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Blockade of central 5-hydroxytryptamine receptors by methiothepin


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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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).

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Key words

  • Brain Serotonin
  • PGO-Spikes
  • Methiothepin
  • Serotonin Antagonist