Pharmacodynamics of minaxolone, a new steroidal anesthetic.

Studies were designed to examine blood concentration-response relationships for minaxolone administered to sheep by either i.v. infusion or bolus injection in both clinical doses and overdoses. Responses examined included effects on sensory nervous, cardiovascular and respiratory systems. The ratio of fatal blood concentrations to anesthetic blood concentrations (therapeutic ratio) was 3 to 4 without respiratory support other than endotracheal intubation to maintain a patent airway. Minaxolone consistently depressed respiration rate, raised PACO2 and depressed PAO2. Death resulted from respiratory failure. With intermittent positive pressure ventilation, the therapeutic ratio was raised to 30 to 40. Duration of anesthesia after bolus doses was directly related to the logarithm of the dose. Cardiovascular effects were minimal with clinical doses and mild overdoses and included slight tachycardia, slightly elevated blood pressure and increased total peripheral resistance with little or no change in cardiac output. With gross overdoses, stable hypotension and depressed cardiac output resulting from decreased stroke volume occurred. Its excellent anesthetic properties and lack of deleterious effects at normal doses on the cardiovascular system commend minaxolone for further evaluation.