Detection of Psychotomimetic N,N-Dimethylated Indoleamines in the Urine of Four Schizophrenic Patients

Abstract

Pollin, Cardon and Kety (18) investigated the effects of large doses of various amino acids in combination with a monoamine oxidase (MAO) inhibitor on the behaviour of schizophrenics. They found that methionine in the presence of such an inhibitor was capable of producing behavioural changes which may ‘represent a biochemically induced acute flare-up of a chronic schizophrenic process on the one hand, or a toxic delirium superimposed upon chronic schizophrenia on the other’. Brune and Himwich (8) confirmed the clinical results of Pollin et al. On the basis of their previous work indicating that tryptamine appeared in increased concentrations in the urine before and during the activation of psychotic symptoms, they suggested that under loading conditions the formation of various N,N-dimethylated indoleamines might be facilitated in the body. The tertiary indoleamines so formed might mediate the psychotic effect of methionine with a MAO inhibitor on schizophrenic patients.

A Review of Nicotinic Acid, N-Methylated Indoleamines and Schizophrenia

“…They noted exacerbation of psychotic symptoms 2 weeks after the increase in bufotenine. Tanimukai et al (1970) and Narasimhachari et al (1971a) have replicated these findings with cysteine and MAOI. Using more specific assaying techniques they found both bufotenine and DMT in the urine of schizophrenics about 2 weeks before the major exacerbation.…”

“…Using more refined methods including gas-liquid chromatography, Tanimukai et al (1970) and Narasimhachari et al (1972) found bufotenine in the urine of schizophrenics given an MAOI and cysteine. Narasimhachari et al (1974) used gas chromatographic mass spectrometric methods to identify bufo tenine in chronic schizophrenics.…”

Further Studies on the Mode of Action of Psychotomimetic Drugs: Antagonism of the Excitatory Actions of 5‐hydroxytryptamine by Methylated Derivatives of Tryptamine

“…DMT, bufotenine and 5-MeODMT have been detected in higher levels in blood and urine samples from cases of acute schizophrenia than in samples from non-schizophrenics or chronic schizophrenics (Fischer & Spatz, 1970;Tanimukai, Ginther, Spaide, Bueno & Himwich, 1970; Narasimhachari, Heller, Spaide, Haskovec, Fujimori, Tabushi & Himwich, 1971;Narasimhachari, Heller, Spaide, Haskovec, Meltzer, Strahilevitz & Himwich, 1971). An enzyme capable of synthesizing N,N-dimethylated tryptamines from tryptamine or 5-HT has been demonstrated in rat brain and in human brain (Mandell, Buckingham & Segal, 1971;Saavedra & Axelrod, 1972); the O-methylation of 5-hydroxytryptamine in the pineal body is well known (Axelrod & Weissbach, 1961), and recently, Green, Koslow & Costa (1973) demonstrated the presence in rat hypothalamus of 5-MeOT, apparently originating outside the pineal, since pinealectomy had little effect on the brain concentrations.…”

Urinary Excretion of N,N-Dimethylated Tryptamines in Chronic Schizophrenia: A Review of the Present Status of the Hypothesis

“…The compounds were claimed to be present in the urines of four out of six schizophrenic middle-aged male patients on a regular diet without the benefit of an MAOI drug (26) and in two children with infantile autism and two drug-free schizophrenic adults (27) and also in two out of four middle-aged chronic schizophrenic patients. These latter patients were free of psychotropic drugs and were examined during the exhibition of an MAOI drug, or L-cysteine, or a combination of these (36). DMT was also found (22) in the urine of two male chronic schizophrenic patients, aged 57 and 60 as opposed to its absence in the urine of six stable young men.…”