Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Buspirone”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 145 records · Page 8Linked to original sources
PubMed2003

Effects of the serotonergic anxiolytic buspirone on plasma glucose and glucose-induced hyperglycemia in mice.

Effects of the serotonergic anxiolytic buspirone on plasma glucose and glucose-induced hyperglycemia were studied in mice. Buspirone did not affect plasma glucose levels of non-fasted mice, while it increased serum insulin levels. In fasted mice, buspirone significantly reduced glucose-induced hyperglycemia and enhanced insulin release elicited by glucose. This suggests that buspirone enhances insulin release, resulting in inhibition of glucose-induced hyperglycemia. The major metabolite of buspirone, 1-(2-pyrimidinyl)piperazine (1-PP) increased serum insulin levels and induced a slight hypoglycemia in non-fasted mice. 1-PP decreases glucose-induced hyperglycemia and amplifies insulin release elicited by glucose in fasted mice. Since buspirone is mainly metabolized to 1-PP and formation of 1-PP occurs quickly, the inhibitory effect of buspirone on glucose-induced hyperglycemia is likely mediated by 1-PP.

Animals↗
PubMed1999

Efficacy, safety, and tolerability of venlafaxine extended release and buspirone in outpatients with generalized anxiety disorder.

BACKGROUND: The objective of this randomized, double-blind study was to compare the efficacy and safety of venlafaxine extended release (XR) and buspirone in outpatients with generalized anxiety disorder (GAD) but without concomitant major depressive disorder. METHOD: Male and female outpatients at least 18 years old who met the DSM-IV criteria for GAD and had scores of 18 or higher on the Hamilton Rating Scale for Anxiety (HAM-A) were randomly assigned to treatment with either venlafaxine XR (75 or 150 mg/day), buspirone (30 mg/day in 3 divided doses), or placebo for 8 weeks. The primary efficacy variables were changes in anxiety as determined by final on-therapy HAM-A total and psychic anxiety scores and Clinical Global Impressions scale (CGI) scores. Other key efficacy variables were HAM-A anxious mood and tension scores and the anxiety subscale scores of the patient-rated Hospital Anxiety and Depression scale (HAD). RESULTS: The efficacy analysis included 365 patients and the safety analysis, 405. At week 8, adjusted mean HAM-A psychic anxiety, anxious mood, and tension scores were significantly lower for venlafaxine XR-treated patients than for placebo-treated patients. On the HAD anxiety subscale, venlafaxine XR, 75 or 150 mg/day, was significantly more efficacious than placebo at all time points except weeks 1 (both dosages) and 2 (150-mg/day dosage only) and significantly more efficacious than buspirone at all time points except week 1. On the CGI-Improvement scale, scores for venlafaxine XR (both dosages) and buspirone were numerically superior to those for placebo at all time points, and statistical significance was observed at weeks 3, 4, 6, and 8 for venlafaxine XR and at weeks 6 and 8 for buspirone. The adverse events were not essentially different between treatment groups. CONCLUSION: Venlafaxine XR is an effective, safe, and well-tolerated once-daily anxiolytic agent in patients with GAD without comorbid major depressive disorder. This agent was significantly superior to buspirone on the HAD anxiety subscale. Buspirone demonstrated statistical significance versus placebo on a measure of anxiolytic response.

Ambulatory Care↗
PubMed2001

Patients with severe depression may benefit from buspirone augmentation of selective serotonin reuptake inhibitors: results from a placebo-controlled, randomized, double-blind, placebo wash-in study.

BACKGROUND: Although case reports and open studies have reported augmentation with buspirone to be beneficial in the treatment of depression refractory to treatment with a selective serotonin reuptake inhibitor (SSRI), a recently published randomized, placebo-controlled, double-blind study failed to show superiority of buspirone over placebo in this respect. METHOD: One hundred two outpatients who fulfilled DSM-IV criteria for a major depressive episode and who had failed to respond to a minimum of 6 weeks of treatment with either fluoxetine or citalopram were included in this double-blind, randomized, placebo-controlled study. After a single-blind placebo wash-in period of 2 weeks while continuing their SSRI, the patients were randomly assigned to adjunctive treatment with either buspirone, 10 to 30 mg b.i.d., or placebo for 6 weeks. Patients were assessed using the Montgomery-Asberg Depression Rating Scale (MADRS), the Clinical Global Impressions scale (CGI), and visual analogue scales. RESULTS: After the first week of double-blind treatment, there was a significantly greater reduction in MADRS score (p = .034) in the buspirone group as compared with placebo. At endpoint, there was no significant difference between treatment groups as a whole, although patients with initially high MADRS scores (> 30) showed a significantly greater reduction in MADRS score (p = .026) in the buspirone group as compared with placebo. CONCLUSION: Patients with severe depressive symptoms may benefit from augmentation with buspirone. It cannot be excluded that augmentation with buspirone may speed up the antidepressive response of patients refractory to treatment with fluoxetine or citalopram.

