Conjunctive effects of the 5HT(2) receptor antagonist, sarpogrelate, on thrombolysis with modified tissue plasminogen activator in different laser-induced thrombosis models

The effect of the serotonin (5HT(2)) receptor antagonist, sarpogrelate, was compared with that of the selective thrombin inhibitor, argatroban, in modified tissue plasminogen activator (mt-PA)-induced thrombolysis using two laser-induced thrombosis models reflecting different levels of vascular endothelial cell damage. Bolus intravenous infusions of mt-PA (0.1, 0.2, 0.4 mg/kg) induced thrombolysis in a dose-dependent manner. Sarpogrelate (4.7 mg/kg b.i. + 1.0 mg/kg/h i.v.) given together with mt-PA (0.2 mg/kg b.i.) optimally enhanced thrombolysis (p < 0.05) in a helium-neon laser-induced model where endothelial damage was minimal but not in an argon laser model where desquamation of endothelial cells was recognized. In contrast, argatroban (0.5 mg/kg b.i. + 0.1 mg/kg/h i.v.) given with mt-PA (0.2 mg/kg b.i.) significantly enhanced thrombolysis in both laser models. The findings indicate that the effectiveness of sarpogrelate in thrombolytic therapy might depend on the extent of vascular damage.