THE ACTION OF ,5,6,11B-HEXAHYDRO-[1]BENZOTHIENO[3,2-G]INDOLIZINE HYDROCHLORIDE (ADT-16) ON PERIPHERAL AND CENTRAL RESPONSES MEDIATED BY 5-HYDROXYTRYPTAMINERGIC AND ADRENERGIC SYSTEMS OF THE RAT

Some acute pharmacological effects have been examined of racemic ADT 1 6 3,5,6,11b-hexahydro[1]benzothieno[3,2-g]indolizine hydrochloride), o n peripheral and central responses mediated by 5-HT and adrenergic sys tems in the rat. In-vitro, ADT 16 (10-1000 nM), similarly to mianserin , antagonized the inhibitory responses to B-HT 920 of the electrically -stimulated rat isolated prostatic vas deferens. High concentrations o f ADT 16 (10 mu M), also resembled those of mianserin by potentiating twitch responses to electrical stimulation of the tissue. Contractile responses to phenylephrine of rat isolated epididymal vas deferens wer e antagonized by ADT 16 (0.3-1 mu M). In the rat stomach fundus strip, ADT 16 (1-3 mu M) antagonized contractions due to 5-HT. ADT 16 (0.1-1 mu M) had no effect on responses to acetylcholine of the guinea-pig i solated ileum. In-vivo, in spinalized, decerebrated rats, fenfluramine - or clonidine-induced facilitation of flexor reflex activity of the a nterior tibialis muscle was attenuated by ADT 16 (3 and 10 mg kg(-1), i.v., and 3 mg kg(-1), i.v. respectively). In the anaesthetized rat, L -3,4-dihydroxyphenylalanine (L-dopa)- or L-5-hydroxytryptophan (L-5-HT P)-induced increases in the frequency of spontaneous twitches of the a nterior digastricus muscle were attenuated by ADT 16 (1 and 3 mg kg(-1 ), i.v.; n = 4). It is concluded that ADT 16, similarly to mianserin, is a novel peripherally and centrally active antagonist of 5-HT and ad renergic responses in the rat.