Adult↗
PubMed1992

Comparative drug effects and abuse liability of lorazepam, buspirone, and secobarbital in nondependent subjects.

The pharmacologic effects of lorazepam (2 mg), buspirone (20 mg, 10 mg), secobarbital (100 mg), and placebo were compared in 15 male, experienced, intermittent nontherapeutic drug users. All drugs produced a "drug effect," however, buspirone 20 mg was significantly less liked than were lorazepam, secobarbital, or buspirone 10 mg (p less than .05) but not placebo. Lorazepam was liked better than were other drugs only at 1 hour and only compared with buspirone 20 and placebo. Compared with other drugs, lorazepam drug effects were greater and resulted in more prolonged impairment of a motor tracking task, standing steadiness, and memory. Buspirone 20 mg significantly impaired memory at 1 hour compared with placebo. Subjects were more likely to identify buspirone as unfamiliar. Because buspirone 20 mg was less liked than were other drugs, dose escalation as part of drug abuse is not likely to occur. Lorazepam also was not particularly liked and was not different from placebo on most subjective abuse-relevant measures.

Adult↗
PubMed1989

Effects of buspirone and its metabolite, 1-(2-pyrimidinyl)piperazine, on brain monoamines and their metabolites in rats.

Buspirone, an anxiolytic drug with selective affinity for the 5-HT-1A subtype of serotonin receptors, caused a dose-related decrease in 5-hydroxyindole acetic acid (5-HIAA) concentration in rat hypothalamus after doses of 1 to 10 mg/kg s.c. The decrease in 5-HIAA concentration after a 3 mg/kg s.c. dose of buspirone persisted at 4 hr but not at 7 hr. The decrease was due apparently to a reduced turnover of serotonin; the accumulation of 5-hydroxytryptophan after decarboxylase inhibition was also suppressed by buspirone, not only in hypothalamus but also in brain stem, hippocampus and striatum. 1-(2-Pyrimidinyl)-piperazine (1-PP), a major metabolite of buspirone, did not affect hypothalamic 5-HIAA concentration at doses up to 10 mg/kg s.c. Both buspirone and 1-PP increased hypothalamic concentrations of 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) sulfate, the norepinephrine metabolite, the effect being more pronounced with 1-PP but occurring after doses as low as 0.3 mg/kg s.c. with each compound. The increase in MHPG sulfate concentration persisted for at least 4 hr after a 3 mg/kg s.c. dose of each compound. The increase in MHPG sulfate produced by buspirone may have been due partly to 5-HT-1A receptor activation, inasmuch as other serotonin agonists have been found to cause a similar increase. 1-PP is reported to lack affinity for 5-HT-1A receptors so its elevation of MHPG sulfate concentration may have resulted from alpha-2 receptor blockade. The increase in MHPG sulfate concentration after buspirone injection may have been due at least partly to formation of the metabolite, 1-PP.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1987

A comparison of buspirone and placebo in relieving benzodiazepine withdrawal symptoms.

Buspirone is a new antianxiety compound of a totally new type which may avoid the dependence problems of its predecessors. This study was designed to evaluate any possible cross-tolerance to the benzodiazepines. Twenty-four outpatients on long-term therapeutic dose benzodiazepine treatment, who wished to discontinue treatment, were allocated randomly to placebo substitution or buspirone substitution and then withdrawal over a total of 10 weeks. Assessments were made at weekly intervals. Of the 24 patients entered into the trial, 13 received buspirone and 11 placebo. Only five of the buspirone and six of the placebo patients successfully completed withdrawal. Some anxiolytic action of buspirone was detected, but it was insufficient to materially assist the withdrawal. No evidence was found that buspirone was cross-tolerant to the benzodiazepines. It was concluded that buspirone does not help benzodiazepine withdrawal and does not suppress benzodiazepine withdrawal symptoms.

