Modulation of beta-adrenergic receptors and calmodulin following acute and chronic treatment with neuroleptics

Abstract

Neuroleptic drugs have several acute and chronic actions on biochemical mechanisms of brain: (a) Acutely they block the action of catecholamines on the adrenergic receptor-adenylate cyclase complex, thereby preventing the catecholamine-induced rise in cyclic AMP. (b) With long-term treatment they appear to produce a compensatory induction of these adrenergic receptors. (c) Neuroleptics also bind to an endogenous calcium-dependent protein, termed calmodulin, whichis found in high concentrations in the CNS. This binding is relatively specific for clinically-effective neuroleptics of diverse chemical structure. (d) The binding of neuroleptics to calmodulin can explain several of their biochemical actions and suggests that some of the pharmacological and clinical effects of neuroleptics may also be explained by this same common mechanism.