EVIDENCE THAT 5‐METHOXY‐N, N‐DIMETHYL TRYPTAMINE IS A SPECIFIC SUBSTRATE FOR MAO‐A IN THE RAT: IMPLICATIONS FOR THE INDOLEAMINE DEPENDENT BEHAVIOURAL SYNDROME

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Abstract
—: A simple method for the separation of 5‐hydroxyindoleacetic acid (5‐HIAA) and 5‐methoxyindoleacetic acid (5‐MeOIAA) on columns of non‐ionic polystyrene (Amberlite XAD‐2) is described. Administration of 5‐methoxy‐N, N‐dimethyl‐tryptamine (5‐MeODMT) 2 mg/kg i. p. to rats results in a sixfold increase in brain 5‐MeOIAA within 15 min. This increase is blocked by the selective inhibitor of MAO‐A, clorgyline, but not by the selective inhibitor of MAO‐B, deprenyl, indicating that 5‐MeODMT is deaminated almost entirely by MAO‐A. The apparent 5‐MeOIAA concentration in the brains of L‐tryptophan loaded rats is not reduced by clorgyline and deprenyl, either singly or in combination, indicating that most of this fluorescence is due to other, unidentified substances. The apparent concentration of 5‐HIAA in rat brain, minus 5‐MeOIAA, is unaffected by deprenyl and reduced by clorgyline. However, clorgyline and deprenyl in combination reduced 5‐HIAA values below those obtained with clorgyline alone. It is concluded that very little 5‐MeODMT or other 5‐methoxyindoleamines are formed endogenously in rat brain, and that the stereotyped syndrome of hyperactivity and tremors produced in rats by pretreatment with MAO inhibitors and L‐tryptophan is dependent on the formation of an N‐substituted derivative of 5‐HT which is at least partly deaminated by MAO‐B to 5‐HIAA.