Effects of oral hypoglycaemic agents on platelet functions.
The in vitro effects of three oral hypoglycaemic agents, gliclazide (1-(4-methylbenzensulfonyl)-3-[3-azabicylo(3,3,0)octyl]urea) , glibenclamide (1-[4-[2-(chloro-2-methoxybenzamide)-ethyl]-phenyl- sulfonyl]-3-cyclohexyl-urea) and glimepiride (1-[4-[2-(3-ethyl-4-methyl-2-oxo-3-pyrroline-carboxamide)- ethyl]-phenylsulphonyl]3-(4-methylcyclohexyl)-urea), on functions of human platelets were evaluated. None of these agents up to a concentration of 40 microM inhibited platelet aggregation induced by thrombin. Glibenclamide and glimepiride in the range of 20-40 microM suppressed Ca2+ release from internal Ca2+ stores induced by thrombin. Gliclazide showed no effect on arachidonic acid metabolism of human platelets. Glimepiride selectively inhibited the cyclooxygenase pathway, while the activities of 12-lipoxygenase and phospholipase A2 were unaffected. Glibenclamide inhibited both the cyclooxygenase and 12-lipoxygenase pathways. It also attenuated arachidonic acid release from phospholipase A2. Oral hypoglycaemic agents with inhibitory effects on arachidonic acid metabolism may prove useful for the treatment of diabetic patients with enhanced platelet functions.
Ozaki
Y
Y
Department of Clinical and Laboratory Medicine, Yamanashi Medical College, Japan.
Yatomi
Y
Y
Kume
S
S
D016718:Arachidonic Acid / Q000378:metabolism / Q000494:pharmacology; D002118:Calcium / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D016257:Fura-2; D005907:Gliclazide / Q000494:pharmacology*; D005905:Glyburide / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D015539:Platelet Activation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013453:Sulfonylurea Compounds / Q000008:administration & dosage / Q000494:pharmacology*
D010975:Platelet Aggregation Inhibitors; D013453:Sulfonylurea Compounds; D016718:Arachidonic Acid; D015759:Ionomycin; C057619:glimepiride; D005907:Gliclazide; D005905:Glyburide; D002118:Calcium; D016257:Fura-2