PHARMACOLOGICAL STUDIES WITH GUANISOQUIN

¹ Departments of Pharmacology and Medicinal Chemistry, Medical Research Laboratories, Chas. Pfizer & Co., Inc., Groton, Connecticut

Guanisoquin was found to be an effective antihypertensive agent during chronic administration at 5 to 20 mg/kg orally to conscious hypertensive dogs. In normotensive dogs under sodium pentobarbital anesthesia, guanisoquin at 1 to 4 mg/kg i.v. increased blood pressure, heart rate and total peripheral resistance. Cardiac output was not significantly changed at 1 mg/kg i.v. It was increased at 4 mg/kg and was slightly lowered at 10 mg/kg i.v. Administration of guanisoquin into the common carotid artery of anesthetized dogs produced a pronounced lowering of blood pressure. Following intravenous administration at 1 to 10 mg/kg and intraarterial administration at 4 to 16 µg, guanisoquin increased femoral arterial blood flow in dogs. Pronounced depletion of norepinephrine was demonstrated in heart and aorta Of guinea pigs. In the cat nictitating membrane preparation, reduction of contractions produced by pre- and postganglionic stimulation of the cervical sympathetic chain was observed following guanisoquin at 1 to 10 mg/kg i.v. In respect to this sympathetic blocking action guanisoquin was only one-fourth as potent as guanethidine. Peripheral vascular activity of guanisoquin was indicated by antagonism of the epinephrine-and angiotensin-induced contractions of isolated rabbit aortic strips. Guanisoquin was found to be an effective local anesthetic in guinea pigs.

The hypotensive effect of guanisoquin was considered to be primarily due to catecholamine depletion and blockade of sympathetic transmission at the postganglionic level. Centrally mediated interference with vasomotor tone and peripheral vasodilation may also be partially responsible for guanisoquin-induced lowering of blood pressure.