Nippon Yakurigaku Zasshi. 1990 Mar;95(3):91-104.
[Electroencephalographic study with buspirone, a novel nonbenzodiazepine anxiolytic, and its major metabolite, 1-(2-pyrimidinyl)piperazine (1-PP), in rabbits]

[Article in Japanese]

Kawasaki H, Nakamura S, Takasaki K.

Department of Pharmacology, Miyazaki Medical College, Japan.

The electroencephalographic (EEG) effects of buspirone and its major metabolite, 1-(2-pyrimidinyl)piperazine (1-PP), were investigated in rabbits with chronic electrode implants, and the effects were compared with those of diazepam. Intravenous administration of buspirone at 0.1 to 1.0 mg/kg evoked an increase in the arousal EEG pattern period (low amplitude fast waves) in the cortical EEG and synchronization of the hippocampal theta waves with decreased voltages, whereas both 1-PP (0.5 to 2.0 mg/kg, i.v.) and diazepam (1.0 and 2.0 mg/kg) evoked an increase in the drowsy EEG pattern periods: high voltage slow waves and spindle bursts in the cortical EEG and desynchronization of the hippocampal theta waves. Buspirone at higher doses caused behavioral excitation in rabbits, whereas both 1-PP and diazepam produced sedation. Buspirone did not affect EEG arousal responses to both auditory stimulation (2,000 Hz, monotone) and electrical stimulation (100 Hz, 0.1 msec, 3-6 V) of the midbrain reticular formation or the posterior hypothalamus. However, 1-PP tended to inhibit the EEG arousal response to auditory stimulation but not brain stimulation, and diazepam markedly suppressed the responses induced by both stimulations. The recruiting response induced by centromedian thalamic stimulation at a low frequency (7 Hz, 0.1 msec, 4-8 V) was not affected by buspirone, 1-PP and diazepam. Neither buspirone nor 1-PP had an effect on the photic driving response to a flash light (2 Hz) in the occipital cortex of the rabbit, whereas the response was suppressed by diazepam. Both buspirone and 1-PP enhanced the duration of after discharges induced by electrical stimulation (50 Hz, 0.5 msec, 4




Boll Soc Ital Biol Sper. 1989 Oct;65(10):945-9.
Effect of buspirone on glutathione hepatic levels in rat.

Micheli L, Fiaschi AI, Runci FM, Giorgi G.

The effect of oral administration of buspirone (0.5-1.0 and 2.0 mg/Kg) on GSH levels was studied in rat liver. The modulating activity of buspirone on hepatic content of this tripeptide is clearly opposite to that of DAZ, put into evidence by us in previous works. Thus our observations let us hypothesize a different mechanism of action for buspirone than that for benzodiazepines.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2624712&dopt=Abstract buspirone Buspar




J Clin Pharmacol. 1989 Jan;29(1):72-8.
Pharmacokinetics of buspirone in elderly subjects.

Gammans RE, Westrick ML, Shea JP, Mayol RF, LaBudde JA.

Department of Metabolism and Pharmacokinetics, Bristol-Myers Pharmaceutical Research, Wallingford, CT 06492-7660.

Twenty-four men and 24 women ages 20-77 years received a single 15 mg oral dose of buspirone followed by 4 days of 15 mg tid administration. Plasma concentrations of buspirone and 1-pyrimidinylpiperazine following both single and multiple dosing were determined by RIA and GCMS, respectively. There were no significant differences between the young and elderly of either gender with regard to buspirone AUC, Cmax, Tmax and half-life values. The 1-PP AUC values were higher for young of either gender compared to the corresponding group of elderly subjects and the 1-PP Cmax values were higher for women than men. These differences are unlikely to be of clinical significance. The buspirone and 1-PP AUC values for a dosing interval during multiple dosing are not significantly different than the respective single dose AUC values. Buspirone treatment was well-tolerated by all subjects even though the 45 mg/day dose was 3 times the recommended starting dose in clinical practice. Overall, the lack of marked or consistent differences in buspirone or 1-PP pharmacokinetics in elderly subjects compared to younger subjects of the same gender suggest there is no need to alter the initial dose of buspirone based solely on patient age.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2708551&dopt=Abstract buspirone Buspar




J Clin Psychopharmacol. 1989 Apr;9(2):132-6.
Buspirone: effects on prolactin and growth hormone as a function of drug level in generalized anxiety.

Tollefson GD, Godes M, Montague-Clouse J, Lancaster SP, Garvey MJ.

Department of Psychiatry, Ramsey Clinic, St. Paul-Ramsey Medical Center, MN 55101.

Certain evidence suggests that buspirone, a novel nonbenzodiazepine anxiolytic, may be a 5-HT1A serotonergic agonist and may antagonize postsynaptic dopaminergic receptors. The latter property raises questions regarding a dyskinesia- or extrapyramidal symptom-inducing potential. We monitored serum prolactin and growth hormone in 10 subjects with generalized anxiety disorder and 10 matched controls before and after 4 weeks of pharmacotherapy. A drug effect upon serotonin-modulated prolactin release or on the tubero-infundibular dopamine axis (prolactin; growth hormone) was negligible at clinically effective dosages of buspirone. Concomitant buspirone levels also failed to demonstrate any significant relationships.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2723131&dopt=Abstract buspirone Buspar




Prog Neuropsychopharmacol Biol Psychiatry. 1989;13(1-2):137-44.
Phase I study of a new antianxiety drug, buspirone.

