Nippon Yakurigaku Zasshi. 1991 Oct;98(4):259-72.
[Electroencephalographic study with SC-48274, a novel nonbenzodiazepine anxiolytic in conscious rabbits]

[Article in Japanese]

Kawasaki H, Takasaki K.

Department of Pharmacology, Miyazaki Medical College, Japan.

The electroencephalographic (EEG) effects of SC-48274 were investigated in conscious rabbits and compared with those of buspirone and diazepam. SC-48274 (20-30 mg/kg, i.v.) evoked an increase in drowsy EEG pattern period. Diazepam (2-3 mg/kg, i.v.) also increased the drowsy EEG pattern, while buspirone (0.5 mg/kg, i.v.) increased the arousal EEG pattern period. Neither SC-48274 nor buspirone affected the EEG arousal response to both auditory stimulation and electrical stimulation of the midbrain reticular formation of the posterior hypothalamus, while diazepam markedly suppressed the responses to both stimulations. The recruiting response to centromedian thalamic stimulation was not significantly affected by SC-48274 and buspirone, and it was slightly enhanced by diazepam. Neither SC-48274 nor buspirone had any effect on the photic driving response to flash light in the occipital cortex, while the response was markedly suppressed by diazepam. The duration of afterdischarges induced by electrical stimulation of the dorsal hippocampus was slightly inhibited by SC-48274 and markedly inhibited by diazepam, while buspirone enhanced the duration. These results suggest that the EEG effect of SC-48274 is quite different to those of buspirone and diazepam with respect to the qualitative aspects. We also suggest that SC-48274, unlike diazepam, is an effective anxiolytic drug with weak sedation.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1687040&dopt=Abstract buspirone Buspar




Neuroscience. 1992;46(1):83-90.
Pindolol antagonizes the effects on hippocampal rhythmical slow activity of clonidine, baclofen and 8-OH-DPAT, but not chlordiazepoxide and sodium amylobarbitone.

Coop CF, McNaughton N, Scott DJ.

Department of Psychology, University of Otago, Dunedin, New Zealand.

Buspirone, benzodiazepines, barbiturates and ethanol all reliably reduce the frequency of reticular-elicited hippocampal rhythmical slow activity. In the present experiments we tested a number of drugs which are not usually used for treating generalized anxiety disorders but which have been reported to have some anxiolytic properties. Clonidine (0.3 mg/kg, i.p.), baclofen (6 mg/kg, i.p.) and 8-hydroxy-di-n-propylamino tetralin (8-OH-DPAT) (2.5 mg/kg, i.p.) all reduced the frequency of rhythmical slow activity. The effect of all three drugs was reduced by the 5-hydroxytryptamine 1a antagonist pindolol (2 mg/kg, i.p.). Pindolol had no effect on the reduction in rhythmical slow activity produced by sodium amylobarbitone, as has been previously reported for the benzodiazepine chlordiazepoxide. Flumazenil (10 mg/kg, i.p.), a benzodiazepine receptor antagonist, reduced the effects of chlordiazepoxide (5 mg/kg, i.p.), but not buspirone (10 mg/kg, i.p.). A combination of the selective beta 1 adrenergic receptor antagonist metoprolol (20 mg/kg, i.p.) and the beta 2 adrenergic receptor antagonist ICI 118,551 (4 mg/kg, i.p.) did not reduce the effects of either buspirone (10 mg/kg, i.p.) or diazepam (1 mg/kg, i.p.). These data show that there are at least two separate routes through which anxiolytic agents reduce the frequency of hippocampal rhythmical slow activity. Buspirone, clonidine, baclofen and 8-OH-DPAT act via a system dependent on 5-hydroxytryptamine 1a receptor activation. Benzodiazepines act via activation of the benzodiazepine receptor and probably share with barbiturates action at the GABA-benzodiazepine-chloride ionophore complex but do not produce their effects, directly or indirectly,




Eur J Pharmacol. 1991 Nov 5;204(2):141-7.
Buspirone, ipsapirone and 1-(2-pyrimidinyl)-piperazine decrease cold-induced thyrotropin secretion in rats.

Broqua P, Baudrie V, Bluet-Pajot MT, Chaouloff F.

Laboratoire de Pharmacologie, Groupe de Neuropharmacologie, CNRS, Paris, France.