Adult↗
PubMed1988

Buspirone attenuates synaptic activation of hippocampal pyramidal cells.

The actions of 5-hydroxytryptamine (5-HT) and buspirone, an anxiolytic agent that displays high and selective affinity for 5-HT1A receptor sites, on synaptic activation of hippocampal CA1 pyramidal cells were studied in vitro. Whereas 5-HT application leads to a rapid hyperpolarization and decreased input resistance in pyramidal cells, buspirone has no measurable effects on membrane potential and input resistance. However, unlike 5-HT, buspirone application leads to a gradual and reversible reduction in excitatory postsynaptic potentials (EPSPs) elicited by stimulation of afferents in the stratum radiatum. Concurrent with this attenuation of the EPSP, buspirone decreases the excitability of afferent fibers in the stratum radiatum as evidenced by conduction slowing, increased refractory period, and decreased ability to generate repetitive impulses. 5-HT has no measurable effect on the afferent fibers. The attenuation of the EPSPs and the decrease in afferent fiber excitability appear to be independent of 5-HT receptors as 5-HT neither shares nor antagonizes the effects of buspirone. Thus, both 5-HT and buspirone can contribute to reduced spike activity in pyramidal cells, but they do so via different mechanisms: 5-HT hyperpolarizes pyramidal cells whereas buspirone attenuates their synaptic activation, possibly via action on the presynaptic fibers in the stratum radiatum.

Afferent Pathways↗
PubMed1998

A randomized, double-blind, placebo-controlled trial of buspirone in combination with an SSRI in patients with treatment-refractory depression.

BACKGROUND: Case reports and open studies have reported beneficial therapeutic effects of adding buspirone to a selective serotonin reuptake inhibitor (SSRI) in the management of treatment-refractory depression. This is the first placebo-controlled study to evaluate the efficacy and safety of this combination. METHOD: One hundred nineteen patients (82 women, 37 men) who fulfilled criteria for a major depressive episode according to DSM-IV and who had failed to respond to a minimum of 4 weeks (mean = 211 days) of treatment with citalopram or paroxetine were randomly assigned to 4 weeks of treatment with an SSRI plus buspirone (N = 58) or an SSRI plus placebo (N = 61). In addition, 97 patients participated in an optional open-label poststudy treatment phase with the SSRI plus buspirone for 2 weeks. The primary outcome measure was the score on the Clinical Global Impressions-Improvement (CGI-I) scale. RESULTS: A total of 50.9% of patients in the buspirone group and 46.7% in the placebo group responded after 4 weeks of treatment. The difference in response rate was not statistically significant. No statistically significant differences were found in the frequency of adverse events. At the follow-up of the open SSRI plus buspirone treatment, 69.4% of patients had responded. CONCLUSION: Adding buspirone to an SSRI is a safe and well-tolerated drug regimen. This study failed to demonstrate any difference in efficacy between buspirone or placebo augmentation of an SSRI. It could be argued, however, that the study was inconclusive due to the unusually high placebo response.

Adult↗
PubMedDate not supplied

Treatment with buspirone in a patient with autism.

This study evaluates the safety and efficacy of buspirone hydrochloride for the treatment of a patient with autism and hyperactivity disorder and determines the effect of buspirone on the number of performance tasks completed by the patient at school. A 3-week, double-blind, placebo-controlled crossover study was performed in a private physician, office-based practice. A child with autism, which was diagnosed by Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised, criteria, was studied. The child received placebo for 3 weeks and buspirone for 3 weeks; there was a 1-week interval between the 2 treatments. The outcome was measured by using Conners abbreviated parent and teacher questionnaires and by determining the number of daily performance tasks completed by the child at school. Statistical analysis was performed by linear models and standard F tests. Buspirone was found to be safe and efficacious, without side effects, for decreasing hyperactivity and increasing completed performance tasks. The beneficial effects of buspirone in helping this patient with autism in his natural daily settings suggest that buspirone may be an alternative to neuroleptic agents in the medical therapy of autism; further study in other patients is needed.

Anti-Anxiety Agents↗
PubMed1988

Buspirone: an update on a unique anxiolytic agent.

