Eur J Pharmacol. 1987 Jan 28;134(1):113-6.
Pharmacological evidence for the involvement of 1-(2-pyridinyl)-piperazine (1-PmP) in the interaction of buspirone or gepirone with noradrenergic systems.

Giral P, Soubrie P, Puech AJ.

We investigated in mice the effects of one of the principal metabolites of buspirone and gepirone, 1-(2-pyridinyl)-piperazine (1-PmP), on hypothermia and reduced locomotion induced by clonidine (0.25 and 0.06 mg/kg, respectively), tests related to brain alpha-adrenergic function. Both effects were antagonized dose dependently by 1-PmP (1-16 mg/kg i.p.). Moreover, pretreatment with proadifen (50 mg/kg) prevented the reversal by buspirone and gepirone of clonidine-induced hypothermia. This suggests that 1-PmP could be responsible for some of the apparent noradrenergic effects of buspirone and gepirone.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2881793&dopt=Abstract buspirone Buspar




Neuropharmacology. 1987 Feb-Mar;26(2-3):139-46.
Modulation of neuronal activity in the hippocampus by 5-hydroxytryptamine and 5-hydroxytryptamine1A selective drugs.

Peroutka SJ, Mauk MD, Kocsis JD.

The interactions between 5-hydroxytryptamine (5-HT), 8-hydroxy-2-(N,N-dipropylamino)-tetralin (8-OH-DPAT), buspirone, 2-(4-(4-(2-pyrimidinyl)-1-piperazinyl)butyl)-1,2-benzisothiazol-3- (2H)one-1, 1-dioxide-hydrochloride (TVX Q 7821) and ketanserin, and putative 5-HT receptors were analyzed using both radioligand techniques and an in vitro hippocampal slice preparation. The potencies of the drugs were determined at 5-HT1A binding sites labelled by [3H]8-OH-DPAT in hippocampal membranes from the rat. The binding site had similar affinity for 5-HT, 8-OH-DPAT, buspirone and TVX Q 7821, whereas ketanserin was essentially inactive. Physiological effects of these drugs were also examined using an in vitro hippocampal slice preparation. With the exception of ketanserin, application of each drug to the bath modulated the amplitude of the field potential recorded in the pyramidal layer of CA1 evoked by stimulation of Schaffer collaterals. Application of micromolar concentrations of 5-HT produced an initial increase in the population spike followed by a return to near baseline levels within 5 min. By contrast, the amplitude of the population spike was reduced in a dose-dependent manner by micromolar concentrations of 8-OH-DPAT, buspirone and TVX Q 7821, beginning 5 min after application of drug. Ketanserin did not affect the amplitude of the population spike and it did not antagonize the effects of 5-HT, buspirone or TVX Q 7821. Neither buspirone nor 8-OH-DPAT altered the initial increase in population spike induced by 5-HT.(ABSTRACT TRUNCATED AT 250 WORDS)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2884586&dopt=Abstract buspirone Buspar




Biull Eksp Biol Med. 1987 May;103(5):590-2.
[Analysis of the influence of anxiolytics on the pain reactions of rats compared to the effect of morphine]

[Article in Russian]

Korneev AIa, Vasilenko GF, Bragin EO.

Anxiolytic agents, buspirone and diazepam, increase the paw lick latency of rats in hot plate test, the effect being dose-dependent and exceeding that of morphine. The action of buspirone was not accompanied by ataxic and sedative effects which were observed in rats on diazepam. Buspirone (up to 25 mg/kg) and diazepam (up to 5 mg/kg) neither change the tail flick latency nor potentiate the action of morphine in this test. The effect of buspirone on the paw lick reaction in rats may be related to the inhibition of emotional-motivation component of pain reaction.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2885045&dopt=Abstract buspirone Buspar




Naunyn Schmiedebergs Arch Pharmacol. 1987 Jul;336(1):5-10.
Novel anxiolytics discriminate between postsynaptic serotonin receptors mediating different physiological responses on single neurons of the rat hippocampus.

Andrade R, Nicoll RA.

The effects of buspirone on hippocampal pyramidal cells of the CA1 region were examined by means of intracellular recordings in in vitro hippocampal brain slices. Bath administration of buspirone elicited a long lasting hyperpolarization which was mediated by an increase in potassium conductance and resembled the hyperpolarizing component of the response to 5-HT (5-hydroxytryptamine). Buspirone, however, failed to mimic the depolarizing action of 5-HT or to reduce the calcium-activated after hyperpolarization. Quantitative comparisons of the hyperpolarizing responses of 5-HT and buspirone revealed that the maximal hyperpolarization induced by buspirone was significantly smaller than that induced by 5-HT. Since the buspirone induced hyperpolarization was also accompanied by a surmountable antagonism of 5-HT responses, these results indicate that buspirone behaves as a partial agonist at a subpopulation of 5-HT receptors in the CA1 region of the hippocampus. Administration of the buspirone congeners gepirone and isapirone also elicited a hyperpolarization and reduced 5-HT responses, although they lack antidopaminergic activity, indicating that the effects observed with buspirone are unlikely to be mediated through dopamine receptors. These results indicated that novel anxiolytics can discriminate between functional 5-HT receptors. In conjunction with previous biochemical and electrophysiological studies, the present results suggest that their administration might alter the balance of serotonergic actions on postsynaptic neurons.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2888027&dopt=Abstract buspirone Buspar




Pharmacotherapy. 1987;7(3):72-9.
Lack of interaction between cimetidine and buspirone.

