Mechanism of the hypotensive effect of intravenous methaqualone in the cat

Abstract

Methaqualone, a non-barbiturate hypnotic, has been reported to produce hypotension in animals. Experiments were undertaken to evaluate the mechanisms responsible for this effect. In chloralose-anesthetized cats, iv administration of 0.5 to 10.0 mg/kg of methaqualone produced dose-dependent decreases in blood pressure. The hypotension was associated with decreases in contractile force and heart rate at doses of 1 mg/kg or higher. Pretreatment with atropine or bilateral vagal nerve section did not influence these cardiovascular effects. In vagotomized cats: (1) spinal section markedly reduced the depressant effects of methaqualone on blood pressure, contractile force and heart rate and (2) removal of the stellate ganglia reduced the negative inotropic and chronotropic effects of the drug. Furthermore, administration of methaqualone (31.2–500 μg/kg) into a vertebral artery of vagotomized cats produced dose-dependent decreases in blood pressure, contractile force and heart rate. In the isolated cat hindquarters preparation perfused at constant blood flow, methaqualone (31.2–1000 μg) produced transient decreases in perfusion pressure which were not altered by pretreatment with phentolamine, propranolol, atropine or tripelennamine. In the rabbit perfused isolated heart, large doses of drug (0.25 to 2.0 mg) were required to depress contractile force. These results indicate that hypotension produced by iv methaqualone results primarily from a centrally mediated depression of sympathetic neural outflow to the heart and vasculature and, to a lesser extent, from direct relaxation of vascular smooth muscle and direct myocardial depression.