LACK OF ENHANCEMENT OF DIMETHYLTRYPTAMINE FORMATION IN RAT BRAIN AND RABBIT LUNG IN VIVO BY METHIONINE OR S‐ADENOSYLMETHIONINE

Abstract
In vivo conversion of intracisternally administered [14C]tryptamine to [14C]N,N‐dimethyl‐tryptamine (DMT) in rat brain, even in the presence of an excess of substrate and methyl donor appeared to be insignificant, although enzymatically synthesized [14C]DMT was recovered readily after intracranial injection. Authenticity of [14C]DMT was demonstrated by cocrystallization with authentic DMT and oxalic acid to constant specific radioactivity after chromatographic separation of [14C]DMT. In rabbit lung, the apparent Km for S‐adenosylmcthionine (SAMe) (29 μM) with indolethylamine‐N‐methyltransferase was found to be close to endogenous levels of SAMe (34 μM) that are not likely to saturate the enzyme normally. Nevertheless. large doses of L‐methioninc or SAMe failed to increase the in vivo conversion of [14C]N‐methyltryptamine to [14C]DMT in this tissue. The production of [14]DMT was instead markedly irihihitrd by this treatment. possibly due to an effect of S‐adeno‐sylhomocysteine. Our results fail to support the hypothesis that psychotropic effects of methionine or SAMe are due to increased accumulations of pharmacologically active methylated indoleamines.