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Tricyclic and Monoamine Oxidase Inhibitor Antidepressants: Structure-Activity Relationships

  • Chapter
Handbook of Psychopharmacology

Abstract

Tricyclic and monoamine oxidase inhibitor (MAOI) antidepressants are the two classes of drugs most frequently used in the treatment of moderate to severe depression. Their efficacy in depression has been known for nearly two decades (Crane, 1957; Loomer et al., 1957; Kuhn, 1958). The tricyclic inhibitors tend to increase concentrations of certain biogenic amines in synaptic clefts in peripheral organs and brain by preventing their reuptake into the nerve endings from which they were secreted. MAOIs block the catabolism of biogenic amines within presynaptic nerve terminals, and thus provide that greater amounts of these transmitters accumulate within nerve terminals and are released into the synaptic cleft. Therefore, both drug classes can be expected to accomplish a similar effect-an increase in amine concentration in the synaptic cleft and a consequent greater excitation of postsynaptic receptors. This common effect of MAOIs and of tricyclic antidepressants as exerted in brain is generally considered to be the basis for their antidepressant activities. The antidepressant actions of imipramine and iproniazid in man, and their effectiveness as antagonists of the sedation produced in animals by reserpine-induced depletion of brain biogenic amines, contributed early to the formulation of the amine hypothesis of affective disorders (Schildkraut, 1965, 1969; Schild kraut and Kety, 1967).

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  1. Department of Pharmacology, Wellcome Research Laboratories, Burroughs Wellcome Co., Research Triangle Park, North Carolina, USA

    Robert A. Maxwell & Helen L. White

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  1. Robert A. Maxwell
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  1. Department of Pharmacology, University of Cambridge, UK

    Leslie L. Iversen

  2. Department of Psychology, University of Cambridge, UK

    Susan D. Iversen

  3. Departments of Pharmacology and Psychiatry, The Johns Hopkins University School of Medicine, USA

    Solomon H. Snyder

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Maxwell, R.A., White, H.L. (1987). Tricyclic and Monoamine Oxidase Inhibitor Antidepressants: Structure-Activity Relationships. In: Iversen, L.L., Iversen, S.D., Snyder, S.H. (eds) Handbook of Psychopharmacology. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-4045-4_3

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