Effects of alpha- and beta-adrenergic blockers on chlorpromazine-induced elevation of plasma glucose and cyclic AMP in fed mice.

Abstract

The subcutaneous administration of chlorpromazine (CPZ) caused a dose response increase in plasma glucose and cyclic AMP levels in fed male mice. Hexamethonium abolished the elevation of both plasma glucose and cyclic AMP. Propranolol did not inhibit the elevation of plasma glucose but inhibited the increase of plasma cyclic AMP. In contrast, phentolamine and yohimbine completely suppressed the elevation of plasma glucose but not that of plasma cyclic AMP. These results indicate that the hyperglycemia due to CPZ was mediated through the stimulation of alpha-adrenoceptor and on the contrary CPZ increased plasma cyclic AMP through the stimulation of beta-adrenoceptor and that the increase in plasma glucose induced by CPZ was independent of the activation of adenylate cyclase and the increased plasma cyclic AMP. In addition, in contrast to phentolamine and yohimbine, phenoxybenzamine was ineffective to prevent the hyperglycemia induced by CPZ. Moreover, a higher dose of dihydroergotamine was required to inhibit the hyperglycemia.