Behavioral, Metabolic, and Enzymatic Studies of a Brain Indoleethylamine N-Methylating System
Although there have been many good reasons to look for a brain indoleamine N-methylating enzyme since the introduction of the Harley-Mason amine methylation hypothesis of schizophrenia (Osmond and Smythies 1952) and Axelrod’s exciting and systematic elucidation of various amine-methylating enzymes in the central nervous system (Axelrod 1965), our own particular interests in this field started in 1964 when we were studying the effect of the intravenous infusion of various amine precursors on sleep patterns in man. We reported a 5-hydroxytryptophan (5-HTP)-induced increase in rapid eye movement sleep (Mandell, Mandell, and Jacobson 1965). At the same time we noted that occasionally there was a disruption of sleep during 5-HTP infusions, with episodes of bizarre mentation. Whereas 5-hydroxytryptophan alone in small doses (150 mg i.v. over 6 to 8 hours) would usually produce some degree of sedation in our subjects, higher doses (200 mg or more), or smaller doses given in combination with a monoamine oxidase inhibitor as a pretreatment before intravenous amino acid load produced behavioral and psychic activation. We then became aware of the wide variety of studies by a number of investigators (Kety 1961; Pollin, Cardon, and Kety 1961; Kline, Simpson, and Sacks 1967; Himwich et al. 1970) that demonstrated similar reversals of the indoleamino acid-produced sedation with monoamine oxidase inhibitor pretreatment.
KeywordsMonoamine Oxidase Monoamine Oxidase Inhibitor Isoamyl Alcohol Chick Brain Sheep Brain
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