The aim of this study was to analyse the effects of the 5-HT1A receptor-related antidepressants/anxiolytics, buspirone and ipsapirone (1-10 mg/kg i.v.), and those of their common metabolite, the alpha 2-adrenoceptor antagonist, 1-(2-pyrimidinyl)-piperazine (1-PP, 1-10 mg/kg i.v.), on cold-induced thyrotropin (TSH) secretion in conscious catheterised rats. The effects of the centrally acting 5-HT1A receptor agonist, 8-hydroxy-2-(d-n-propylamino)tetralin (8-OH-DPAT, 0.1-1 mg/kg i.v.), and of the peripherally acting 5-HT1A receptor agonist, N,N-dipropyl-5-carboxamidotryptamine (DP-5-CT, 0.1-1 mg/kg i.v.), were also included in this study. Buspirone, ipsapirone, and 1-PP dose dependently decreased cold-induced TSH secretion throughout the 90 min of analysis. However, the preventive effect of 1-PP was reached with a lower dose (3 mg/kg) than that needed for the parent compound (10 mg/kg). 8-OH-DPAT administration diminished but did not prevent cold-induced TSH secretion, while only the highest dose of DP-5-CT diminished secretion (1 mg/kg). Lastly, the TSH-releasing hormone (TRH)-induced TSH secretion was left unaffected by either buspirone or ipsapirone pretreatment (10 mg/kg), but was diminished by 1-PP pretreatment (3 mg/kg). These data suggest that both central 5-HT1A receptors and alpha 2-adrenoceptors mediate the effects of azapirones on cold-induced TSH secretion.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1687218&dopt=Abstract buspirone Buspar




Pharmacol Biochem Behav. 1991 Dec;40(4):733-7.
Comparison of routes of administration and time course effects of zacopride and buspirone in mice using an automated light/dark test.

Young R, Johnson DN.

Department of Pharmacology, A.H. Robins Co., Inc., Richmond, VA 23261-6609.

The behavioral effects of zacopride and buspirone were assessed in mice in a fully automated 2-compartment light/dark test. A significant increase in time mice spent in the lit area was used as an indication of anxiolytic-like action. Doses of zacopride from 0.0001 to 17.8 mg/kg, IP, and buspirone from 3.16 to 17.8 mg/kg, IP, produced significant increases in time mice spent in the lit area of the chamber. In addition, zacopride and buspirone were compared for oral potency and for duration of action after IP and PO administration. Zacopride and buspirone produced anxiolytic-like activity between doses of 0.001 to 100.0 mg/kg, PO, and 10.0 to 56.2 mg/kg, PO, respectively. The duration of effect of buspirone was 2 to 4 h after IP or PO administration, while that for zacopride was greater than or equal to 16 h by either route of administration. Thus, when compared for anxiolytic-like effects in this test, zacopride is a more potent and longer acting agent than buspirone.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1687761&dopt=Abstract buspirone Buspar




Pharmacol Biochem Behav. 1991 Dec;40(4):787-94.
Acute administration of diazepam and buspirone in rats trained on conflict schedules having different degrees of predictability.

Costello NL, Carlson JN, Glick SD.

Department of Pharmacology and Toxicology, Albany Medical College, NY 12208.

The anti-conflict activities of diazepam and buspirone were examined on three schedules designed to condition the suppression of licking. The schedules differed in the degree to which they predicted (signalled) the presentation of a conflict inducing electric shock. The first study investigated the effects of three doses of diazepam (0.5, 2, and 5 mg/kg IP) on a predictable, a moderately predictable, and an unpredictable schedule of shock presentation. Diazepam induced a significant increase from baseline in licking during the shock component on all three schedules. These anticonflict effects were the most consistent on the predictable schedule, and least consistent on the unpredictable schedule. A second experiment investigated the anticonflict activity of three doses of buspirone (0.125, 0.25, and 0.625 mg/kg SC) on each of these three schedules. The predictable and moderately predictable schedules failed to detect anticonflict activity at any dose of buspirone. However, the lowest dose (0.125 mg/kg) of buspirone increased shocked licking and the highest dose (0.625 mg/kg) decreased shock component licking on the unpredictable schedule. Thus the unpredictable schedule was sensitive to both anticonflict (anxiolytic) and proconflict (anxiogenic) effects of buspirone.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1687764&dopt=Abstract buspirone Buspar




Eur J Pharmacol. 1991 Sep 24;202(3):379-83.
Buspirone inhibits corticotropin-releasing factor and stress-induced cecal motor response in rats by acting through 5-HT1A receptors.

