Br J Pharmacol. 1990 Mar;99(3):519-25.
The involvement of 5-hydroxytryptaminergic and dopaminergic mechanisms in the eating induced by buspirone, gepirone and ipsapirone.

Fletcher PJ, Davies M.

Neuropsychiatric Research Unit, University of Saskatchewan, Saskatoon, Canada.

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 raphe 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 inh




Xenobiotica. 1990 Aug;20(8):779-86.
In vitro metabolism of the antianxiety drug buspirone as a predictor of its metabolism in vivo.

Jajoo HK, Blair IA, Klunk LJ, Mayol RF.

Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232.

1. Metabolism of the antianxiety drug buspirone was studied by in vitro incubations with rat liver microsomes and hepatocytes. Metabolites were isolated and purified by h.p.l.c. The purified metabolites were identified by co-elution on h.p.l.c. with authentic standards and by g.l.c.-electron impact mass spectrometry of their trimethylsilyl (TMS) derivatives. 2. Five metabolites of buspirone were identified in the microsomal incubates and seven in the hepatocyte incubates. The major metabolites arose from aromatic hydroxylation at C-5, N-dealkylation of the butyl chain, and hydroxylation at C-6' and C-3' on the azaspirodecanedione moiety. 3. Metabolism of buspirone by rat liver microsomes was NADPH-dependent and was completely inhibited by cytochrome P-450 inhibitors SKF-525A and metyrapone. 4. Metabolites of buspirone formed in vitro were good predictors of the primary metabolites formed in vivo. 5. Hepatocytes and phenobarbital-induced rat liver microsomes were better predictors of in vivo metabolism of buspirone than non-induced rat liver microsomes. These in vitro systems should provide excellent models for studying the metabolism of other azaspirodecanedione-containing drugs.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2219961&dopt=Abstract buspirone Buspar




Pharmacol Biochem Behav. 1990 May;36(1):63-8.
Effects of intrathecal and systemic administration of buspirone on genital reflexes and mating behavior in male rats.

Mathes CW, Smith ER, Popa BR, Davidson JM.

Department of Molecular and Cellular Physiology, Stanford University School of Medicine, CA 94305-5070.

Buspirone was studied to determine whether the detailed profile of male sexual behavior observed following treatment with the prototypical 5-HT1A ligand, 8-OH-DPAT, can be generalized to other 5-HT1A agonist drugs. Systemic and intrathecal (IT) routes of administration were compared. Like DPAT, significant reduction in intromission frequency followed IT infusion of buspirone (80-160 micrograms) as did intraperitoneal (IP) injection (1-4 mg/kg). IT doses of 80-160 micrograms and all IP doses significantly reduced ejaculation latency. Intercopulatory interval significantly decreased following IP buspirone but not after IT infusion although there were trends in that direction. All IP doses and 80 micrograms IT significantly shortened the postejaculatory interval. Buspirone inhibited erection and/or ejaculation in the ex copula reflex test. A decrease in percentage of rats displaying erections and ejaculation occurred following either route of administration. Ejaculation was significantly inhibited at the low IT dose of 40 micrograms. We conclude that buspirone affects sexual behavior very much like DPAT or other 5-HT1A drugs, to the extent known. Sexual effects of buspirone were generally similar regardless of route of administration, but the effective doses were clearly lower with IT treatment.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2349270&dopt=Abstract buspirone Buspar




Am Rev Respir Dis. 1990 Jun;141(6):1527-30.
Effects of buspirone on sleep and respiration.

Mendelson WB, Martin JV, Rapoport DM.

State University of New York, Stony Brook 11794-8101.

Drugs used in the treatment of anxiety are frequently sedating and tend to be respiratory depressants. Buspirone, a nonbenzodiazepine anxiolytic agent, has little reported sedative effect. It has been shown to be a respiratory stimulant in an anesthetized, glomectomized cat model. In this study, we examined the effects of two intraperitoneal single doses (10 and 20 mg/kg) of buspirone on sleep and respiration in unanesthetized, intact, freely moving rats. Buspirone increased sleep latency (p less than 0.0001) and decreased total sleep (p less than 0.02) through reductions in both non-REM and REM sleep. Respiratory rate (p less than 0.0003) and ventilation (p less than 0.004) were significantly increased for 4 h after drug injection. The effects on respiration were independent of those on sleep; stimulation was evident in both waking and non-REM sleep. This study suggests that buspirone, in addition to being free of sedating and respiratory depressant side effects when prescribed for anxiety in humans, may be a respiratory stimulant whose effects persist in sleep.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2350096&dopt=Abstract buspirone Buspar




Neuropharmacology. 1990 May;29(5):463-8.
Selective serotonin1A/1B agonists differentially affect spinal nociceptive reflexes.

Murphy RM, Zemlan FP.

Department of Psychiatry, University of Cincinnati College of Medicine, Ohio 45267-0559.

