Effects of some antipsychotic drugs on cardiovascular catecholamine receptors in the rat.

Abstract

1. Experiments were performed to determine the activity of four antipsychotic drugs on several catecholamine receptors that control the sympathetic cardiovascular responses in rats. 2. Chlorpromazine, thioridazine (0.03 and 0.1 mg kg-1) and haloperidol (0.3 and 1 mg kg-1) inhibited methoxamine-induced diastolic blood pressure increases in the pithed rat, whereas sulpiride (1 and 3 mg kg-1) was without effect. 3. Only sulpiride (3 mg kg-1) antagonized the pressor responses induced by xylazine. 4. Xylazine inhibited the heart rate increase induced by electrical stimulation of the spinal cord (C7-Th1) in the pithed rat. This effect was partially prevented by sulpiride (1 and 3 mg kg-1) and chlorpromazine (0.3 mg kg-1). A higher dose of chlorpromazine (1 mg kg-1) abolished the inhibitory effect of xylazine. 5. Apomorphine infusion inhibited the pressor responses induced by electrical stimulation (Th5-L4) in pithed rats. This effect was reversed by sulpiride (0.01, 0.03 and 0.1 mg kg-1) and partially antagonized by haloperidol (0.1 mg kg-1). 6. The depressor response to fenoldopam in anaesthetized rats was only inhibited by the higher dose of chlorpromazine and thioridazine (3 mg kg-1). 7. Our results suggest that, in the peripheral nervous system of the rat, haloperidol and sulpiride act as antagonists of DA2 receptors while chlorpromazine and thioridazine antagonized DA1 receptors. Furthermore, thioridazine and haloperidol show alpha 1-adrenoreceptor antagonist properties, whereas sulpiride antagonizes alpha 2-adrenoreceptors. Chlorpromazine shows mixed alpha 1/alpha 2-adrenoreceptor antagonism.