Gammans RE, Pfeffer M, Westrick ML, Faulkner HC, Rehm KD, Goodson PJ.

Simultaneous administration of cimetidine and many benzodiazepine anxiolytics has resulted in decreased body clearance and marked prolongation of the half-life of these agents. The pharmacokinetic interaction of buspirone, a new nonbenzodiazepine anxiolytic, and cimetidine was studied in 10 healthy male volunteers. Each received, in order, buspirone 45 mg/day (days 1-7), no drug (days 8-14), cimetidine 1 g/day (days 15-21), buspirone 45 mg/day plus cimetidine 1 g/day (days 22-28), and cimetidine 1 g/day (days 29-31). Buspirone and 1-pyrimidinyl piperazine (1-PP), an active metabolite, pharmacokinetics, urinary excretion of cimetidine, a manual dexterity test, the Stroop color-word interference test, and a visual analog mood scale were evaluated on each treatment. There were no significant (p greater than 0.05) differences among treatments for any measurement except for a slight (31%) but significant (p less than 0.05) increase in the 1-PP Cmax value. These results suggest that within the normal therapeutic dosage ranges for both drugs, it is unlikely that a clinically significant interaction between them will occur.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2888096&dopt=Abstract buspirone Buspar




J Pharmacol Exp Ther. 1987 Dec;243(3):970-7.
Behavioral studies with anxiolytic drugs. IV. Serotonergic involvement in the effects of buspirone on punished behavior of pigeons.

Witkin JM, Mansbach RS, Barrett JE, Bolger GT, Skolnick P, Weissman B.

Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, Maryland.

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 compa




Biull Eksp Biol Med. 1988 Jan;105(1):41-3.
[Interaction of the anxiolytic agent buspirone with serotonin and other synaptic receptors in the human brain]

[Article in Russian]

Korneev AIa, Faktor MI, Chan TB.

Buspirone and Mj 138-05 (up to 0.1 mM) did not displace specifically bound (3H) tryptamine, (3H) strychnine, (3H) flunitrazepam and (3H) imipramine in human cortical and hippocampal membrane preparations. At the same time both compounds displayed similar to serotonin affinity (IC50 in the range of 2-6 microM) for (125I)-LSD specific binding sites in the human cortex and hippocamp. IC50 of serotonin and buspirone and Mj 138-05 for (3H) LSD (2 nM) specific binding sites in the hippocamp was determined as 0.14 microM, 2.3 microM and 6.1 microM, respectively; and for (3H) serotonin specific binding sites in the hippocamp as 0.005 microM, 3.8 microM and 21 microM, respectively. The affinity for human cortex (3H) LSD binding sites was 10-fold lower in case of serotonin and 4-fold lower in case of buspirone and Mj 138-05 than in the hippocamp. However, the affinity for (3H) serotonin binding sites in the cortex was the same as in the hippocamp in case of serotonin and 12-15-fold lower than in the hippocamp in case of buspirone and Mj 138-05. It is concluded that in human brain buspirone and Mj 138-05 interact with micromolar affinity with 5 HT2 and are capable of binding to a subpopulation of 5 HT1 receptors in the hippocamp.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2892547&dopt=Abstract buspirone Buspar




Psychopharmacology (Berl). 1987;93(3):349-52.
Effects of the novel anxiolytics gepirone, buspirone and ipsapirone on free feeding and on feeding induced by 8-OH-DPAT.

Gilbert F, Dourish CT.

Merck Sharp & Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, UK.

The effects of the novel anxiolytics gepirone, buspirone and ipsapirone on free feeding and on feeding induced by the 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), were examined. Gepirone dose-dependently increased feeding 2 and 4 h after injection, the magnitude of the response being larger than previously observed with any other 5-HT1A receptor ligand. Previous studies have suggested that buspirone and ipsapirone can block some of the behavioural effects of 8-OH-DPAT. However, gepirone, buspirone and ipsapirone did not inhibit feeding induced by 8-OH-DPAT. These results indicate that gepirone is a very efficacious appetite stimulant in rats and suggest that gepirone, buspirone and ipsapirone act as 5-HT autoreceptor agonists in the feeding model.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2893412&dopt=Abstract buspirone Buspar