The effects of chlorpromazine and haloperidol on second messenger systems related to adrenergic receptors

The aim of this study was to investigate the binding of chlorpromazine and haloperidol to rat cerebral cortical adrenoceptors and to assess their effect on responsiveness of alpha 1- and beta-adrenoceptors measured by accumulation of second messengers, inositol phosphate and cyclic AMP, after stimulation with noradrenaline and isoproterenol. The effect of neuroleptics on protein kinase C was assessed by carrying out incubations in the absence and presence of the phorbol ester, 12-O-tetradecanoyl-phorbol 13-acetate (TPA). The effects of chronic administration of haloperidol (0.5 mg/kg/d for 14 days) on responses of second messenger systems to noradrenaline and isoproterenol in the presence and absence of TPA were also measured. The results indicate that in vitro chlorpromazine and haloperidol similarly inhibit noradrenaline-induced responses of inositol phosphate and cyclic AMP, but differently affect the potentiation of these responses by protein kinase C: the inhibitory effect of haloperidol, but not that of chlorpromazine was prevented by TPA. Similarly, only chlorpromazine inhibited the cyclic AMP responses to isoproterenol. The differences between the effects of chlorpromazine and haloperidol may be explained by their different affinity to various subtypes of adrenoceptor. In a chronic experiment haloperidol did not induce changes in responsiveness of cortical alpha 1- and beta-adrenoceptors, but inhibited TPA-induced potentiation of cyclic AMP responses.