Hyperglycemic effect of lidamidine in the rat.

Lidamidine, a new antidiarrheal agent, produced a dose-dependent increase in plasma glucose levels in fed rats. The hyperglycemic response was evident 10 min after oral administration of lidamidine and lasted for 4 hr. Lidamidine's effect was absent in alloxanized rats. Insulin administration prevented the hyperglycemia. Pretreatment with the alpha 2-adrenoceptor antagonists yohimbine or RX781094A blocked the hyperglycemic response, while prazosin, propranolol, and hexamethonium pretreatment had no effect. These results indicate that the hyperglycemic effect of lidamidine is primarily due to the activation of peripherally located alpha 2-adrenoceptors that inhibit the release of insulin from pancreatic beta-cells.