EFAROXAN ACTS PERIPHERALLY TO BLOCK THE ANTISECRETORY AND GASTROPROTECTIVE EFFECTS OF MOXONIDINE IN RATS

I-1-imidazoline receptor activation by moxonidine has potent antigastr ic secretory and gastroprotective effects in Fats. We therefore tested whether an imidazoline receptor antagonist, efaroxan, would influence gastric secretion and block the antisecretory and antiulcer effects o f moxonidine. When given intracerebroventricularly (i.c.v.), moxonidin e inhibited basal acid output in conscious rats to a maximum of 38%. M oxonidine given i.p. also significantly increased gastric adherent muc us levels in rats subjected to cold-restraint stress. Efaroxan alone g iven i.c.v., did not influence gastric secretion nor did it affect mox onidine's ability to decrease gastric secretion. Similarly, peripheral ly administered efaroxan did not block the antisecretory effect of mox onidine given i.c.v. However, when both compounds were given i.p., efa roxan pretreatment at ail but the lowest doses significantly blocked t he antigastric secretory effect of moxonidine. Efaroxan alone (i.p.) d id not influence stress-induced gastric mucosal injury or adherent muc us levels. However, pretreatment of rats with efaroxan i.p. significan tly blocked the mucus-preserving effect of i.p. moxonidine. These resu lts demonstrate that central (i.c.v.) or peripheral (i.p.) administrat ion of the I-1-imidazoline receptor agonist moxonidine is associated w ith gastroprotection. The ability of i.p. efaroxan to block the effect s of i.p. moxonidine but not i.c.v. moxonidine indicates that imidazol ine receptors located centrally and peripherally may represent two uni que sites associated with gastroprotection.