Murasaki M, Miura S, Ishigooka J, Ishii Y, Takahashi A, Fukuyama Y.

Department of Psychiatry, Kitasato University, School of Medicine, Sagamihara, Japan.

1. A phase I study of buspirone was conducted in 7 healthy male volunteers. 2. Diazepam was selected as the control drug and administered in equipotent doses to buspirone. Dosage was initiated at 2.5mg and doubled until a maximum dosage of 20mg was attained. Subsequently, 10mg was administered once a day for three consecutive days. 3. Clinico-pharmacologically both drugs produced sleepiness/drowsiness, but dizziness, light-headed feeling and feeling of drunkenness were marked only in the diazepam group. 4. No drug-related abnormalities were observed in clinical laboratory test values, endocrinological tests and ECG. 5. On the Uchida-Kraepelin test, no change with the control values was observed under buspirone but subjects administered diazepam exhibited marked deterioration during the latter half of the test. Moreover, in the tapping test, significant impairment was observed in the diazepam group whereas buspirone had no effect. 6. On the EEG some fast waves were observed with diazepam whereas buspirone exhibited slow waves.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2748857&dopt=Abstract buspirone Buspar




Life Sci. 1985 Mar 25;36(12):1149-55.
The non-benzodiazepine anxiolytic buspirone inhibits stress-induced renin secretion and lowers heart rate.

Van de Kar LD, Urban JH, Lorens SA, Richardson KD.

The non benzodiazepine drug, buspirone, produces a dose-dependent biphasic effect on plasma renin activity in non-stressed rats. Low doses (0.1 - 2.0 mg/kg i.p.) decrease while high doses (10.0 - 50.0 mg/kg i.p.) increase plasma renin activity. The maximal decrease in plasma renin activity produced by buspirone (1.0 mg/kg i.p.) was observed 30 minutes post-injection. In addition, buspirone (0.5 and 2.0 mg/kg i.p.) blocked the stress-induced rise in plasma renin activity. This effect of buspirone is in contrast to the previously observed failure of the benzodiazepine anxiolytics to alter the effect of stress on plasma renin activity. Administration of buspirone (0.5 mg/kg i.p.) produced a sustained reduction (15%) in heart rate but did not affect mean arterial pressure. The present data support the view that the mechanism of the anxiolytic action of buspirone is different from that of the benzodiazepines.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2858796&dopt=Abstract buspirone Buspar




Biol Psychiatry. 1985 Sep;20(9):971-9.
Selective interaction of novel anxiolytics with 5-hydroxytryptamine1A receptors.

Peroutka SJ.

Radioligand binding studies were used to analyze the interactions of two novel anxiolytics, buspirone and TVX Q 7821, with a series of 10 neuronal membrane receptor sites. Buspirone (IC50 = 24 nM) and TVX Q 7821 (IC50 = 9.5 nM) display the highest affinity for 5-hydroxytryptamine1A (5-HT1A) binding sites labeled by 3H-8-hydroxy-2-(di-n-pro-pylamino) tetralin (DPAT). By contrast, buspirone is 16-fold weaker at dopamine (D2) receptors (IC50 = 380 nM), whereas TVX Q 7821 is 6-fold less potent at alpha-adrenergic1 sites (IC50 = 58 nM). At the other receptors studied, buspirone and TVX Q 7821 had similar pharmacological profiles. Both agents display moderate affinity for histamine (H1), alpha-adrenergic2, and 5-HT2 binding sites. The drugs are essentially inactive at 5-HT1B, calcium channel antagonist, muscarinic cholinergic, and benzodiazepine receptors. These results suggest that the anxiolytic effects of buspirone and TVX Q 7821 may be mediated by central 5-HT1A receptors.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2862927&dopt=Abstract buspirone Buspar




Methods Find Exp Clin Pharmacol. 1985 May;7(5):231-8.
The effects of buspirone, BMY-13805 and 1-(2-pyrimidinyl)-piperazine on cat spinal reflexes.

Matheson GK, Eison MS.

Buspirone and its analog BMY-13805, clinically effective anxiolytics and their metabolite, 1-PP, were tested on cat spinal reflexes. In the spinal preparation, the monosynaptic reflex and the dorsal root potential were not changed by buspirone, BMY-13805 or 1-PP. Significant changes in the dorsal root potential and monosynaptic reflex were seen after buspirone administration in the intact neuraxis preparation. Generally, these changes had a bimodal pattern, a significant change within 1 hr after buspirone administration, then a period of remittance, followed by a second significant change 3 or more hr later. They included increases in the dorsal root potential and the following changes in the conditioned monosynaptic reflex: an increase in excitatory postsynaptic potential, an increase in postsynaptic inhibition, and decreases in presynaptic inhibition. These data indicate that buspirone does not affect these reflexes directly, but alters supraspinal mechanisms that regulate spinal reflexes.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2863439&dopt=Abstract buspirone Buspar