SELECTIVE ALPHA-2 BLOCKING ACTION OF DG-5128 IN THE DOG MESENTERIC-ARTERY AND RAT VAS-DEFERENS

  • 1 January 1983
    • journal article
    • research article
    • Vol. 227  (1) , 194-198
Abstract
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 > 10-7M 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 inhibitroy effect of guanabenz on the sumpathetic contraction and 3H-release. DG-5128 had no effect on contractile responses to exogenous norepinephrine, epinephrine, dopamine, serotonin, histamine and KCl. Evidently, 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 [competitive antagonistic activity] value for DG-5182 against clonidine was 6.7 .+-. 0.2. The affinity and selectivity of this compound is discussed in comparison to findings with yohimbine.