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PubMed1986

Effect of the anxiolytic drug buspirone on prolactin and corticosterone secretion in stressed and unstressed rats.

Buspirone is an atypical anxiolytic drug that exerts its action at a receptor site other than the GABA-benzodiazepine-chloride ionophore complex. The present study examined the effect of buspirone on plasma prolactin and corticosterone levels in both control and stressed rats. In unstressed rats, buspirone produced dose-dependent increases in plasma prolactin and corticosterone levels. The minimal doses of buspirone which led to significant elevations in plasma prolactin and corticosterone levels were 1.0 and 2.0 mg/kg (IP), respectively. The effect of buspirone on both hormones was maximal 30 minutes after injection. The plasma levels of prolactin and corticosterone were significantly elevated in rats that were stressed using a conditioned fear paradigm. Buspirone produced a dose-dependent attenuation of the stress-induced increase in prolactin secretion. The stress-induced increase in corticosterone secretion was inhibited by the 0.5 mg/kg (IP) dose but not by the 2.0 mg/kg (IP) dose of buspirone, which increased corticosterone secretion both in stressed and unstressed rats. These data suggest that the effect of buspirone on plasma prolactin and corticosterone levels may be mediated by two different mechanisms of action.

Adrenal Cortex↗
PubMed2001

Buspirone and meperidine synergistically reduce the shivering threshold.

UNLABELLED: Mild hypothermia (i.e., 34 degrees C) may prove therapeutic for patients with stroke, but it usually provokes shivering. We tested the hypothesis that the combination of buspirone (a serotonin 1A partial agonist) and meperidine synergistically reduces the shivering threshold (triggering tympanic membrane temperature) to at least 34 degrees C while producing little sedation or respiratory depression. Eight volunteers each participated on four randomly-assigned days: 1) large-dose oral buspirone (60 mg); 2) large-dose IV meperidine (target plasma concentration of 0.8 microg/mL); 3) the combination of buspirone (30 mg) and meperidine (0.4 microg/mL); and 4) a control day without drugs. Core hypothermia was induced by infusion of lactated Ringer's solution at 4 degrees C. The control shivering threshold was 35.7 degrees C +/- 0.2 degrees C. The threshold was 35.0 degrees C +/- 0.8 degrees C during large-dose buspirone and 33.4 degrees C +/- 0.3 degrees C during large-dose meperidine. The threshold during the combination of the two drugs was 33.4 degrees C +/- 0.7 degrees C. There was minimal sedation on the buspirone and combination days and mild sedation on the large-dose meperidine day. End-tidal PCO2 increased approximately 10 mm Hg with meperidine alone. Buspirone alone slightly reduced the shivering threshold. The combination of small-dose buspirone and small-dose meperidine acted synergistically to reduce the shivering threshold while causing little sedation or respiratory toxicity. IMPLICATIONS: Mild hypothermia may be an effective treatment for acute stroke, but it usually triggers shivering, which could be harmful. Our results indicate that the combination of small-dose buspirone and small-dose meperidine acts synergistically to reduce the shivering threshold while causing little sedation or respiratory toxicity. This combination may facilitate the induction of therapeutic hypothermia in stroke victims.

Adult↗
PubMed1999

Determination of buspirone and 1-(2-pyrimidinyl)-piperazine (1-PP) in human plasma by capillary gas chromatography.

Two separate gas chromatographic methods for the determination of buspirone and its active metabolite, 1-(2-pyrimidinyl)-piperazine (1-PP) in human plasma are described. Both procedures involve solid-phase extraction (the packing material of the cartridges used was C8 for buspirone and a mixed-mode sorbent for 1-PP), injection of the sample into a gas chromatograph equipped with a fused-silica capillary column and a nitrogen-phosphorus detector, and analysis with temperature programming (from 220 degrees C to 285 degrees C for buspirone and from 138 degrees C to 285 degrees C for 1-PP). The coating material of the analytical column was 5% diphenyl dimethyl silicone for buspirone and 50% diphenyl dimethyl silicone for 1-PP. Zolpidem was used as an internal standard in the buspirone assay and 1-phenylpiperazine in the 1-PP assay. Recovery of buspirone and 1-PP averaged 98% and 89%, respectively, and the limit of quantification was 0.2 ng/mL for both compounds. The between-run coefficients of variation ranged from 3.2% to 9.4% and from 2.9% to 8.6% for samples spiked with three different concentrations of buspirone and 1-PP, respectively. The suitability of these assays for pharmacokinetic studies was shown by analyzing timed plasma samples from volunteers after ingestion of a single therapeutic dose of buspirone (10 mg).

