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Blockade of central 5-hydroxytryptamine receptors by methiothepin

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Summary

Methiothepin (1-[10,11-dihydro-8-(methylthio)dibenzo[b,f] thiepin-10-yl]-4-methylpiperazine maleate), a representative of a new class of neuroleptics, is shown to be an antagonist of 5-hydroxytryptamine (5-HT) at receptors in the CNS. The neuropharmacological evidence was obtained by observing its effects on ponto-geniculo-occipital (PGO) spikes induced in curarized cats by either the benzoquinolizine Ro 4-1284 or p-chlorophenylalanine. Methiothepin a) increased the number of drug-induced spikes, b) antagonized the inhibitory action of 5-HTP and LSD on the spikas, and c) induced PGO-spikes by itself in untreated animals. The turnover of 5-HT in the rat brain was accelerated by methiothepin as indicated by virtually unaltered 5-HT levels, an increase of 5-hydroxyindole acetic acid, an enhancement of the 5-HT increase induced by a MAO inhibitor and by an increase of tryptophan levels in the brain.

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Authors and Affiliations

  1. Abteilung für Experimentalle Medizin, F. Hoffmann-La Roche & Co., Basel

    M. A. Monachon, W. P. Burkard, M. Jalfre & W. Haefely

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  1. M. A. Monachon
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  2. W. P. Burkard
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  3. M. Jalfre
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  4. W. Haefely
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Monachon, M.A., Burkard, W.P., Jalfre, M. et al. Blockade of central 5-hydroxytryptamine receptors by methiothepin. Naunyn-Schmiedeberg's Arch. Pharmacol. 274, 192–197 (1972). https://doi.org/10.1007/BF00501854

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  • DOI: https://doi.org/10.1007/BF00501854

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