Ionophoretic activity of hypoglycemic sulfonylureas.

Hypoglycemic sulfonylureas, such as tolbutamide, gliclazide and glipizide, provoked the translocation of Ca from an aqueous medium into or across an organic immiscible phase. The amount of Ca translocated into the organic phase was proportional to the square of the drug concentration, and appeared saturable at high Ca concentration. Non-hypoglycemic sulfonylureas and diazoxide had little or no effect upon Ca translocation. The ionophoretic capacity of the hypoglycemic sulfonylureas was antagonized by suloctidil. Tolbutamide and gliclazide also provoked Na translocation into the organic phase, the amount of Na translocated being proportional to the drug concentration. Gliclazide-mediated Ca translocation was inhibited in a dose-related fashion by increasing concentrations of Na+ or H+. It is proposed that the ionophoretic capacity of hypoglycemic sulfonylureas may participate in their insulinotropic action.