Anti-Anxiety Agents↗
PubMed2005

Role of sex and sex steroids in mediating pituitary-adrenal responses to acute buspirone treatment in sheep.

Systematic characterisation of sex differences in the serotonergic modulation of the hypothalamic-pituitary-adrenal (HPA) axis may assist with our understanding of why stress-related disorders are disproportionately represented in women. In this study, we examined the acute effects of buspirone, a serotonergic 1A receptor subtype agonist, on the endocrine endpoints of adrenocorticotrophin (ACTH) and cortisol secretion in gonadectomised male and female sheep. Each sheep was treated with an acute i.v. injection containing vehicle or buspirone (0.03, 0.1 and 0.3 mg/kg) in the presence and absence of sex steroid replacement (SSR). In males, SSR treatment consisted of testosterone (2 x 200 mg s.c. pellets) and, in females, the mid-luteal phase of the oestrus cycle was simulated by treatment with oestradiol (1 cm s.c. implant) and an intravaginal controlled internal drug release device containing 0.3 g progesterone. ACTH, cortisol, testosterone and progesterone were measured in jugular blood. Basal ACTH levels were higher in males, whereas basal cortisol levels were higher in females, regardless of sex steroid status. The magnitude of the increase in ACTH and cortisol secretion following buspirone treatment was dose-dependent. There were no differences in the ACTH responses of males and females to buspirone treatment, either in the presence or absence of sex steroid replacement. However, although the cortisol response to buspirone was greater in females, there was no discernable effect of sex steroid status in addition to this sex difference on either basal or buspirone-stimulated cortisol release. We conclude that the larger basal and buspirone-stimulated cortisol response measured in females may reflect a sex difference, either in the sensitivity of the adrenal gland to ACTH or in the catecholaminergic innervation of the adrenal gland. The lack of effect of sex and sex steroids in the ACTH secretory response to buspirone may indicate that the sex differences in serotonergic modulation of the HPA axis, as reported previously by our group, were mediated via serotonergic receptor subtypes other than the 1A receptor.

Adrenocorticotropic Hormone↗
PubMed1990

The involvement of 5-hydroxytryptaminergic and dopaminergic mechanisms in the eating induced by buspirone, gepirone and ipsapirone.

1. The roles of 5-hydroxytryptamine (5-HT) and dopamine systems in mediating the increased feeding induced by buspirone, gepirone and ipsapirone were investigated. 2. All three compounds induced dose-dependent increases in food intake when administered subcutaneously to free feeding rats. Buspirone was effective over a narrower dose range than either gepirone or ipsapirone, and the maximal effect observed was smaller than the effects elicited by gepirone and ipsapirone. 3. Depletion of brain 5-HT with parachlorophenylalanine (PCPA) prevented the effects of equi-effective doses of gepirone (2.5 mg kg-1) and ipsapirone (2.5 mg kg-1), but failed to prevent buspirone (1 mg kg-1)-induced eating. Thus buspirone does not appear to interact with 5-HT systems to elicit feeding. 4. Gepirone (0.2 micrograms) and ipsapirone (0.04 and 0.2 micrograms) increased food intake when injected into the dorsal raphé nucleus (DRN), presumably by inhibiting the activity of DRN 5-hydroxytryptaminergic afferents. Buspirone (0.04-5 micrograms) was ineffective when injected into the DRN. 5. Pretreatment with haloperidol (0.1 mg kg-1, 30 min) significantly attenuated the effects of equi-effective doses of buspirone, gepirone and ipsapirone, indicating that these drugs interact with dopaminergic systems to increase feeding. 6. Previously it has been shown that each of these drugs increases striatal dopamine activity. Increased dopaminergic neurotransmission in the striatum induces a general behavioural activation, which under certain conditions facilitates feeding. It is possible that this mechanism underlies the behavioural effects of buspirone, gepirone and ipsapirone. The effects of gepirone and ipsapirone probably involve an indirect action to inhibit the activity of DRN 5-hydroxytryptaminergic afferents, whereas buspirone interacts directly with dopaminergic systems.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2002

Pharmacokinetic-pharmacodynamic modeling of buspirone and its metabolite 1-(2-pyrimidinyl)-piperazine in rats.

