Neuropharmacology. 1989 Aug;28(8):799-803.
Comparison of changes in the EEG of freely moving rats induced by enciprazine, buspirone and diazepam.

Nickel B, Szelenyi I.

Department of Pharmacology, ASTA Pharma AG, Frankfurt, Federal Republic of Germany.

The effect of enciprazine, buspirone and diazepam was investigated on the cortical electrical activity in freely-moving rats. Enciprazine (5 mg/kg, i.p.) and buspirone (5 mg/kg, i.p.) induced comparable changes, consisting in decreases of mean power values in delta and theta and increases in alpha and beta EEG frequency bands. Regarding only a particular area of the brain or particular frequency bands, these two compounds could not be clearly separated from each other. Changes in frequency bands induced by O-methoxy-phenyl-piperazine (5 mg/kg i.p.) (D 15157), the presumed main metabolite of enciprazine, were dose-related to that caused by the parent compound. The second metabolite (R,S)-1-4-(1-methoxy-4-hydroxy-phenyl)piperazin-1-yl-3-(3,4,5- trimethoxyphenoxy)propan-2-ol-dihydrochloride (D 20092) (5 mg/kg i.p.) evoked only minimal changes in the different frequency bands of the rats. The power spectra did not significantly differ from those seen in animals treated with saline. The action of diazepam (2 mg/kg i.p.) was characterized by decreases in alpha and delta frequency bands, accompanied by marked increases in fast beta waves. The marked frequency shifts caused by buspirone and enciprazine could clearly be differentiated from the EEG changes evoked by the minor tranquilizer, diazepam.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2571102&dopt=Abstract buspirone Buspar




Pain. 1989 Oct;39(1):109-13.
Antinociceptive effects of the novel anxiolytic buspirone in three pain tests in rats.

Giordano J, Rogers L.

Department of Pharmacology Drake University, College of Pharmacy and Health Sciences, Des Moines, IA 50311.

The analgesic efficacy of the novel anxiolytic buspirone in tests of acute thermal, mechanical and formalin-induced chemical-inflammatory pain were examined. Buspirone produced dose- and time-dependent analgesia in all nociceptive tests, with greatest effects against chemical and mechanical pain. Buspirone was less potent in the thermal pain test. Locomotor and overt behavioral activities were unaffected at any dose tested. These data suggest the potential use of buspirone in the management of specific types of pain.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2573030&dopt=Abstract buspirone Buspar




Neuropharmacology. 1990 Feb;29(2):181-4.
Binding of umespirone to the sigma receptor: evidence for multiple affinity states.

Itzhak Y, Ruhland M, Krahling H.

Department of Biochemistry and Molecular Biology, REPSCEND Labs, University of Miami School of Medicine, Florida 33101.

Umespirone (3,7-diazabicyclo[3.3.1]nonane-2,4,6,8-tetraon; KC9172) has been recently described as a potential antipsychotic/anxiolytic. In the present study the interaction of umespirone and several other typical and atypical psychotropics with the sigma and phencyclidine (PCP) receptor subtypes, in rat brain membranes, was investigated. Umespirone, haloperidol, chlorpromazine and buspirone, but not clozapine and diazepam, compete for the binding of the sigma-ligand, (+)[3H]-3-(3-hydroxy-phenyl)-N-1-(propyl) piperidine [(+)]3H-3-PPP]. The compounds do not compete for the binding of PCP-receptor ligands. Umespirone, buspirone and (+)-3-PPP, unlike haloperidol and chlorpromazine, inhibit (+)[3H]-3-PPP binding in a manner indicating the existence of high and low affinity states of the sigma receptor. 5'-Guanylylimidodiphosphate (Gpp(NH)p; 0.1mM) abolishes the high affinity binding component associated with the binding of umespirone, buspirone and (+)-3-PPP, but does not affect the affinities of haloperidol and chlorpromazine for the sigma receptor. These findings suggest that different coupling states of the sigma receptor may be associated with the binding of umespirone and buspirone compared to the binding of haloperidol and chlorpromazine.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1970425&dopt=Abstract buspirone Buspar




Eur J Pharmacol. 1989 Sep 22;168(3):393-6.
Intra-hippocampal buspirone in animal models of anxiety.

Kostowski W, Plaznik A, Stefanski R.

Department of Pharmacology and Physiology of the Nervous System, Institute of Psychiatry and Neurology, Warsaw, Poland.

The effect of intra-hippocampal injections of the serotonergic 5-HT1A receptor agonist, buspirone, on rat exploratory activity was evaluated in the 'open field' and 'elevated plus maze' tests. The dose of 2.5 micrograms, but not of 1 microgram, of buspirone administered to the dentate gyrus of the hippocampus increased the time spent on exploration of open arms in the elevated plus maze, as well as it increased the number of central entries in the open field. The results indicate an anti-emotional influence of local stimulation of 5-HT1A receptors by buspirone.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2573536&dopt=Abstract buspirone Buspar




Drug Metab Dispos. 1989 Nov-Dec;17(6):634-40.
Metabolism of the antianxiety drug buspirone in human subjects.

Jajoo HK, Mayol RF, LaBudde JA, Blair IA.

