Interaction in the cerebral metabolism of the biogenic amines. Effects of phenelzine on the cerebral metabolism of the 5-hydroxyindoles in dog brain.

1. Chronic administration of phenelzine to dogs caused 5-hydroxyindol-3-ylacetic acid (5-HIAA) concentrations in c.s.f. from the lateral ventricle to be maintained at 50% of their normal values, but did not alter the concentrations of 5-HIAA in c.s.f. from the cisterna magna.2. Following 10 days treatment with phenelzine, the active transport of 5-HIAA from c.s.f. which normally occurs in the region of the fourth ventricle, was inhibited. This transport system was also inhibited by the addition of phenylacetic acid, the acid metabolite of phenelzine, to the fluid perfusing the cerebral ventricles.3. After 10-12 days treatment with phenelzine all regions of brain showed concentration increases to approximately 300% for 5-HT and 150% for 5-HIAA, but no alteration in the tryptophan concentration.4. Intravenous administration of tryptophan to dogs pretreated with phenelzine caused large increases in the concentration of tryptophan in brain and body fluids but did not alter either the concentrations of 5-hydroxytryptamine and 5-HIAA in brain or of 5-HIAA in c.s.f.5. A model of the cerebral metabolism of 5-hydroxytryptamine is proposed and the results are interpreted to mean that phenelzine has inhibitory actions, either directly or in some instances indirectly, on intracerebral tryptophan 5-hydroxylase, monoamine oxidase and the transport of 5-HIAA from both brain and c.s.f.