The objective of this investigation was to compare the in vivo potency and intrinsic activity of buspirone and its metabolite 1-(2-pyrimidinyl)-piperazine (1-PP) in rats by pharmacokinetic-pharmacodynamic modeling. Following intravenous administration of buspirone (5 or 15 mg/kg in 15 min) or 1-PP (10 mg/kg in 15 min), the time course of the concentrations in blood were determined in conjunction with the effect on body temperature. The pharmacokinetics of buspirone and 1-PP were analyzed based on a two-compartment model with metabolite formation. Differences in the pharmacokinetics of buspirone and 1-PP were observed with values for clearance of 13.1 and 8.2 ml/min and for terminal elimination half-life of 25 and 79 min, respectively. At least 26% of the administered dose of buspirone was converted into 1-PP. Complex hypothermic effects versus time profiles were observed, which were successfully analyzed on the basis of a physiological indirect response model with set-point control. Both buspirone and 1-PP behaved as partial agonists relative to R-(+)-8-hydroxy-2-(di-n-propylamino)tetralin (R-8-OH-DPAT) with values of the intrinsic activity of 0.465 and 0.312, respectively. Differences in the potency were observed with values of 17.6 and 304 ng/ml for buspirone and 1-PP, respectively. The results of this analysis show that buspirone and 1-PP behave as partial 5-hydroxytryptamine(1A) agonists in vivo and that following intravenous administration the amount of 1-PP formed is too small to contribute to the hypothermic effect.

Animals↗
PubMed2004

Buspirone raises blood pressure through activation of sympathetic nervous system and by direct activation of alpha1-adrenergic receptors after severe hemorrhage.

5-Hydroxytryptamine 1A (5-HT1A) receptor agonists reverse the hypotensive and sympathoinhibitory responses to severe hemorrhage in rats. To determine whether 5-HT1A receptor-mediated pressor responses in hypovolemic animals are due to sympathoexcitation and/or direct vasoconstriction, blood pressure (BP), heart rate (HR), and renal sympathetic nerve activity (RSNA) responses to the partial 5-HT1A receptor agonist buspirone or the more selective, full 5-HT1A receptor agonist (+)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) were compared in intact and ganglionic blocked, hemorrhaged Sprague-Dawley rats. Buspirone produced dose-dependent increases in BP (110 +/- 4(**), 86 +/- 4(**), 65 +/- 7 mm Hg), HR [369 +/- 10(**), 337 +/- 14, 277 +/- 16 beats per minute (bpm)], and RSNA (114 +/- 36(**), 34 +/- 21, -23 +/- 25% baseline for 0.2, 0.1, and 0 mg/kg; (**)p < 0.01 versus 0 mg/kg, 3 min after injection). Ganglionic blockade with hexamethonium chloride blocked the pressor effect of 9.9 microg/kg 8-OH-DPAT and attenuated, but did not block, the pressor response to 0.2 mg/kg buspirone (85 +/- 7 versus 46 +/- 6 mm Hg for buspirone + ganglionic blockade versus saline + ganglionic blockade; p < 0.01). In subsequent tests, rats treated with the selective alpha1-adrenergic receptor antagonist prazosin (25 microg/kg) continued to show extensive tachycardic (+73 +/- 26 bpm) and sympathoexcitatory (128 +/- 55% baseline) responses to 0.2 mg/kg buspirone. Ganglionic blockade combined with prazosin completely blocked all responses to buspirone. Buspirone (0.2 mg/kg) produced significant bradycardic (-89 +/- 12 bpm; p < 0.01) and sympathoinhibitory (-72 +/- 7% baseline; p < 0.01) responses in euvolemic rats 3 min after injection. It is concluded that the pressor effect of buspirone is unique to hypovolemic animals and is mediated by sympathetic activation as well as direct activation of vascular alpha1-adrenergic receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2001

Pharmacokinetics of buspirone extended-release tablets: a single-dose study.