Department of Chemistry, Vanderbilt University School of Medicine, Nashville, TN.

The metabolism of an oral dose (20 mg) of the antianxiety drug buspirone labeled with 14C/15N was studied in human subjects. 15N was incorporated in the molecule to facilitate structural characterization of the metabolites by mass spectrometry. Urine samples were collected at intervals up to 24 hr and analyzed for radioactivity. Cumulative urinary excretion accounted for 50% of the dose in 24 hr. The urine was hydrolyzed with beta-glucuronidase/arylsulfatase and the deconjugated metabolites were isolated and purified by HPLC. The purified metabolites were identified by GC/MS, 1H-NMR, and comparison with authentic standards when available. Seven metabolites of buspirone were identified unambiguously, together with unchanged drug. Hydroxylation alpha to the glutarimidyl carbonyl at the 6'-position on the spiro ring system, hydroxylation at the 5-position on the pyrimidine ring, and N-dealkylation of the butyl-substituted side chain were major routes of metabolism. The identified metabolites accounted for 88% of the total radioactivity in the urine. A scheme for metabolism of buspirone in human subjects has been proposed.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2575499&dopt=Abstract buspirone Buspar




Psychopharmacology (Berl). 1989;99(3):427-9.
Anti-conflict efficacy of buspirone following acute versus chronic treatment.

Schefke DM, Fontana DJ, Commissaris RL.

Department of Pharmaceutical Sciences, College of Pharmacy, Wayne State University, Detroit, MI 48202.

In many animal studies, acute treatment with the novel anxiolytic agent buspirone exhibits only minimal "anxiolytic efficacy" (i.e., increases in punished responding) when compared to benzodiazepines and barbiturates. The present studies examined the effects of acute pre-test challenges with buspirone in subjects receiving chronic post-test buspirone or saline treatments. Chronic post-test treatment with buspirone (4 mg/kg/day for 4 weeks, followed by 8 mg/kg/day for 12 weeks) did not significantly affect CSD behavior. Consistent with previous reports, acute pre-test administration of buspirone (0.125-2 mg/kg, IP) to subjects receiving chronic post-test saline treatment resulted in only a modest anti-conflict effect in the CSD paradigm (approximately ten shocks over control). In contrast, subjects chronically treated with buspirone exhibited a dramatically greater anti-conflict effect following acute challenge with buspirone (up to 40 shocks over control). These data are consistent with the hypothesis that the full anxiolytic efficacy of buspirone requires repeated administration.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2594911&dopt=Abstract buspirone Buspar




Neuropsychobiology. 1989;21(3):124-30.
Analysis of individual symptoms in generalized anxiety--a pooled, multistudy, double-blind evaluation of buspirone.

Feighner JP, Cohn JB.

Feighner Research Institute, Encinitas, Calif.

Pooled data for 427 patients with generalized anxiety disorders were analyzed retrospectively from six double-blind trials evaluating buspirone, a nonbenzodiazepine anxiolytic, in the treatment of generalized anxiety disorder. After a 4- to 7-day washout period, patients were allocated at random to receive treatment over a 4-week period. Buspirone dose ranged from 10 to 60 mg. Patients were assessed on entry and at weekly intervals using the 14 symptom groups (items) of the Hamilton Anxiety Rating Scale (HAM-A). Buspirone improved all symptom groups significantly; onset of anxiolytic activity was observed at week 1 in 3 groups of psychic symptoms of anxiety. Within 2 weeks, 8 of the 14 symptom groups were improved significantly by buspirone versus placebo, and symptoms of anxiety improved further up to the 4-week end point. Psychic symptoms of anxiety improved earlier in general than the somatic symptoms of anxiety. At the end of treatment, analyses of the HAM-A scores indicated that all of the 14 symptom groups (individual items), the total HAM-A score, and the 2 composite Psychic and Somatic Anxiety Factors were significantly improved with buspirone as compared to placebo. The beneficial effects of buspirone were not compromised by any significant side effects.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2615929&dopt=Abstract buspirone Buspar




Pharmacol Biochem Behav. 1989 Oct;34(2):349-53.
Effects of buspirone on plasma catecholamines, heart rate, and blood pressure in stressed and nonstressed rats.

Taylor J, Harris N, Krieman M, Vogel WH.

Department of Pharmacology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107.

The influence of buspirone upon plasma catecholamine levels, heart rate, and mean arterial blood pressure was studied in stressed and nonstressed rats. Measures were obtained directly via indwelling aortic catheters. Drug or vehicle were given acutely (10 mg/kg, IP) or twice a day for 10 days (10 mg and 20 mg/kg, SC). In nonstressed rats, a single dose of buspirone increased markedly plasma norepinephrine and epinephrine levels and decreased significantly heart rate with no effect on blood pressure. During stress, stress-induced increases in catecholamine levels were further elevated by the drug, whereas stress-induced increases of heart rate and mean arterial blood pressure were reduced. In chronically-pretreated rats, the effects of buspirone were similar to those observed after an acute injection. These effects of buspirone on plasma catecholamines are very different from those seen with other anxiolytics, whereas effects on heart rate and blood pressure are more similar.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2622992&dopt=Abstract buspirone Buspar