Antagonistic effects of S9871 or (imidazolinyl-2)-2-dihydro 2,3 benzofurane and its stereoisomers on some central and peripheral actions of alpha 2-agonists.

(+/-) and (+), but not (-) S9871 are new alpha 2-adrenoceptor selective antagonists. The effect of the racemic mixture and of the stereoisomers on cardiovascular and sedative responses to clonidine have been studied in rats and chickens, respectively. Blockade of central alpha 2-adrenoceptors was also measured as a recovery of the sympathoinhibitory effect induced by intravenous administration of B-HT 933 (azepexole). The potency profiles of these agents established in the central nervous system were confirmed in studies using the vas deferens in situ in the pithed rat. (+/-) and (+) S9871 blocked and antagonized some centrally mediated effects of clonidine such as the depressor response to both intravenous and intracerebroventricular administration. However, the return of arterial pressure to the control value, after intravenous administration of (-) S9871, does not result from an antagonistic action on alpha 2-adrenoceptors, since the depressor effects of clonidine were not blocked, but could be explained by alpha-agonistic properties of (-) S9871. (+/-) and (+) S9871 also blocked and antagonized the hypotensive and bradycardic action induced by intravenous administration of B-HT 933. The loss of the righting reflex induced by clonidine in the chicken was prevented by (+/-) and (+) S9871, as shown by a shift of the dose-response curve to clonidine to the right by both agents; on the contrary, (-) S9871 potentiated the sedation induced by clonidine. In the pithed rat, intravenously administered (+/-) and (+) S9871 fully antagonized the inhibitory effects of clonidine on the electrically induced contractions of the vas deferens. These observations are consistent with a selective alpha 2-adrenoceptors antagonistic effect of (+/-) and (+) S9871 at central and peripheral alpha 2-adrenoceptors.