Dose-dependent response of central dopaminergic systems to buspirone in mice.

Buspirone, a partial agonist of 5-hydroxytryptaminelA autoreceptors, preferentially blocks the presynaptic rather than the postsynaptic D2 dopamine (DA) receptors. Behavioural effects of a wide dose range of buspirone were therefore studied in mice. Buspirone at 0.625 to 5 mg/kg ip induced stereotyped cage climbing behaviour which was antagonized by pretreatment with haloperidol, alpha-methyl-p-tyrosine and small doses of apomorphine. Buspirone at 10, 20 and 40 mg/kg ip induced catalepsy and antagonized oral stereotypies induced by high doses of apomorphine and methamphetamine and apomorphine-induced cage climbing behaviour. The findings indicate that buspirone at 0.625 to 5 mg/kg selectively blocks the presynaptic mesolimbic D2 DA autoreceptors and releases DA which stimulates the postsynaptic mesolimbic D2 and D1 DA receptors and induces cage climbing behaviour. Buspirone, at 10, 20 and 40 mg/kg blocks the postsynaptic striatal and mesolimbic D2 and D1 DA receptors. Pretreatment with 1-tryptophan, dexfenfluramine and fluoxetine antagonized buspirone induced cage climbing behaviour and potentiated buspirone induced catalepsy. Pretreatment with trazodone, mianserin and p-chlorophenylalanine potentiated buspirone induced cage climbing behaviour and antagonized buspirone induced catalepsy. The results indicate that drugs which influence the activity of central serotonergic systems modulate the intensity of buspirone induced cage climbing behaviour and catalepsy.

Effect of anxiolytics on blood sugar level in rabbits.

Anxiety disorders are more prevalent not only in normal individuals but also in diabetes mellitus. Diazepam, a benzodiazepine, and buspirone, an azaspirodecanedione, are the most often prescribed anxiolytics. Present study was aimed to investigate the effect of diazepam and buspirone on the blood sugar levels in rabbits. Buspirone (0.5 mg/kg/day p.o.) and diazepam (0.6 mg/kg/day p.o.) did not affect the glucose levels in rabbits even after one month of treatment. Present findings suggest that these two anxiolytics have minimal effect on blood sugar control.

Are 5-HT1A receptors involved in the control of reflex bradycardia induced by intracoronary injection of contrast medium in humans?

Transient vagal bradycardia occuring during coronary arteriography (CA) immediately following intracoronary injection of ionic contrast medium is believed to be a component of the von Bezold-Jarisch reflex (BJ). Data obtained from experimental animals using buspirone (BSP) and other 5-HT1A receptor ligands suggest that these serotonergic receptors modulate the excitability of cardiac vagal motoneurones (CVM). This is a preliminary investigation of the possible effects of BSP in altering the bradycardia of patients submitted to CA for diagnostic purpose. Patients were divided into two age-and racematched groups: control (C:N=45, age 58.6 + 1.6 years, mean arterial blood pressure (MAP) 109 + 2.4 mmHg, heart rate (HR) 79 + 2.9 bpm) and BSP-treated (B:N=14, age 58.9 + 2.1 years, MAP 111 + 4.5 mmHg, HR 76 + 3.4 bpm). The prevalent underlying pathology was coronary artery disease. Patients with acute angina, congestive heart failure, symptomatic arrhythmia and patients requiring atropine were excluded. CA was performed by a standard procedure using diatrizoate (MD-76() as contrast agent. The left and then the right coronary ostia were selectively catheterized and 8 ml of contrast medium was injected (over a period of 3 sec). HR was measured from ECG tracing before and after contrast injection into the left (LC) and right (RC) coronary arteries. Peak bradycardia was measured as the longest R-R interval during the first 15 sec after the injection minus the pre-injection R-R value, and reported as deltaR-R. Group B patients received BSP tablets 48 and 24 h before the examination (30 mg/day po). There was no statistically significant difference (P>0.05) in bradycardia between groups (C:LC=-147 + 23,RC=-155+25; B:LC=-143 + 44,RC=-234 + 56 msec). These results suggest that, in contrast to experimental animals, the central 5-HT1A receptors of humans are not relevant for modulating the excitability of CVM in the BJ reflex. However, since drugs and diseases can affect the responses, further studies are necessary to clarify this issue.

