pharm.gu.se

Recent open clinical studies suggest that pindolol and buspirone may enhance the efficacy and/or shorten the latency to antidepressant action of selective serotonin reuptake inhibitors (SSRI) in unipolar major depressive disorder. The present investigation addressed the possibility that these agents share the ability to enhance the extracellular 5-hydroxytryptamine (5-HT)-elevating response to the SSRI citalopram. For the purpose, in vivo microdialysis in the rat ventral hippocampus was employed. (-)-Pindolol (8 mg/kg s.c.) augmented the citalopram (5 mg/kg s.c.)-induced rise of extracellular 5-HT levels, whereas buspirone (5 mg/kg s.c.) failed to do so. This effect of (-)-pindolol probably reflects its ability to block 5-HT1A autoreceptors, thereby abating the citalopram-induced indirect activation of these sites (secondary to the inhibition of 5-HT reuptake and elevation of extracellular 5-HT in the midbrain raphe). The lack of effect of buspirone in this model indicates that the clinically observed antidepressant augmentation action of buspirone is not mediated indirectly, via enhanced extracellular levels of 5-HT.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8813565&dopt=Abstract buspirone Buspar




Pharmacol Biochem Behav. 1995 Mar;50(3):477-9.
Anticonflict effects of acute and chronic treatments with buspirone and gepirone in rats.

Yamashita S, Oishi R, Gomita Y.

Department of Hospital Pharmacy, Okayama University Medical School, Japan.

The anticonflict activities of buspirone and gepirone were examined in the Vogel's water licking test in rats. Acute treatment with buspirone induced a significant increase in water licking response, but gepirone showed slightly more marked effect than buspirone. The anticonflict activities of these compounds were potentiated by chronic administration. Especially, gepirone exhibited a dramatically remarkable anticonflict effect. These results suggest that gepirone has a great possibility of promising drug for anxiety.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7617689&dopt=Abstract buspirone Buspar




J Affect Disord. 1996 Jul 8;39(2):115-21.
Buspirone augmentation of selective serotonin reuptake inhibitors (SSRIs) in social phobia.

Van Ameringen M, Mancini C, Wilson C.

Department of Psychiatry, McMaster University, Hamilton, Ontario, Canada.

We evaluated the efficacy of buspirone, in the augmentation of social phobic symptom response to the selective serotonin reuptake inhibitors (SSRIs). Ten patients meeting DSM-III-R criteria for generalized social phobia were studied. Patients obtaining only a partial response to an adequate trial of an SSRI, received buspirone in addition to the SSRI for 8 weeks in an open trial. Seven patients (70%) were considered responders (moderate or marked improvement) and 3 (30%) were considered nonresponders (minimal improvement or no change). This study provides clinical evidence suggesting that buspirone augmentation may be a useful clinical strategy in social phobic patients who show a partial response to an SSRI.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8827420&dopt=Abstract buspirone Buspar




Biol Pharm Bull. 1995 Sep;18(9):1296-8.
The effects of the serotonin1A receptor agonist buspirone on tolbutamide-induced hypoglycemia in rats.

Sugimoto Y, Yamada J, Kimura I, Horisaka K.

Department of Pharmacology, Kobe Pharmaceutical University, Japan.

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.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8845828&dopt=Abstract buspirone Buspar




Methods Find Exp Clin Pharmacol. 1996 Sep;18(7):475-80.
Effects of buspirone on operant and nonoperant food intake in food deprived rats.

Ebenezer IS.

Neuropharmacology Research Group, School of Pharmacy and Biomedical Sciences, University of Portsmouth, UK.

The effects of the clinically available 5-HT1A agonist, buspirone, were investigated on food intake in food-deprived rats in both nonoperant and operant feeding paradigms. Buspirone (0.5-2.0 mg/kg), administered subcutaneously (s.c.) 15 min prior to presentation of food, produced a dose-related inhibition of food intake in the nonoperant feeding paradigm. The main inhibitory effects of buspirone were apparent during the first 30 min after food presentation. Likewise, in the operant feeding paradigm, buspirone (0.25-1.0 mg/kg, s.c.) produced a dose-related suppression of food intake in the first 30 min after administration. None of the doses of buspirone produced stereotyped or abnormal behavioral changes in the animals. The results of the study, therefore, suggest that the inhibitory effects of buspirone on food intake in food-deprived rats are unlikely to be due to nonspecific disruptions of behavior. Furthermore, the present findings may have important clinical implications with regard to possible ingestible side effects that use of this drug may have in the treatment of psychiatric disorders.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8900221&dopt=Abstract buspirone Buspar




AIDS. 1996 Oct;10(12):1339-47.
Buspirone, a serotonin receptor agonist, increases CD4 T-cell counts and modulates the immune system in HIV-seropositive subjects.

Hofmann B, Afzelius P, Iversen J, Kronborg G, Aabech P, Benfield T, Dybkjaer E, Nielsen JO.

Department of Clinical Immunology, Copenhagen University Hospitals, Hvidovre, Denmark.

