MONOAMINE-OXIDASE INHIBITORS - EFFECTS ON TRYPTOPHAN CONCENTRATIONS IN RAT-BRAIN

It has been suggested that inhibition of tryptophan (Trp) pyrrolase an d a subsequent elevation of brain Trp may contribute to the actions of antidepressant drugs. In our laboratories, we have conducted a series of experiments measuring brain Trp levels in the rat after both acute and chronic administration of several monoamine oxidase (MAO) inhibit ors. The drugs studied during the course of the long-term (28 day) exp eriments were phenelzine, N-2-acetylphenelzine, tranylcypromine, 4-flu orotranylcypromine, 4-methoxytranylcypromine and(-)-deprenyl. High-pre ssure liquid chromatography with electrochemical detection was employe d to measure Trp levels in brains of both MAO inhibitor- and vehicle-t reated animals. No significant increases in brain Trp levels were obse rved as a consequence of MAO inhibitor treatment. Acute time-response (up to 24 h) and dose-response studies were conducted following the ad ministration of phenelzine and tranylcypromine. Only after administrat ion of high doses of these drugs was an elevation in brain Trp observe d and the increase was relatively short-lived. These results suggest t hat elevation of brain Trp may be an important factor in the actions o f MAO inhibitors only at high doses of these drugs.