Buspirone (Buspar) is a azaspirodecanedione anxiolytic agent. Its mechanism of action is extremely complex, but current investigations indicate that its main neuropharmacologic effects are mediated by the 5-HT1A receptors. Other neuroreceptor systems could be involved, as buspirone displays some affinity for DA2 autoreceptors and 5-HT2 receptors. It has been proposed that inhibition of synthesis and release of serotonin result through the combined interactions of neuroreceptors and secondary messenger systems. This action leads to inhibition of the firing rate of 5-HT-containing neurons in the dorsal raphe. From this novel profile, that differs from that of the benzodiazepines, buspirone lacks anticonvulsant and muscle-relaxant properties, and causes only minimal sedation. The drug is rapidly absorbed after oral administration, with a mean bioavailability of 3.9%. After a single oral dose, the mean elimination half-life is 2.1 hours. Buspirone is mainly bound to albumin and alpha 1-acid glycoprotein. It is metabolized to an active metabolite 1-(2-pyrimidinyl) piperazine (1-PP). The mean elimination half-life of 1-PP is 6.1 hours. Buspirone is indicated in the treatment of generalized anxiety disorders. Its efficacy is comparable to the benzodiazepines. Its use in depression and panic disorders requires further investigation. When combined with alcohol or given alone, psychomotor impairment was not detected. Abuse, dependence, and withdrawal symptoms have not been reported. The frequency of adverse effects is low, and the most common effects are headaches, dizziness, nervousness, and lightheadness. Buspirone should be added to drug formularies and could represent a significant addition in psychopharmacology.

Anxiety↗
PubMed2002

Buspirone decreases physiological reactivity to unconditioned and conditioned aversive stimuli.

RATIONALE: Serotonergic pathways are thought to be important in mediating the effects of aversive events. OBJECTIVE: To investigate the effects of buspirone, a 5-HT(1A) partial agonist, on habituation and extinction in an aversive classical conditioning model. METHODS: Forty healthy male volunteers were randomly assigned to a single dose of buspirone (10 mg) or placebo. They filled in questionnaires of anxiety and depression at baseline and visual analogue scales of tension and anxiety before and at 60, 120 and 150 min after drug administration. Their skin conductance responses to auditory stimuli were measured on the conditioning model 2 h after drug intake. RESULTS: There were no differences between groups on depression or anxiety. Buspirone decreased the amplitude of the skin conductance response and the number of spontaneous fluctuations in both the habituation and extinction phases but had no effect on skin conductance level. Buspirone also attenuated the unconditioned response to the white noise and the response to the first tone. Visual analogue ratings of tension and anxiety decreased after buspirone. CONCLUSIONS: Buspirone decreased physiological reactivity in an aversive classical conditioning model. It had anxiolytic effects on both conditioned and unconditioned anxiety. This might be due to its multiple actions on 5-HT receptors.

Administration, Oral↗
PubMed1996

The effect of chronic fluvoxamine on hormonal and psychological responses to buspirone in normal volunteers.

We studied the effect of 3 weeks treatment with the selective serotonin reuptake inhibitor (SSRI), fluvoxamine, on hormonal and psychological responses to buspirone, a 5-HT1A receptor partial agonist which also binds to dopamine receptors, in normal male volunteers. Eleven subjects received buspirone, 30 mg, and placebo before, and in week 3 of fluvoxamine treatment (mean dose 127 mg/day). Placebo and buspirone were given in a balanced order, double-blind. Buspirone significantly elevated plasma prolactin (PRL) and growth hormone (GH) concentrations but had no significant effect on cortisol (CORT) or temperature. Significant psychological effects of lightheadedness, tiredness and difficulty thinking occurred. Fluvoxamine treatment resulted in a nearly 3-fold increase in plasma buspirone with a similar enhancement of the PRL response. In contrast the GH and psychological responses were blunted. The increased buspirone concentrations are likely to be due to inhibition of first pass liver metabolism by fluvoxamine acting on the cytochrome P-450 system. The PRL response is probably mediated by antagonism of pituitary dopamine-D2 receptors and its enhancement by fluvoxamine treatment may be a pharmacokinetic effect. The blunting of GH and psychological responses suggest that 5-HT1A receptor function is reduced by chronic fluvoxamine treatment.

Adult↗
PubMed1998

Buspirone and lorazepam in the treatment of generalized anxiety disorder in outpatients.