OBJECTIVE: We have previously shown that drugs that decrease intracellular cAMP levels increase/restore the proliferative and cytotoxic capacity of T cells from HIV-seropositive subjects in vitro. Buspirone, a serotonin receptor agonist, indirectly decreases intracellular cAMP levels in T cells and has the same increasing/restoring effect on T-cell proliferation in lymphocytes from HIV-seropositive subjects in vitro. DESIGN: Buspirone was given as a single high dose to six HIV-seropositive subjects, or as continuous medication with increasing dosage over 6 weeks to nine HIV-seropositive subjects, with CD4 T-cell counts of 150-300 x 10(6)/l. RESULTS: Significant increases in CD4 T cells, CD4 percentage and CD4/CD8 ratio were found 1 week after a single high dose of buspirone was administered. With continuous administration, a significant increase in CD4 T cells was observed after 1 and 4 weeks. Serum HIV RNA showed a significant decrease 1 h after a single dose of buspirone was administered. With continuous administration of buspirone, plasma HIV RNA first increased within the first 2 weeks of treatment and then decreased towards and below baseline concurrently with a significant decrease in CD8T cells. The proliferative T-cell response to poke weed mitogen and membrane expression of IL-2R increased significantly during continuous treatment with a significant decrease in expression of HLA-DR on CD8+ T cells. Development of "flu-like' symptoms, so severe that two patients withdrew from the study and two patients ceased medication before time, was a clinical indication of modulation of the immune system by buspirone. CONCLUSION: The study shows




Eur J Pharmacol. 1996 Oct 10;313(1-2):25-34.
Role of 5-HT1A receptors in the ability of mixed 5-HT1A receptor agonist/dopamine D2 receptor antagonists to inhibit methylphenidate-induced behaviors in rats.

Kleven M, Prinssen EP, Koek W.

Centre de Recherche Pierre Fabre, Castres, France.

Behavioral effects produced by the indirect-acting dopamine receptor agonist, methylphenidate (40 mg/kg i.p.) were examined in rats after administration of the 5-HT1A receptor agonists (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and flesinoxan, the mixed 5-HT1A receptor agonist/dopamine D2 receptor antagonists buspirone and 1-[-4-fluorobenzoylamino)ethyl]-ethyl]-4-(7-methoxynaphthyl) piperazine (S 14506), the neuroleptics haloperidol and clozapine, and the sigma receptor ligand/partial 5-HT1A receptor agonist alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine-butanol (BMY 14802). All of the compounds produced dose-related decreases in methylphenidate-induced stereotyped gnawing, and, as gnawing was inhibited, other methylphenidate-induced responses (i.e. sniffing, rearing and locomotion) appeared. Higher doses of haloperidol and buspirone, but none of the remaining compounds, inhibited these other responses, so that the behavior of the methyphenidate-treated animals became similar to that of normal controls. Pretreatment with the 5-HT1A receptor antagonist N-[2-4-(2-methoxyphenyl)-1-piperazinyl]-ethyl]-N-(2-pyridinyl)- cyclohexanecarboxamide (WAY-100635; 0.63 mg/kg s.c.) blocked the ability of 8-OH-DPAT, S 14506 and flesinoxan to inhibit methylphenidate-induced gnawing, demonstrating the involvement of 5-HT1A receptors in their ability to inhibit methylphenidate-induced behaviors. In contrast, pretreatment with WAY-100635 did not alter the ability of haloperidol, clozapine, buspirone, or BMY 14802 to inhibit methylphenidate-induced gnawing, or in the case of haloperidol and buspirone, to normalize behavior. The results indicate that mixed compounds with 5-HT1A receptor agonist and dopamine

indyvax.iupui.edu

Chronic buspirone or ipsapirone (3 mg/kg, twice daily) administration to rats for 10 days decreased the sensitivity of inhibition of single-unit activity of serotonergic dorsal raphe neurons to a challenge by each drug. The ED50 for buspirone was increased from 0.1 mg/kg to 1.8 mg/kg, and the ED50 for ipsapirone was increased from 0.7 mg/kg to 1.2 mg/kg. The binding properties (Kd and Bmax) of [3H]8-OH-DPAT to membranes of cerebral cortex and hippocampus were unaffected by chronic administration of either buspirone or ipsapirone. Chronic buspirone or ipsapirone administration increased the tolerance of the hypothalamic-pituitary-adrenal axis (HPAA) following a challenge by each drug. The ED50 for elevation of plasma corticosterone levels was increased from 4.0 mg/kg to 7.6 mg/kg for buspirone and 6.2 mg/kg to 8.0 mg/kg for ipsapirone. Chronic buspirone administration decreased the basal activity of the HPAA by 63%. Chronic buspirone administration did not alter the plasma corticosterone response of the HPAA to a 1-min episode of rotational stress. (Mg2+)-ATPase, (Na+ + K+)-ATPase, (Ca2+ + Mg2+)-ATPase and calmodulin-stimulated (Ca2+ + Mg2+)-ATPase activities of erythrocyte plasma membrane were unaffected by either chronic or acute buspirone treatment, or by the addition of the drug to the in vitro assay systems.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8919656&dopt=Abstract buspirone Buspar