Effect of narcotic analgesics on plasma cyclic AMP levels in male mice

Abstract

Systemic administration of morphine, as well as pethidine and pentazocine, increased plasma cyclic AMP levels in male mice. Intracerebroventricular administration of morphine and β-endorphin also increased plasma cyclic AMP levels. The effect of morphine and β-endorphin was antagonized by naloxone indicating the involvement of opiate receptors in the central nervous system for the effect of morphine on cyclic AMP levels. Tolerance was shown to develop to the action of morphine in increasing the plasma cyclic AMP. The morphine-induced increase in plasma cyclic AMP was abolished by treatment with propranolol or pentolinium or by adrenalectomy but not by treatment with atropine, phentolamine, 6-hydroxydopamine or α-methyltyrosine. These findings suggest that morphine increases plasma cyclic AMP levels mainly by releasing catecholamines, from the adrenal medulla, and these activate adenylate cyclase via the stimulation of β-adrenoceptors.