Eficácia e tolerabilidade do cloridrato de buspirona no tratamento dos sintomas psicossomáticos na clínica cardiológica / Efficacy and Tolerability of Buspirone Hydrochloride in the Treatment of Psychosomatic Symptoms in Cardialogy

Objetivo - Avaliar a eficácia e a segurança do cloridato de buspirona em pacientes de clínica cardiológica com manifestaçöes de ansiedade generalizada. Métodos - Cinquenta pacientes ambulatoriais de clínica cardiológica com sintomas psicossomáticos cardiovasculares foram tratados com cloridato de buspirona na dose inicial de 5mg 3 vezes ao dia, por 6 semanas. Resultado - Os resultados obtidos foram considerados bons em 76//, regulares em 18// e ineficazes em 6// dos casos. Treze pacientes (26//) relatarm pelo menos uma reaçäo adversa, os efeitos colaterais relatados foram sonolência, cefaléia, flatulência, zumbido, congestäo nasal e boca seca. Näo houve necessidade de interrupçäo do tratamento. Conclusäao - O cloridato de buspirona é uma alternativa válida no tratamento da ansiedade patológica em pacientes onde o estado de vigilância e habilidade psicomotora devem ser preservados

Purpose - To evaluate the efficacy of buspirone hydrochloride in patients of the cardiologic clinic with generalized anxiety. Méthods - Fifty out-patients with psychossomatic cardiovascular symptons in cardialogy were treated for six weeks with initial dose of 5mg of baspirone hydrochloride t.i.d. Results - The results obtained were good in 76% of the patients, foir in 18% and ineffective in 6% of the cases. Thirteen patients (26%) reported at least one adverse event, the side effects reported were: somnolence, headache, flatulence, tinnitus, nasal congestion and dry mouth. No interruption of the treatment was needed. Conclusion - Buspirone hydrochloride is a valid alternative for treating pathological anxiety in patients in which the state of alertness and good psychomotor skills must be preserved

Effects of a single administration of buspirone on catalepsy, yawning and stereotypy in rats

In the present study, the effects of a single administration of buspirone (0.1, 0.3, 1.0, and 3.0 mg/kg sc-30 min before testing) on three dopamine-related behaviors were evaluated in 4-month old male Wistar rats (7-10 animals per group). Buspirone decreased haloperidol (2.0 mg/kg ip)-induced catalepsy in a dose-dependent manner (from 7.30 to 5.09 1n of s compared to the untreated control group). Apomorphine (0.06 mg/kg sc)-induced yawning was also dose-dependently reduced (from 26.7 to 0.9 yawns in 30 min) and so was apomorphine (1.0 mg/kg sc)-induced stereotypy (from 32.9 to 5.9, sum of scores). The present results indicate that buspirone presents unique pharmacological effects related to dopaminergic transmission not only in biochemical but also in behavioral terms

Efeitos da buspirona e diazepam, puros ou em combinaçäo com álcool, no desempenho de habilidades e potencias evocados / Buspirone and diazepam effects alone or in association with the alcohol in abilities and e vocated menpowers

Os efeitos da buspirona 10 e 20 mg e diazepam 10 mg no desempenho de habilidades e me respostas evocadas, bem como suas interaçöes com álcool - 0.8 g/Kg, foram pesquisados em 24 homens saudáveis. O álcool causou o maior dano a atividade normal, seguido de perto pelo diazepam. Ambas as doses de buspirona causaram menores efeitos. A buspirona apresenta pricipalmente efeitos sedativos de menor duraçäo, ao passo que o diazepam prejudicou o senso de direçäo e o equilíbrio do corpo, além de ser sedativo. Ambos os ansiolíticos mostraram apenas leves interaçöes adicionais na presença da dose de álcool. Foram observados nos potenciais evocados um forte efeito das drogas, um menor, mas significativo efeito do álcool e de interaçäo droga/álcool. Os efeitos do dizepam nos potenciais evocados foram similares aos do álcool, ao passo que a buspirona em algumas circunstância pareceu reverter o efeito do álcool. A farmacocinética tanto buspirona quanto do diazepam näo foi significativamente afetada pela administraçäo de álcool. O perfil de efeitos colaterais psicomotores de uma dose ansiolítica única é preferivel ao de uma dose única de 10 mg de dizepam