Cardiac Actions of Methoxamine

With Special Reference to Its Antagonistic Action to Epinephrine

¹ the Department of Pharmacology, Faculty of Medicine, University of Tokyo, and Iatrochemical Institute of the Pharmacological Research Foundation, Tokyo, Japan
² From the Department of Pharmacology, Faculty of Medicine, University of Tokyo, and Iatrochemical Institute of the Pharmacological Research Foundation, Tokyo, Japan

The cardiac action of large doses of methoxamine and its antagonistic action to epinephrine were studied, using a dog heart-lung preparation. In doses of 4 mg. and above, methoxamine showed a marked negative inotropic action, while it produced only a slight decrease in the heart rate. Pretreatment of animals with 0.1 mg./Kg. of reserpine did not modify the inotropic action, but the decrease in the heart rate disappeared. Simultaneous with these changes, a decrease in the coronary flow and a rise of the pulmonary arterial pressure were observed. Methoxamine in doses of 1 mg. and more abolished both the positive inotropic and the positive chronotropic actions of epinephrine. The negative inotropic action of methoxamine was ascribed to a nonspecific, as yet undetermined mechanism, and the antagonistic action was ascribed to the competitive antagonism at the receptor site (thus methoxamine may be looked upon as a blocking agent of adrenergic receptor). The weak negative chronotropic action was taken to be an expression of the blockade of the humoral effects of the intrinsic sympathomimetic amines.

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