesting a partial agonistic action of buspirone at the level of alpha 1-adrenoceptors. 5. The concentration-response curve of 5-HT showed two components in the thoracic aorta obtained from reserpine treated and untreated animals as verified by different pD2 values. The second component was observed with relatively higher concentrations of 5-CT and could be blocked by prazosin or BHC. Neither of these compounds altered the first component. After Pretreatment with BHC, the first component of 5-CT was competitively antagonized by methysergide and ketanserin, having pA2 values of 8.81 and 9.1 respectively. 6. These results suggest that the contraction induced by buspirone is mainly mediated by alpha 1-adrenoceptors, while the higher concentrations of 5-CT caused contraction via alpha 1-adrenoceptor stimulation in addition to its 5-HT2 agonistic effect.

Adrenergic alpha-Antagonists↗
PubMed1992

A double-blind study of adjuvant buspirone hydrochloride in clomipramine-treated patients with obsessive-compulsive disorder.

In this study, 14 patients with obsessive-compulsive disorder (OCD) who had received at least 3 months of treatment with clomipramine were treated with the anxiolytic agent buspirone in a 10-week, double-blind study. Before the addition of buspirone, these patients as a group had shown a partial but incomplete reduction (averaging 28%) in OCD symptoms during clomipramine treatment alone. Because buspirone has been reported to be efficacious as a sole agent and as an adjunct agent in combination with fluoxetine in patients with OCD, we were interested in assessing whether buspirone added to clomipramine treatment would be associated with further significant reductions in OCD or depressive symptoms. Although adjuvant buspirone treatment was well tolerated in most subjects, mean OCD and depressive symptoms, as evaluated by standardized rating scales, did not significantly change from baseline scores achieved on clomipramine treatment alone, either after the addition of placebo for 2 weeks or buspirone (57 +/- 7 mg/day) for an additional 10 weeks. However on an individual basis, 4 (29%) of the 14 patients did have an additional 25% reduction in OCD symptoms after adjuvant buspirone treatment. This double-blind study suggests that adjunctive buspirone therapy is not generally associated with significant further clinical improvement in OCD or depressive symptoms compared with clomipramine monotherapy, but that there may be a subgroup of patients who do benefit from adjuvant buspirone therapy.

Adult↗
PubMed1989

Evidence that central 5-hydroxytryptaminergic neurones are involved in the anxiolytic activity of buspirone.

1. A two-compartment exploratory test was used to assess the role of central 5-hydroxytryptaminergic neurones in the anxiolytic activity of buspirone in rats. 2. Buspirone 0.1 mg kg-1, administered subcutaneously 15 min before testing, significantly increased black-white transitions (BWT) in control rats but had no effect in animals injected intracerebroventricularly one week before with 150 micrograms 5,7-dihydroxytryptamine (in 20 microliters). 3. Infusion of buspirone in the median raphe (but not in the dorsal raphe) significantly enhanced BWT, at doses from 1 micrograms to 10 micrograms (in 0.5 microliters). Buspirone 5 and 10 micrograms, but not 1 microgram, administered in the median raphe, significantly enhanced motor activity of rats during the first 10 min of testing in the activity cages. 4. The effect on BWT of 5 micrograms buspirone in the median raphe was completely antagonized in animals which had received either 5,7-dihydroxytryptamine intraventricularly, 150 micrograms (in 20 microliters), one week before or an infusion of 0.1 microgram (in 0.5 microliter) (-)-propranolol in the same area 5 min before. (-)-Propranolol infused in the median raphe did not modify the effect of buspirone on locomotion. 5. Infusion of 5 micrograms buspirone (in 0.5 microliter) in the median raphe significantly enhanced punished responses in a conflict test with no effect on unpunished responding. Buspirone infused in the dorsal raphe had no effect on punished or unpunished responding over a wide dose range. 6. The results indicate that at the relatively low dose used in the present study buspirone produces an anxiolytic effect by acting on central 5-hydroxytryptaminergic neurones. It is likely that activation of 5-hydroxytryptamine1A-receptors in the median raphe is involved.

8-Hydroxy-2-(di-n-propylamino)tetralin↗