Monoamine oxidase inhibitors: effects on tryptophan concentrations in rat brain

It has been suggested that inhibition of tryptophan (Trp) pyrrolase and 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) inhibitors. The drugs studied during the course of the long-term (28 day) experiments were phenelzine, N2-acetylphenelzine, tranylcypromine, 4-fluorotranylcypromine, 4-methoxytranylcypromine and (-)-deprenyl. High-pressure liquid chromatography with electrochemical detection was employed to measure Trp levels in brains of both MAO inhibitor- and vehicle-treated animals. No significant increases in brain Trp levels were observed as a consequence of MAO inhibitor treatment. Acute time-response (up to 24 h) and dose-response studies were conducted following the administration of phenelzine and tranylcypromine. Only after administration of high doses of these drugs was an elevation in brain Trp observed and the increase was relatively short-lived. These results suggest that elevation of brain Trp may be an important factor in the actions of MAO inhibitors only at high doses of these drugs.