Blockade of central 5-hydroxytryptamine receptors by methiothepin

Abstract

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. © 1972 Springer-Verlag.