The objective of this study is to evaluate the absorption of buspirone and its biotransformation to 1-(2-pyrimidinyl) piperazine (1-PP) from two different extended-release (ER) formulations of buspirone HCl tablets (12-hour and 24-hour in vitro release) and from a commercially available immediate-release (IR) tablet. A single dose of the 30 mg ER tablets was compared with two doses of the 15 mg IR tablet administered 12 hours apart. Eighteen healthy male subjects participated in this randomized, open-label, three-treatment crossover study. Blood samples were obtained at 22 time points from predose (0 hour) until 36 hours postdose, and plasma concentration of buspirone and 1-PP was determined by LC/tandem mass spectrometry method. The pharmacokinetic parameters AUC0-t, AUC0-infinity, Cmax, tmax, Ke, and t1/2 were calculated and statistically analyzed. The results indicated extended release of buspirone from the two test products in vivo with a 70% to 90% greater bioavailability in comparison with the IR formulation. The bioavailability of 1-PP from ER formulations appears to be equal to that from the IR formulation. Both buspirone ER tablets successfully delivered bioavailable buspirone with a reduction in peak drug and metabolite plasma levels, prolonged buspirone plasma concentrations, and decreased ratio of 1-PP to buspirone concentration with less intersubject variation when evaluated as a single-dose study in healthy human subjects.

Administration, Oral↗
PubMed1995

The effects of the serotonin1A receptor agonist buspirone on tolbutamide-induced hypoglycemia in rats.

The effects of the serotonin1A(5-HT1A) receptor agonist buspirone on hypoglycemia elicited by tolbutamide were investigated in rats. Buspirone, at doses not affecting plasma glucose levels, inhibited the hypoglycemic effects of tolbutamide. The inhibitory effects of buspirone on tolbutamide-induced hypoglycemia were antagonized by the 5-HT1A receptor antagonist pindolol. As tolbutamide is known to induce hypoglycemia by facilitating insulin release, the effects of buspirone on a tolbutamide-induced increase in serum insulin levels were also studied. However, buspirone did not affect tolbutamide-induced insulin release. Adrenodemedullation inhibited the effects of buspirone. These results suggest that buspirone inhibits tolbutamide-induced hypoglycemia mediated by the 5-HT1A receptor, and adrenaline release may be involved in the effects of buspirone.

Animals↗
PubMed1990

[Antigenicity study of buspirone hydrochloride in guinea pigs and mice].

Buspirone hydrochloride(buspirone) and buspirone-ovalbumin mixture were examined for their antigenicity in guinea pigs and mice in comparison with ovalbumin (OVA) and 2, 4-dinitrochlorobenzene (DNCB)-OVA conjugate. The results obtained were as follows: 1. When guinea pigs were sensitized with buspirone or buspirone-OVA emulsified with Freund's complete adjuvant (FCA), these animals showed negative reactions in active systemic anaphylaxis (ASA), active cutaneous anaphylaxis (ACA), passive cutaneous anaphylaxis (PCA), passive hemagglutination (PHA) and Schultz-Dale test. 2. When mice were sensitized with buspirone or buspirone-OVA adsorbed to alum, these animals revealed a negative reaction in PCA using rats. 3. As positive controls, guinea pigs were sensitized with OVA or DNCB-OVA emulsified with FCA, and mice with OVA or DNCB-OVA adsorbed to alum. As a result, these animals disclosed positive reactions in ASA, ACA, PCA, PHA and Schultz-Dale test. As shown above, buspirone was considered to possess neither antigenic nor haptenic properties.

Anaphylaxis↗
PubMed1986

Buspirone. A preliminary review of its pharmacological properties and therapeutic efficacy as an anxiolytic.

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.

Animals↗
PubMed1997

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

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 design. Thirty social phobic patients (DSM-IV) were treated with either buspirone 30 mg daily or placebo. Efficacy of treatment was measured using the Social Phobia Scale (subscores anxiety and avoidance) and the Hamilton Rating Scale for Anxiety. RESULTS: Taking a reduction of 50% or more on the Social Phobia Scale as a criterion for clinically relevant improvement, only 1 patient on buspirone and 1 on placebo were classified as responder to treatment. A subjective and clinically relevant improvement was reported by 4 patients (27%) on buspirone and 2 patients (13%) on placebo. There were no statistically significant differences between buspirone and placebo on any of the outcome measures. Generally speaking, buspirone was well tolerated. CONCLUSION: The results of the study do not support the results of open studies, in which a reduction of social anxiety and social avoidance was reported in patients with social phobia treated with buspirone.

