PHARMACOLOGICAL ACTION OF OCTOPAMINE WITH SPECIAL REFERENCE TO BIOCHEMICAL CONVERSION TO NORADRENALINE

Abstract

Octopamine produced a transient rise of blood pressure in anesthetized dogs and the relative potency of octopamine to noradrenaline was approximately 1: 250. Treatment with reserpine of animals resulted in a marked reduction of the pressor action of octopamine, while it produced a potentiation of catecholamine action. The reduced response of reserpinized animals to octopamine was restored by an infusion of noradrenaline. The pressor action of octopamine was definitely potentiated by cocaine in normal as well as reserpinized animals. The pressor action of octopamine was blocked or reversed by tolazoline not only in normal but also in reserpinized animals. In the reserpinized spinal vagotomized preparation of dog, the relative potency in pressor action of octopamine to noradrenaline was approximately 1: 600. But the dose-response curve of octopamine was parallel to that of adrenaline rather than noradrenaline. Treatment with reserpine caused a marked decrease in the pressor action of tyramine in spinal vagotomized dogs. After a continuous infusion of 5 or 10 /[mu]g/kg/min of octopamine, there was a progressive increase in the pressor action of injected tyramine until 90 min. when a maximal restoration of tyramine response was attained. The infusion of noradrenaline at a rate of 0.01 or 0.02 [mu]g/kg/min., equipotent to the effective octopamine dose, for 2 hours did not increase the pressor action of tyramine. After an infusion of 10 [mu]g/kg/min of octopamine for 30 min., there was an about 2-fold potentiation of pressor action of injected noradrenaline. But no more potentiation was obtained during the further infusion of octopamine. The injection of octopamine produced a sustained contraction of the cat nictitating membrane, and increased the response to stimulation of the preganglionic sympathetic fibers. After the intravenous injection of octopamine, there were significant increases in catecholamine level at 30 min. in brain and at 5 min. in submaxillary gland, atria, spleen and adrenals. The elevation of amine level caused by ocotpamine was followed by significant decreases in all tissues except brain. The incubation of octopamine with the 9,500 x g supernate of rabbit liver resulted in a formation of noradrenaline. In contrast to the linear increase in formation of adrenaline from synephrine for 90 min., the formation of noradrenaline from octopamine reached a plateau as early as 5 min. after incubation. The intravenous injection of octopamine increased the catecholamine fluorescence in the submaxillary gland, atria and spleen of intact rats 15 min. later but decreased it 2 hr. later. The injection of octo-pamine to reserpine-treated rats made the fluorescence reappear in the trabecula of spleen 15 min. later. The sympathomimetic action of octopamine is discussed regarding direct alpha- and beta-actions on the adrenoceptive sites, indirect action due to release of noradrenaline and indirect action of noradrenaline converted from the octopamine taken up.