The purpose of the present experiments was to determine whether serotonin-1A (5-HT1A) and serotonin-1B (5-HT1B) binding sites, recently characterized in the spinal cord of the rat, mediate differential effects of 5-HT on spinal nociceptive processing. Several days after spinal transection at T10, rats were injected intraperitoneally at 20 min intervals, with increasing doses (0, 0.1, 0.4, 2.0, 9.0 mg/kg) of either a 5-HT1A selective agonist (8-OH-DPAT, buspirone) or a 5-HT1B agonist (mCPP, TFMPP). Nociceptive sensitivity was determined by quantifying, in cm2, changes from baseline in the receptive field areas of three spinal nociceptive withdrawal reflexes after noxious (greater than 400 mmHg) levels of mechanical stimulation. The 5-HT1A agonist 8-OH-DPAT and buspirone, significantly increased in a dose-dependent manner the receptive field areas of the three reflexes, with the following log ED50 values (nmol/kg): ventroflexion reflex--buspirone (2.75), 8-OH-DPAT (2.70); dorsiflexion reflex--buspirone (2.91), 8-OH-DPAT (2.67); lateral flexion reflex--buspirone (3.51), 8-OH-DPAT (2.77). The hypersensitivity of the reflexes after pretreatment with buspirone was effectively blocked by the 5-HT1A selective antagonist spiperone, at all doses (0.001, 0.01, 0.1 and 1.0 mg/kg) tested. The 5-HT1B selective agonists mCPP and TFMPP significantly decreased the receptive field are of the ventroflexion reflex (log ED50 values: mCPP, 3.79 nmol/kg; TFMPP, 3.61 nmol/kg) with no significant effect on the dorsiflexion or lateral flexion reflexes.(ABSTRACT TRUNCATED AT 250 WORDS)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2356002&dopt=Abstract buspirone Buspar




Scand J Gastroenterol. 1990 May;25(5):541-4.
Serotonin supersensitivity: the pathophysiologic basis of non-ulcer dyspepsia? A preliminary report of buspirone/prolactin responses.

Dinan TG, Yatham LN, Barry S, Chua A, Keeling PW.

Dept of Psychiatry, Trinity College Medical School, St James's Hospital, Dublin, Republic of Ireland.

Buspirone stimulates central 5-hydroxytryptamine (5HT) receptors and brings about the release of prolactin, and there is evidence to suggest that the extent of prolactin release after a challenge with buspirone is an indicator of the sensitivity of central 5HT receptors. Seventeen patients with a diagnosis of non-ulcer dyspepsia, eight normal healthy volunteers, and six patients with peptic ulcer disease were each given a challenge test of 60 mg buspirone orally, and prolactin release over a 3-h period was monitored. The mean prolactin response was significantly greater in patients with non-ulcer dyspepsia than in healthy controls and peptic ulcer disease patients. The results suggest that central 5HT receptors may be supersensitive in non-ulcer dyspepsia.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2359983&dopt=Abstract buspirone Buspar




J Clin Psychopharmacol. 1990 Jun;10(3 Suppl):111S-115S.
Buspirone in drug users with AIDS or AIDS-related complex.

Batki SL.

Department of Psychiatry, University of California, San Francisco School of Medicine.

Anxiety is a prominent feature of human immunodeficiency virus (HIV)-related psychiatric disorders. Psychiatric disorders are associated with poor drug abuse treatment outcome in both healthy and HIV-infected drug users. While it is important to treat anxiety, the use of traditional antianxiety agents such as benzodiazepines can lead to adverse effects such as sedation and misuse, especially in patients with drug abuse problems. A retrospective chart review was employed to examine the use of buspirone in treating anxiety in intravenous drug users with acquired immune deficiency syndrome (AIDS) or AIDS-related complex who were receiving methadone maintenance treatment. All patients were opiate users, and most were also secondary users of other substances, including stimulants and alcohol. Of 17 patients who were started on buspirone, 14 remained on medication for more than 2 weeks. Of this latter group, all showed at least temporary improvement in one or more of the following areas: subjective reduction of anxiety, reduction of prescribed benzodiazepine use, or reduction in the number of urine tests positive for drugs of abuse, particularly morphine. Buspirone was well tolerated by all but three of these patients; there was no evidence of buspirone misuse. Given its favorable adverse effects profile, buspirone may be particularly useful in the treatment of anxiety in HIV-infected drug users.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2376626&dopt=Abstract buspirone Buspar




J Toxicol Sci. 1990 Apr;15 Suppl 1:15-30.
[Antigenicity study of buspirone hydrochloride in guinea pigs and mice]

[Article in Japanese]

Kawano S, Kohmura H, Ohta S, Takahashi N.

Drug Safety Research Department, Bristol-Myers Research Institute, Ltd., Aichi, Japan.

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.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2376868&dopt=Abstract buspirone Buspar