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Differential behavioural and biochemical effects on the central nervous system by cycloserine isomers

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Summary

Clinical observations of the tranquillizing and antidepressant effects of l- and dl-isomers were subjected to a biochemical and pharmacological analysis and compared with the effect of d-Cs. From pharmacological and biochemical experiments on animals it appears that the action of l-Cs resembles most closely the thymoleptic effect of imipramine: a strong antireserpine effect, slight stimulation of MAO activity in the brain and a mild inhibitory effect of MAO activity in the liver in vivo. It does not inhibit markedly tryptamine convulsions. The d-form lacks, contrary to imipramine, the antireserpine effect. It stimulates MAO activity in brain but does not influence MAO in the liver. In keeping with the stimulating action as regards MAO activity in the brain it markedly inhibits tryptamine convulsions. Dl-Cs on the one hand has in common with imipramine the antireserpine effect, on the other hand, it markedly inhibits MAO in the liver and at the same time mildly stimulates MAO in the brain.

In trials with the administration of a single large dose of Cs to volunteers all three forms of Cs, in the first place, increased IAA excretion and had a slighter effect on 5-HIAA excretion; the smallest increase occurred in kynurenine excretion.

These findings support the original hypothesis of the relationship between the central effect of Cs and the interference with the serotonin and tryptamine metabolism and possibly with their distribution and storage.

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Author notes

  1. Vladimír Vítek

    Present address: Research Facility, Rockland State Hospital, Orangeburg, N.Y., USA

Authors and Affiliations

  1. Research Institute for Experimental Therapy, Medical Clinic of Postgraduate Medical Institute, Prague-Krč

    Vladimír Vítek, Konrád Ryšánek, Zdeňka Horáková, Jitka Muratová, Miloš Vojtěchovský & Radek Vejdovský

  2. Research Institute for Pharmacy and Biochemistry, Prague

    Vladimír Vítek, Konrád Ryšánek, Zdeňka Horáková, Jitka Muratová, Miloš Vojtěchovský & Radek Vejdovský

  3. Institute of Human Nutrition, Prague

    Vladimír Vítek, Konrád Ryšánek, Zdeňka Horáková, Jitka Muratová, Miloš Vojtěchovský & Radek Vejdovský

  4. Tuberculosis Department of Thomayer Hospital, Prague-Krč

    Vladimír Vítek, Konrád Ryšánek, Zdeňka Horáková, Jitka Muratová, Miloš Vojtěchovský & Radek Vejdovský

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Vítek, V., Ryšánek, K., Horáková, Z. et al. Differential behavioural and biochemical effects on the central nervous system by cycloserine isomers. Psychopharmacologia 7, 203–219 (1965). https://doi.org/10.1007/BF00411218

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