In this double-blind, placebo-controlled 10-week trial, the anxiolytic properties of the nonbenzodiazepine buspirone were compared with the benzodiazepine lorazepam and placebo in 125 outpatients with generalized anxiety disorder according to DSM-III. After a 3- to 7-day wash-out period, patients were allocated at random to receive orally 3 x 5 mg buspirone (n=58), 3 x 1 mg lorazepam (n=57), or placebo (n=10) over a 4-week period. The study also comprised a 2-week taper period and a 4-week placebo-control period to assess the stability of clinical improvement. The patient's clinical state was estimated on entry and at weekly intervals by general practitioners using the Hamilton Rating Scale for Anxiety (HAM-A) and Clinical Global Impression (CGI) assessment and by a self-rating scale (State Trait Anxiety Inventory X2=STAI-X2). Lorazepam treatment resulted in descriptively, but not significantly, greater improvement on the Hamilton Rating Scale for Anxiety during the whole treatment (week 0-4) and taper period (week 5, 6) than did buspirone. After treatment with active drugs had been discontinued, the 4-week placebo control period showed buspirone-treated patients to display a stability of clinical improvement, while the symptoms of lorazepam-treated patients worsened at week 7-10. Both buspirone and lorazepam were more efficacious in reducing anxiety symptoms than placebo during the treatment and taper period; however, in contrast to the active drugs (buspirone, lorazepam), patients of the placebo group showed further clinical improvement during the control period, especially in the HAM-A score, so differences between placebo and active drugs became smaller at the end of the study.

Adult↗
PubMed1983

Dopaminergic effects of buspirone, a novel anxiolytic agent.

The novel anxiolytic drug buspirone raised striatal levels of the dopamine metabolites homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC) 1 hr after oral administration. This effect was dose-dependent with a peak at 60 min. No changes were observed in the levels of 3-methoxytyramine (3MT), the extraneuronal metabolite of dopamine. Noradrenaline, serotonin and its metabolite 5-hydroxyindoleacetic acid (5HIAA) were not affected. Buspirone displaced [3H]spiroperidol from striatal binding sites, with an IC50 (1.8 x 10(-7) M), comparable to that of clozapine (IC50 = 1.4 x 10(-7) M) but considerably lower than that of haloperidol (4.7 x 10(-9) M). Buspirone was only a weak inhibitor of dopamine-stimulated adenyl cyclase. Buspirone was not active on the binding of trifluoperazine to calmodulin and did not modify calmodulin-induced activation of phosphodiesterase (PDE). Repeated administration of buspirone did not increase the number of DA receptors. These data show that, although buspirone has antidopaminergic activity, it can hardly be classified as a classic neuroleptic agent.

Animals↗
PubMed1994

Effects of buspirone on plasma prolactin and cortisol levels in major depressed and normal subjects.

The cortisol response to ipsapirone (a 5-HT1A-partial agonist that produces a dose-dependent increase in plasma cortisol secretion in man) is blunted in major depression. Buspirone is another 5-HT1A agonist that increases cortisol secretion in man. This study investigated cortisol and prolactin (PRL) responses to buspirone (30 mg orally) in 45 major depressed subjects and 28 normal controls. Buspirone administration yielded a significant increase in cortisol and PRL levels in both normal controls and depressed subjects. No differences in buspirone-induced hormone responses were found either between major depressives and normal controls or between melancholic and nonmelancholic depressives. There were no significant relationships between severity of depression and any of the hormonal responses to buspirone. PRL responses to buspirone were significantly higher in women than in men.

Adult↗
PubMed1988

Buspirone, 8-OH-DPAT and ipsapirone: effects on hippocampal cerebellar and sciatic fiber excitability.

The effects of serotonin (5-hydroxytryptamine; 5-HT), and the novel anxiolytics buspirone, 8-OH-DPAT (8-hydroxy-2-[N,N-dipropylamino]-tetralin) and ipsapirone (TVXQ 7821, 2-[4-[4-[2-pyrimidinyl]-1-piperazinyl] butyl]-1,2-benzisothiazol-3[2H]one-1,1-dioxide-hydrochloride) on fiber excitability were studied in three axon systems; hippocampal Schaffer collateral fibers, cerebellar parallel fibers, and sciatic nerves. In the hippocampus, application of buspirone, 8-OH-DPAT and ipsapirone resulted in reversible, dose-dependent reductions in the amplitude and conduction velocity of action potentials recorded from presynaptic afferent fibers. Although these agents bind to 5-HT1A receptors, 5-HT application, even at very high (1 mM) concentrations, did not alter axonal responses. This suggests that buspirone, 8-OH-DPAT and ipsapirone exert an action independent of a serotonergic mechanism. Similar effects were observed on the cerebellar parallel fibers although the cerebellum does not have an appreciable number of 5-HT1A receptors. To examine the generalized effects of these agents on nerve excitability, rat sciatic compound action potentials were studied with sucrose gap recordings. Whereas 5-HT, 8-OH-DPAT and ipsapirone had no effects even at high concentrations (1 mM), application of buspirone led to reversible decrement of the responses without appreciable change in membrane potential. These results indicate that buspirone, 8-OH-DPAT and ipsapirone have actions on the excitability of hippocampal and cerebellar neurons independent of serotonergic mechanisms. Moreover, buspirone, but not 8-OH-DPAT or ipsapirone, produces decreased sciatic nerve excitability. NS 20393

