The Hyperglycemic and Antidiuretic Activity of a Phthalimidine Analogue: 1-Oxo-3-(4′-chlorophenyl)-3-hydroxyisoindoline (C3/76) ∗

Abstract

Summary

An analogue of chlorthalidone (C3/76) has been studied in an attempt to obtain a long acting hyperglycemic agent. In rats C3/76 (administered i.p.) caused a dose-related hyperglycemia which lasted longer than that of diazoxide and was reversed by insulin. The drug was effective in both fed and fasted animals and the hyperglycemia was accompanied by a reduced urine output. In the dog, i.v. administration of C3/76 caused hyperglycemia, a fall in blood pressure, an inhibition of insulin secretion, a rise in serum free fatty acid levels, and no significant change in serum catecholamine levels. In in vitro studies with isolated rabbit pancreas, C3/76 reduced insulin secretion, while chlorthalidone had no effect. It can therefore be concluded, that C3/76 produces hyperglycemia by inhibition of insulin secretion similar to one of the reported modes of action of diazoxide. It has similar side effects, hypotension and antidiuresis, even though its chemical structure is quite dissimilar to that of diazoxide.