Selective alpha-2 blocking action of DG-5128 in the dog mesenteric artery and rat vas deferens.

The effects of a new hypoglycemic agent, DG-5128 (2-[2-(4,5-dihydro-1H-imidazol-2-yl)-1-phenylethyl]pyridine dihydrochloride sesquihydrate), on the adrenergic mechanism were studied in the isolated dog mesenteric artery and rat vas deferens. In the dog mesenteric artery, DG-5128 in concentrations over 10(-7) M augmented the contractile response and [3H]norepinephrine release evoked by electrical stimulation of the sympathetic nerve. Such an enhancement was also observed under conditions of treatment with cocaine and was not inhibited by propranolol or atropine. DG-5128 suppressed the presynaptic alpha-2 adrenoceptor mediated inhibitory effect of guanabenz on the sympathetic contraction and 3H-release. On the other hand, DG-5128 had no effect on the contractile responses to exogenous norepinephrine, epinephrine, dopamine, serotonin, histamine and KCI. These results indicate that DG-5128 is a highly selective alpha-2 antagonist in the mesenteric artery. This conclusion was supported in the experiments with the rat vas deferens; the pA2 value for DG-5128 against clonidine was 6.7 +/- 0.2. The affinity and selectivity of this compound was discussed, in comparison to findings in the case of yohimbine.