Theoretical and therapeutic potential of indolamine precursors in affective disorders

The strategy of loading with precursor amino acids of the monoamines postulated to be involved in the affective disorders is reviewed. Phenylalanine, tyrosine, L-dopa, L-tryptophan and L-5-hydroxytryptophan (L-5HTP) have been found to induce differential behavioral and biochemical effects in both healthy subjects and endogenous depressives. Indoleamine precursors predominantly cause mood changes. However, the efficacy of these amino acids as antidepressants has been neither clearly established nor refuted, probably due to insufficient consideration of the following criteria; sufficiently high plasma levels to be taken up into the brain, effective stimulation of serotoninergic systems, and selective increase of serotonin turnover with minimal interaction with other neurotransmitters. The use of intravenous L-5HTP as a provocative test in depressive patients, with concomitant neuroendocrinological and psychometric measurements, may be a method adequately fulfilling these requirements.