Cardiovascular Effects of d-Tetrandrine

Intravenous injections of d-tetrandrine (3.12–12.5 mg/kg) produced dose-dependent hypotension and bradycardia in the anesthetized rhesus monkey. A high dose (25.0 mg/kg) caused irreversible cardio-vascular and respiratory depression and death. The cardio-depressant activity of d-tetrandrine was not altered by pretreatment with atropine and dl-propranolol intensified the effects. d-Tetrandrine was found to increase plasma histamine levels. Pretreatment with tripelennamine or compound 48/80 did not prevent the initial effects but a combination did attenuate the responses of the 12.5-mg/kg dose and prevented the lethal effects of the 25.0-mg/kg dose. Increasing the infusion time from 4 to 30 min also attenuated the initial cardiodepressor responses. d-Tetrandrine (3.12–25.0 mg/kg) exerted negative inotropic and chronotropic effects and reduced coronary perfusion pressure when administered to the isolated, blood-perfused dog heart. Thus, the hypotension induced by d-tetrandrine may be the result of nonspecific depression of myocardium and vascular smooth muscle and histamine release.