CICLAZINDOL INHIBITS ATP-SENSITIVE K-SECRETION IN CRI-G1 INSULIN-SECRETING CELLS( CHANNELS AND STIMULATES INSULIN)

Ciclazindol, an anorectic drug, was shown to inhibit ATP-sensitive K(K-ATP) channel currents and stimulate insulin secretion from CRI-G1 i nsulin-secreting cells. In contrast, the structurally related anorecti c agent mazindol and the amphetamine-based anorectic compounds diethyl propion, fenfluramine, and phentermine had no effect on K-ATP channel activity in this cell line. Similarly, ciclazindol elicited insulin se cretion from CRI-G1 cells, whereas mazindol had no secretagogue action . The mechanism by which ciclazindol acts to inhibit K-ATP channel act ivity is different than that of the sulfonylureas as ciclazindol is ef fective after procedures that decouple the sulfonylurea receptor from the K-ATP channel. In agreement with this finding, ciclazindol failed to displace [H-3]glibenclamide from CRI-G1 microsomal membranes. Furth er experiments demonstrated that ciclazindol has no significant effect on voltage-activated currents in this cell line.