Buspirone↗
PubMed1987

A comparison of buspirone, diazepam, and placebo in patients with chronic anxiety states.

Buspirone is an antianxiety compound that has been extensively evaluated in clinical trials: it has proved superior to placebo and comparable to diazepam in the treatment of patients with generalized anxiety disorder. In this study, 33 outpatients with generalized anxiety disorder were entered into a crossover study of 3 weeks each of placebo, buspirone 10 to 30 mg daily, and diazepam 10 to 30 mg daily. Psychiatrist and patient ratings were made, together with psychological tests and EEG and skin conductance measures before and after each treatment. Of the nine dropouts, six were on buspirone at the time of dropout. For the remaining 24 patients, the mean daily doses attained of buspirone and diazepam were both 20 mg. On most clinical ratings diazepam was superior to buspirone and placebo, which did not differ. Diazepam produced minor psychomotor changes and the expected major effects on the EEG. Buspirone was without effect. Side effects on buspirone were mainly nausea and giddiness and on diazepam, drowsiness. The lack of efficacy of buspirone is discussed in terms of the previous benzodiazepine exposure--23/24 patients had had previous exposure and only 10 were able to tolerate a pretrial placebo washout period. The implications are considerable for the introduction of any new antianxiety agent not cross-tolerant with the benzodiazepines into a chronically anxious group of patients with previous long-term benzodiazepine therapy.

Adult↗
PubMed1987

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

Interactions of the nonbenzodiazepine anxiolytic, buspirone, with serotonin (5-HT) were studied using behavioral and neurochemical procedures. Punished responding was studied in pigeons as this behavior is a generally acknowledged preclinical predictor of anxiolytic activity and because buspirone increases punished responding of pigeons with greater potency and efficacy than in other species. Keypeck responses were maintained under either fixed-interval or fixed-ratio schedules of food presentation; every 30th response produced a brief electric shock and suppressed responding (punishment). Buspirone (0.1-5.6 mg/kg i.m.) produced dose-related increases in punished responding which reached a maximum at 1 mg/kg. A serotonin agonist, MK-212 (0.01 mg/kg), antagonized whereas the 5-HT antagonist, cyproheptadine (0.01 mg/kg), potentiated the effects of buspirone without having behavioral effects of their own. The characteristics of [3H]-5-HT binding in pigeon brain membranes were similar to results reported in mammalian brain. Neither buspirone, MJ-13805 (gepirone, a related analog), nor MJ-13653 (a buspirone metabolite), significantly affected [3H]-5-HT binding and none of the compounds appreciably inhibited uptake of [3H]-5-HT into pigeon cerebral synaptosomes. Hill coefficients significantly less than unity for all drugs except 5-HT suggested multiple serotonergic binding sites for buspirone and analogs. Buspirone and MJ-13805 (1 nM) inhibited [3H]ketanserin binding (a measure of 5-HT2 binding sites) in pigeon cerebrum with Ki values above 10(-6) M. The number of [3H]ketanserin binding sites was estimated to be 109 fmol/mg of protein in pigeon cerebrum compared to 400 fmol/mg of protein in rat cerebrum.(ABSTRACT TRUNCATED AT 250 WORDS)

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

Tissue-dependent alpha adrenoceptor activity of buspirone and related compounds.

