MECHANISM OF HYPOTENSIVE ACTION OF MEBUTAMATE

¹ Departments of Pharmacology and Anesthesiology, College of Physicians and Surgeons, Columbia University, New York, N. Y.

The mechanism of the hypotensive action of mebutamate was investigated in cross-circulation experiments in anesthetized dogs. Pressor responses were elicited in the recipient’s body by electrical stimulation of the medullary vasomotor center of the vascularly isolated head. These pressor responses were not modified when mebutamate, 20 mg/kg, i.v., was given to the donor dog, but were markedly reduced when the agent was similarly given to the recipient’s body circulation. In anesthetized cats mebutamate often reduced the resting splanchnic nerve activity and the discharge evoked by vasomotor center stimulation. In addition, mebutamate exhibited a moderate blocking action on the autonomic ganglia. Intraarterial injections of mebutamate, 2 mg, in dogs also caused a prompt and marked increase in femoral arterial blood flow, unaffected by chronic sympathectomy or administration of atropine and/or pronethalol. The hypotensive action of mebutamate is thus attributed to both a direct vasodilator effect and an inhibition of the sympathetic vasomotor outflow. The former appears to be responsible for the initial, transient and prompt fall in the blood pressure, and the latter for the sustained vasomotor depression essentially at the spinal and ganglionic sites.