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.
KeywordsLarge Neutral Amino Acid Plasma Tryptophan Bioi Psychiatry Brain Tryptophan Monamine Oxidase
Unable to display preview. Download preview PDF.
- Baker GB, Dewhurst WG (1985) Biochemical theories of affective disorders. In: Dewhurst WG, Baker GB (eds) The pharmacotherapy of affective disorders: theory and practice. Croom Helm, London, pp 1–59.Google Scholar
- Campbell IC, Colburn R, Walker MN, Lovenberg W, Murphy DL (1978) Norepine-phrine and serotonin metabolism in the rat brain: effects of chronic phenelzine administration. In: Deniker P, Radouco-Thomas C, Villeneuve A, Baronet-Lacroix D, Garcin F (eds) Neuropsychopharmacology, vol 1. Pergamon Press, Oxford.Google Scholar
- Møller SE, de Beurs P, Timmerman L, Tan BK, Leijnse-Ybema HJ, Cohen Stewart MH, Hopfner Petersen HE (1986) Plasma tryptophan and tyrosine ratios to competing amino acids in relation to antidepressant response to citalopram and maprot-iline. A preliminary study. Psychopharmacology 88: 96–100.PubMedCrossRefGoogle Scholar
- van Praag HM (1984a) Depression, suicide and serotonin metabolism in the brain. In: Post RM, Ballenger JC (eds) Neurobiology of mood disorders. Williams & Wilkins, Baltimore, pp 601–608.Google Scholar
- Walinder J, Carlsson A, Persson R, Wallin L (1980) Potentiation of the effect of antidepressant drugs by tryptophan. Acta Psychiatr Scand 28: 243–249.Google Scholar
- Young SN (1984) Monoamine precursors in the affective disorders. In: Burrows GD, Werry JW (eds) Advances in human psychopharmacology, vol 3. JAI Press, Greenwich, CT, pp 251–285.Google Scholar
- Young SN (1991) Use of tryptophan in combination with other antidepressant treatments: a review. J Psychiatr Neurosci 16: 241–246.Google Scholar
- Yu PH, Boulton AA (1992) A comparison of the effect of brofaromine, phenelzine and tranylcypromine on the activities of some enzymes involved in the metabolism of different neurotransmitters. Res Commun Pyschol Psychiat Behav 16: 141–153.Google Scholar