The present organ chamber and receptor binding studies were designed to evaluate the alpha adrenoceptor subtype (alpha-1 vs. alpha-2) and tissue selectivity of buspirone and the related compounds, gepirone, isapirone and 1-(2-pyrimidinyl)-piperazine (a metabolite of buspirone). Buspirone, gepirone and isapirone were found to possess weak alpha-1 adrenoceptor affinity (relative to prazosin) but significant and selective alpha-1 adrenoceptor intrinsic efficacy (relative to norepinephrine, phenylephrine and ST-587), which was expressed in a tissue- and species-dependent manner. The rank order for alpha-1 adrenoceptor affinity (isapirone greater than buspirone approximately equal to gepirone) was different from the rank order for alpha-1 adrenoceptor intrinsic efficacy (buspirone greater than gepirone greater than isapirone). The tissues that were the most responsive to norepinephrine and ST-587 (i.e., rat and rabbit aorta) were the same tissues in which the intrinsic efficacy of buspirone was expressed. In contrast, 1-(2-pyrimidinyl)-piperazine was inactive at alpha-1 adrenoceptors. Although no alpha-2 adrenoceptor intrinsic efficacy was observed for any of the compounds, isapirone and 1-(2-pyrimidinyl)-piperazine displayed weak alpha-2 adrenoceptor affinity (relative to rauwolscine). Recent studies have shown buspirone to have an effect on central and peripheral monoaminergic mechanisms. The demonstration in the present study that buspirone and related compounds display significant alpha adrenoceptor activity suggests that alpha adrenoceptor involvement should be considered as a potential contributing factor in the central nervous system and/or peripheral activity of this class of compounds.

Animals↗
PubMed1987

Discriminative stimulus properties of buspirone in the pigeon.

The novel anxiolytic buspirone was administered to pigeons in a two-key drug discrimination task in an effort to characterize the stimulus properties of the drug and thereby aid in isolating the pharmacologic basis for its anticonflict effect. Key pecking was maintained by a schedule of reinforcement in which every 30th injection-appropriate response was reinforced by the presentation of food. Subjects were first trained to discriminate buspirone (1.0 mg/kg) from saline, and then generalization tests were conducted using a cumulative dosing procedure. Cumulative doses of buspirone (1.0-3.0 mg/kg), the buspirone analog MJ 13805 (1.0 mg/kg) and the 5-hydroxytryptamine-1A ligand 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (0.3-1.0 mg/kg) produced in excess of 90% buspirone-appropriate responding, whereas midazolam (0.03-1.0 mg/kg), haloperidol (0.03-1.7 mg/kg), apomorphine (0.03-1.0 mg/kg), clozapine (0.1-3.0 mg/kg), methysergide (0.1-3.0 mg/kg) and the 5-hydroxytryptamine-1B ligand 1-[3-chlorophenyl]piperazine (0.3-10.0 mg/kg) produced little or no buspirone-appropriate responding up to those doses that markedly decreased response rate. These findings support recent behavioral and receptor binding studies suggesting that serotonin receptors, and 5-hydroxytryptamine-1A receptors in particular, may be responsible for mediating the anticonflict effects of buspirone and other atypical anxiolytics. The results also corroborate other behavioral work showing that the anxiolytic effects of buspirone are most likely not mediated by the dopaminergic system.

Animals↗
PubMedDate not supplied

Buspirone, a novel nonbenzodiazepine anxiolytic.

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.

Anti-Anxiety Agents↗
PubMed1998

The effects of buspirone on the behaviour of control and stressed mice.

The effects of buspirone on the locomotor activity and behaviour in the plus-maze and hole-board tests were studied in control and small platform stressed mice. Small platform stress for 24 hours increased the locomotor activity of mice and induced anxiolytic-like effect in the plus-maze and hole-board tests. Administration of buspirone either did not affect (2.0 and 4.0 mg/kg) or inhibited (8.0 mg/kg) locomotions in control animals. The inhibition of locomotor activity by buspirone was greater in small platform stressed mice. In control mice buspirone in doses 2.0 and 4.0 mg/kg exerted anxiolytic effect in the plus-maze and hole board test that was reflected by an increase in the percentage of entries onto and the percentage of time spent on the open arms of the plus-maze and increased number of head-dippings in the hole-board test. In contrast, in small platform stressed mice, buspirone did not induce anxiolytic action in the plus-maze and hole-board tests at any dose tested. In doses 2.0 and 4.0 mg/kg buspirone produced a sedative effect that was reflected by a decrease in the total number of entries made onto the open and into the closed arms of the plus-maze and a decrease in the number of head-dippings and rearings in the hole-board test. These data suggest that small platform stress induces a sensitization of mice to the motor depressant effect of buspirone. At the same time small platform stress induces hyposensitivity to the anxiolytic effect of buspirone. It is proposed that these changes might be due to alterations in the serotonergic transmission or to changes in the release of corticosterone.

Animals↗