Abstract

DMI, N-(γ-methylaminopropyl-iminodibenzyl) hydrochloride, produced an increase in heart rate and cardiac force accompanied by inconstant changes in blood pressure both in chloralose-anesthetized, vagotomized dogs and the canine heart-lung preparation. Such cardiovascular activity was completely blocked by DCI or greatly diminished by guanethidine and in reserpine-pretreated animals. In addition, DMI potentiated the chronotropic, inotropic and pressor response to exogenous norepinephrine; did not modify the effects of epinephrine and isoproterenol; and decreased significantly the cardiac changes induced by stellate ganglion stimulation. The administration of DCI either prevented or reversed the pressor potentiation of norepinephrine by DMI. Moreover, when this latter catecholamine was enhanced in this effect by guanethidine, the administration of DMI did not affect further the dose-response curve. This held true when DMI was injected prior to guanethidine. It was also shown that DMI diminished the pressor response to carotid occlusion, and afterwards guanethidine was unable to modify this action in either sense. Conversely, DMI partially reversed the blockade of guanethidine on the response to carotid occlusion. Finally, this agent abolished the pressor and chronotropic effects of tyramine, while guanethidine only decreased them. With regard to tissue norepinephrine, 3 mg/kg of DMI inhibited significantly its depletion, induced by guanethidine, in the dog ventricle. A higher dose of DMI (12 mg/kg) prevented a similarly induced depletion in atria, ventricles and spleen of the rabbit.

It is concluded that DMI acts on the heart by releasing norepinephrine and producing specific supersensitivity to this catecholamine on its cardiac sites of action. The pressor potentiation of norepinephrine is due, mostly if not entirely, to cardiac action. Some evidence strongly suggests that DMI also blocks the release of norepinephrine induced by various procedures. Thus, this compound abolishes the cardiovascular effect of tyramine, diminishes the action of stellate ganglion stimulation and carotid occlusion, and, finally, antagonizes several pharmacological properties of guanethidine.