Acute and chronic toxicity of oxethazaine: A highly potent local anesthetic☆

Abstract Oxethazaine, an N -substituted bis-acetamide, represents a new series of powerful local anesthetics exceeding by far the potency of either cocaine, procaine, lidocaine, or dibucaine. Acute toxicity studies establish that it is not a primary skin irritant; neither does it cause corneal damage nor conjunctival erythema and hyperemia. Further, there is a considerable margin of safety for intragastric, subcutaneous, intramuscular, intrarectal and intravesical administration. Toxicity following intravenous and intrapulmonary administration, however, is high, and deaths occur quickly from depression of myocardial contractility and impaired conduction. Rats and dogs can ingest oxethazaine daily for months without evidence of either toxicity, effect on weight, peripheral blood picture, bone marrow, viscera or kidney, and liver function. The tendency for increased deposition of glycogen in the liver is probably a reversible storage phenomenon. Absorption of intragastrically administered oxethazaine in water or alumina gel occurs rapidly and is detectable within 30 minutes. The amounts absorbed, however, differ and are greater from the water vehicle. Detoxication probably is chiefly in the liver and involves the metabolism of hydroxyethylamine and mephentermine.