ON PHYSIOLOGICAL DISPOSITION AND POSSIBLE MECHANISM OF ANTIHYPERTENSIVE ACTION OF DEBRISOQUIN

After injection of debrisoquin into rats, the drug was rapidly taken up into several organs, especially the heart. The drug levels then declined rapidly in most tissues for about 4 hr, followed by a period of much slower decline. Low concentrations could be detected in several organs 16 hr after injection. By the use of radioactive debrisoquin, metabolic products of the drug could be found in the heart, liver and intestine 6 hr after drug injection, but at 16 hr, metabolic products were found only in the intestine, urine and feces. About two-thirds of the drug underwent biotransformation. Distinct adrenergic neuronal blocking action, as revealed by inhibition of the physostigmine-induced pressor response, persisted for only about 1 1 2 hr after injection of 5 mg kg of debrisoquin. This short duration of sympatholytic action in the face of prolonged antihypertensive action in man and the hypertensive rat, coupled with the finding that the low residual amounts of debrisoquin are sufficient to inhibit adrenergic neuronal monoamine oxidase (MAO), suggests that the antihypertensive action of debrisoquin and other neuronal blocking agents may lie, in part, in inhibition of neuronal MAO. © 1969.