Selective monoamine oxidase inhibitor drugs as aids in evaluating the role of type A and B enzymes

Abstract

The ability of type A monoamine oxidase (MAO) inhibitor drugs (clorgyline, Lilly 51641 and harmaline) and type B MAO inhibitor drugs ((−)-deprenyl and pargyline) to alter the pharmacology of reserpine was evaluated in rats. The administration of type A inhibitors prevented motor depression and palpebral ptosis following reserpine administration, while type B inhibitors were ineffective unless given in doses large enough to block both A and B enzymes. When administered alone all of the MAO inhibitors induced hypothermia, while reserpine alone induced hyperthermia. Type A drugs prevented the hyperthermia induced by reserpine but type B drugs were inactive. Type A drugs, however, when given in doses high enough to block both enzymes were unable to prevent reserpine-induced hyperthermia. From these observations we postulate: (1) reserpine depletes an endogenous amine that is metabolized by type A enzyme and the absence of this amine results in motor depression and palpebral ptosis; (2) the ability of all the MAO inhibitors tested to induce hypothermia when administered alone is probably the result of preventing the inactivation of an amine that is metabolized by either MAO; and (3) the ability of drugs that block type A enzyme to prevent the hyperthermia induced by reserpine is probably the result of the accumulation of an amine that is inactivated by type A MAO.