3,4-dimethoxyphenethylamine (DMPEA) and schizophrenia.
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A method was developed for the separation by thin-layer chromatography of 14C-labelled 3-methoxy, 4-hydroxyphenethylamine, 3-hydroxy, 4-methoxyphenethylamine and 3,4-dimethoxyphenethylamine (DMPEA) after incubation of dopamine with catechol-O-methyltransferase (COMT) in lysates of human red blood cells (RBC). 14 C-methyl-S-adenosyl-menthionine was used as the methyl donor. Total COMT activity with noradrenaline or dopamine as substrates, respectively, and the pattern of 14C-methylated metabolites of dopamine were measured in RBC of 47 schizophrenic patients and in 34 control subjects. There were no differences between patients and controls. DMPEA was not formed by RBC in schizophrenic patients (or in controls), a finding which argues against the "pnk spot"/DMPEA hypothesis of schizophrenia. The methods used seem suitable for studies of other human disorders where COMT might be involved.
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Some reports have suggested that methylation and demethylation of compounds related to 6-hydroxydopamine may be involved in endogenous mental disorder. We report the synthesis of 3,4-dimethoxyphenethylamine (DMPEA) and 2,4,5-trimethoxyphenylisopropylamine (TMA-2) with each methoxyl group separately labeled with 14C. The rate and percent demethylation of these two compounds, with five labeled positions, were determined in the rat. The results suggest that TMA-2 might be metabolized to a hydroquinone in vivo; a similar metabolic intermediate of the psychoactive compound DOM is known to give rise in vitro to an indole.