Pharmacology of B-HT 920 in some isolated smooth muscles of the guinea-pig.

The effects of B-HT 920 were investigated on four isolated preparations from the guinea-pig, namely the aorta, trachea, ileum and vas deferens. The latter three preparations were studed during electrical field stimulation, which induced contractions by activating cholinergic neurones (trachea and ileum) or adrenergic neurones (vas deferens), respectively. Comparative studies were also made with clonidine and noradrenaline. In ileum and trachea B-HT 920 was almost equipotent with noradrenaline to inhibit the electrically induced contractions. In these tissues, B-HT 920 also displayed almost the same maximal effect as noradrenaline. Clonidine also inhibited the contractions in ileum and trachea; the drug was slightly more potent than noradrenaline. However, in contrast to the intrinsic activity of B-HT 920 that of clonidine was only submaximal. In vas deferens both B-HT 920 and clonidine induced inhibition of contractions on electrical field stimulation at low concentrations. In this organ, both drugs were capable of inducing complete inhibition of the contractile response. In aorta B-HT 920 as well as clonidine were only weak agonists in comparison to noradrenaline. The alpha2-blocker, yohimbine, completely blocked the effect of B-HT 920 in ileum at low concentrations (1 x 10(-7) M). Remarkably, however, the inhibitory action of B-HT 920 in trachea was only marginally affected even by high concentrations of yohimbine (1 x 10(-6) M). It is suggested from the present results that B-HT 920 can induce inhibition of both cholinergic and adrenergic neurotransmission presumably by inducing selective stimulation of prejunctional alpha2-receptors. In fact, the selectivity of B-HT 920 seems to be comparable to that of clonidine for the alpha2-receptor. However, the mode of action of B-HT 920 in trachea may be somewhat uncertain since its effect was not inhibited by yohimbine.