Martinez JA, Bueno L.

Department of Pharmacology, INRA, Toulouse, France.

The effect of buspirone on corticotropin-releasing factor (CRF) and stress-stimulated cecal motility and its antagonism by 5-HT1A (spiroxatrine) and sigma (BMY 14802) antagonists were evaluated by electromyography in rats equipped with chronically implanted electrodes on the cecum and a small catheter into the right lateral ventricle of the brain. Exposure to mental stress, consisting of a fear-conditioned response, increased during 30 min the frequency of cecal spike bursts significantly (P less than 0.01). The frequency of cecal spike bursts was also increased following intracerebroventricular injection of CRF (500 ng/kg). Buspirone (1 mg/kg s.c.) abolished the stimulatory effects of mental stress and CRF on cecal motility. Whereas spiroxatrine (0.5 mg/kg s.c.) blocked the effect of buspirone on the colonic hypermotility induced by i.c.v. injection of CRF, BMY 14802 at a similar dose (0.5 mg/kg s.c.) was unable to block the action of buspirone. It is concluded that s.c. administration of buspirone suppresses the stress-induced cecal motor response through 5-HT1A receptors, probably by inhibiting the central or peripheral pathways involved in CRF mediation of these effects.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1748159&dopt=Abstract buspirone Buspar




Psychopharmacology (Berl). 1991;105(4):578-82.
Low but not high doses of buspirone reduce the anxiogenic effects of diazepam withdrawal.

File SE, Andrews N.

Psychopharmacology Research Unit, UMDS Division of Pharmacology, London University, Guy's Hospital, UK.

After 21 days of treatment with diazepam (2 mg/kg/day IP) rats were tested 24 h after the last injection in the social interaction and elevated plus-maze tests of anxiety. Compared with control-treated rats, they showed significant decreases in social interaction, in the % numbers of entries onto open arms of the plus-maze and in the % of time spent on the open arms, indicating an anxiogenic response on withdrawal from diazepam. Buspirone (200 micrograms/kg SC) significantly increased social interaction in diazepam withdrawn rats and in the plus-maze also this dose significantly reversed the anxiogenic effects of diazepam withdrawal. Buspirone (400 micrograms/kg SC) was without effect in the plus-maze, but buspirone (800 micrograms/kg SC) significantly decreased the % of time spent on open arms in control-treated rats, indicating an anxiogenic effect. In the social interaction test buspirone (800 micrograms/kg SC) was without significant effect. The contrasting effects of the 200 and 800 micrograms/kg doses are discussed in terms of the pre- and post-synaptic actions of buspirone. The findings are consistent with earlier proposals that the increased anxiety during benzodiazepine withdrawal is at least partly caused by an increased release of hippocampal 5-HT.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1771225&dopt=Abstract buspirone Buspar




Neuropharmacology. 1991 Aug;30(8):855-63.
Neurochemically dissimilar anxiolytic drugs have common effects on hippocampal rhythmic slow activity.

McNaughton N, Coop CF.

Department of Psychology, University of Otago, Dunedin, New Zealand.

Previous experiments have shown that anxiolytic drugs reduce the frequency of hippocampal rhythmic slow activity, induced by high frequency stimulation of the reticular formation and flatten the function relating threshold septal stimulation to the frequency of driven rhythmic slow activity. All of the drugs involved are known to augment GABAergic transmission. The present experiments investigated the effects of the novel anxiolytic compound buspirone which, unlike conventional anxiolytics, does not interact with GABA, yet is a clinically effective anxiolytic. Buspirone (0.156-40 mg/kg, i.p.) was found to reduce the frequency of reticular-elicited rhythmic slow activity, in a similar manner to chlordiazepoxide (0.019-20 mg/kg, i.p.). Buspirone did not change the linearity of the voltage-frequency function. Buspirone (10 mg/kg, i.p.) also altered the threshold for septal driving of rhythmic slow activity, in a similar manner to classical anxiolytics. The combination of chlordiazepoxide (5 mg/kg, i.p.) with corticosterone (0.2 mg, s.c.) removed the minor differences between buspirone and chlordiazepoxide in both the septal and reticular tests. These results show that buspirone altered the control of rhythmic slow activity in the hippocampus, in a manner which appeared functionally equivalent to other anxiolytics but which depends on mechanisms which are likely to be neurally and pharmacologically distinct from those of other anxiolytic drugs.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1780042&dopt=Abstract buspirone Buspar