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1995

Buspirone, but not sumatriptan, induces miosis in humans: relevance for a serotoninergic pupil control.

BACKGROUND AND OBJECTIVE: Drugs that act on the serotoninergic system have been shown to influence the pupil size. However, the 5-hydroxytryptamine (5-HT) receptor type or subtype that affects pupil diameter has not been defined in humans. With a placebo-controlled, double-blind randomized design, we investigated in healthy volunteers the effect on pupil size of buspirone and sumatriptan, which mainly act on 5-HT1A- and the 5-HT1-like receptors, respectively. METHODS: The pupil area was measured by means of a videopupillometer before and after a single oral administration of placebo or of three different doses of active drugs. Heart rate and arterial blood pressure were recorded after pupil area measurement. RESULTS: Buspirone (5, 10, and 20 mg) caused a dose-dependent miosis. Sumatriptan (50, 100, and 200 mg) did not affect the pupil size. Twenty milligrams of buspirone reduced the mydriasis induced by pretreatment with homatropine eyedrops. A 20 mg dose of buspirone reduced blood pressure without change in heart rate, whereas buspirone, at doses lower than 20 mg, and sumatriptan did not affect heart rate and blood pressure. CONCLUSIONS: This study suggests that buspirone, but not sumatriptan, the selective agonist of 5-HT1-like receptors, causes miosis in humans by activation of 5-HT1A receptors, possibly located in the central nervous system where they inhibit iris sympathetic pathways. Measurement of pupil size seems to provide a valuable and sensitive index of 5-HT1A receptor function in humans.

Administration, Oral↗
PubMed1988

Blockade of alpha 2-adrenoceptors by 1-(2-pyrimidinyl)-piperazine (PmP) in vivo and its relation to the activity of buspirone.

The effect of 1-(2-pyrimidinyl)-piperazine (PmP) and the parent drug, buspirone in counteracting the behavioral and biochemical effects of clonidine were evaluated in the rat. Intraperitoneal or oral administration of PmP, buspirone and yohimbine, but not of prazosin, antagonized the slowing of gastrointestinal motility induced by subcutaneous clonidine (0.1 mg/kg). The doses that inhibited the effect of clonidine on the transit time by 50% were 0.5 mg/kg i.p. and 0.7 mg/kg p.o. for PmP, 7 mg/kg i.p. and 9 mg/kg p.o. for buspirone and 0.5 mg/kg i.p. for yohimbine. PmP (0.5 mg/kg) did not block the antitransit effect of clonidine when administered by intracerebroventricular injection. The antitransit effect of a low dose of morphine (0.05 mg/kg i.p.) was not blocked by PmP (2 mg/kg i.p.). The prolongation of the hexobarbital-induced loss of the righting reflex that occurs after clonidine (0.25 mg/kg i.p.) administration was inhibited by pretreatment with PmP (0.1-2 mg/kg p.o.) or yohimbine (1 mg/kg i.p.) but not by pretreatment with prazosin (2 mg/kg i.p.). Buspirone (1-20 mg/kg) also reduced the effect of clonidine after oral administration, with a maximal effect at 5 mg/kg, whereas the same dose administered i.v. had less effect. PmP (2 mg/kg) and buspirone (15 mg/kg) raised the levels of total 3-methoxy-4-hydroxyphenylgycol (MHPG) in rat cerebral cortex, and prevented the decrease in MHPG induced by clonidine. These findings show that buspirone, in doses at which it is active as an anxiolytic, suppresses the central and peripheral effects of clonidine. This action occurs through alpha 2-adrenoceptors and is mediated primarily by the metabolite, PmP.

Adrenergic alpha-Antagonists↗