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Behavioral, Metabolic, and Enzymatic Studies of a Brain Indoleethylamine N-Methylating System

  • Arnold J. Mandell
  • Bruce Buckingham
  • David Segal
Part of the Advances in Behavioral Biology book series (ABBI, volume 1)

Abstract

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.

Keywords

Monoamine Oxidase Monoamine Oxidase Inhibitor Isoamyl Alcohol Chick Brain Sheep Brain 
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References

  1. Axelrod, J. 1961. Enzymatic formation of psychotomimetic metabolites from normally occurring compounds. Science 134:343.PubMedCrossRefGoogle Scholar
  2. Axelrod, J. 1965. The formation and metabolism of physiologically active compounds by N and O methyl transferases. In Transmethyla-tion and Methionine Biosynthesis. S. K. Shapiro and F. Schlenk. Chicago: University of Chicago Press, p. 71.Google Scholar
  3. Blaschko, H., and Levine, W. G. 1966. Metabolism of indolealkyl-amines. In 5-Hydroxytryptamine and Related Indolealkylamines. V. Erspamer (ed.). New York: Springer-Verlag.Google Scholar
  4. Gessner, P. K.; Khairallah, P. A.; McIsaac, W. M.; and Page, I. H. 1960. The relationship between the metabolic fate and pharmacological actions of serotonin, bufotenine and psilocybin. J. Pharmacol. Exp. Ther. 130:126.PubMedGoogle Scholar
  5. Himwich, H. 1969. Personal communication.Google Scholar
  6. Himwich, H. E.; Narasimachari, N.; Heller, B.; Spaide, J.; Haskovec, L.; Fujimori, M.; and Tabushi, K. 1970. Comparative behavioral and urinary studies on schizophrenics and normal controls. In Biochemistry of Brain and Behavior. R. E. Bowman and S. P. Datta. New York: Plenum Press, p. 207.CrossRefGoogle Scholar
  7. Ichiyama, A.; Nakamura, S.; Nishizuka, Y.; and Hayaishi, O. 1970. Enzymic studies on the biosynthesis of serotonin in mammalian brain. J. Biol. Chem. 245:1699.PubMedGoogle Scholar
  8. Kety, S. S. 1961. Possible relation of central amines to behavior in schizophrenic patients. Fed. Proc. 20:4.Google Scholar
  9. Kline, N. S.; Simpson, G.; and Sacks, W. 1967. Amines and amine precursors combined with a monoamine oxidase inhibitor in the treatment of depression. In Neuropsychopharmacology. New York: Excerpta Medica Foundation, p. 343.Google Scholar
  10. Mandell, A. J. 1970. Drug induced alterations in brain biosynthetic enzyme activity—a model for adaptation to the environment by the central nervous system. In Biochemistry of Brain and Behavior. R. E. Bowman and S. P. Datta (eds.). New York: Plenum Press, p. 97.CrossRefGoogle Scholar
  11. Mandell, M.; Mandell, A. J.; and Jacobson, A. 1965. Biochemical and neurophysiological studies of paradoxical sleep. In Recent Advances in Biological Psychiatry, vol. VII. J. Wortis (ed.). New York: Plenum Press, p. 115.Google Scholar
  12. Mandell, A. J., and Spooner, C. E. 1969. An N,N-indole transmethy-lation theory of the mechanism of MAOI-indole amino acid load behavioral activation. In Schizophrenia—Current Concepts and Research. D. V. Sankar (ed.). New York: PJD Pub., p. 496.Google Scholar
  13. Morgan, M., and Mandell, M. 1969. Indole(ethyl) amine N-methyltrans-ferase in the brain. Science 165:492.PubMedCrossRefGoogle Scholar
  14. Osmond. H. and Smythies. J. R. 1952. Schizophrenia. A new approach. J. Mental Sci. 98:309.Google Scholar
  15. Pollin, W.; Cardon, P. V.; and Kety, S. S. 1961. Effects of amino acid feedings in schizophrenic patients treated with iproniazid. Science 133:104.PubMedCrossRefGoogle Scholar
  16. Segal, D. S., and Mandell, A. J. 1970. Behavioral activation of rats during intraventricular infusion of norepinephrine. Proc. Nat. Acad. Sci. U.S.A. 66:289.CrossRefGoogle Scholar
  17. Turner, W. J., and Merlis, S. 1959. Effect of some indolealkyl-amines in man. Arch. Neurol. Psychiat. 81:121.Google Scholar

Copyright information

© Plenum Press, New York 1971

Authors and Affiliations

  • Arnold J. Mandell
    • 1
  • Bruce Buckingham
    • 1
  • David Segal
    • 1
  1. 1.School of MedicineUniversity of CaliforniaSan Diego, La JollaUSA

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