THROMBOSIS RESEARCH Printed in the United States Vol. 6, PP- zyxwvutsrqponmlkjihgfedcb 345-355, 1975 Pergamon Press, Inc. EFFECTS OF GLICLAZIDE, A NEW ANTIDIABETIC AGENT, ON THE PLATELET RELEASE REACTION, ROLE OF ADENYLATE CYCLASE. Michel LAGARDE+, Marc DECHAVANNE+, Jean-Paul THOUVEREZ+, and Monique VERRY* t Haematology Laboratory, Institut Pasteur, 69007-Lyon and _+t Clinical Research Department, Servier Laboratories, 22 rue Garnier, 92200-Neuilly/Seine FRANCE (Received 16.5.1974; in revised form 23.17.1974. Accepted by Editor S. Niewiarowski. Received by Executive Editorial Office 21.1.1975.) ABSTRACT Gliclazide, a sulphonylurea derivative possessing an "in viva" hypoglycaemic action, inhibits "in vitro" pl telet release induced It does not alter I$02 production from ucose, but opposes its increase by thrombin. I is an activator of adenylate cyclase increasing th level of [ # AMP formed within the intact platelets from 3H adenine or t1 5 yclic $1 H adenosine. Finally, it inhibits the effects of thrombin and collagen on platelet adenylate cyclase activity. INTRODUCTION Previous pharmacological studies have demonstrated, at the level of the microcirculation, the anti-thrombotic action of gliclazide, a synthesized derivative of sulphonylu;ea or (methyl-4 phenyl C sulphonyl) - 1 (perhydrocy- clopenta (2) pyrrolyl-2)J - 3 urea : the administration of gliclazide to the rat prior to an electrically induced lesion of the arteriolar endothelium in the mesocaecum delays the appearance of a mural platelet thrombus, lessens the tendency of the thrombus to develop toward complete obliteration, shortens its duration and accelerates the speed of its disappearance (1). In the same way, in the dog, gliclazide prevents retinal capillary occlusion following perfusion with A.D.P. (2) and in man, it inhibits platelet adhesion and aggregation (3,4). We by therefore studied the effects of gliclazide on the release reaction induced thrombin and by collagen. 345