Comparative pharmacology of analogues of S‐nitroso‐N‐acetyl‐dl‐penicillamine on human platelets

1 The effects of two new analogues of S‐nitroso‐N‐acetyl‐dl‐penicillamine (SNAP), S‐nitroso‐N‐formyl‐dl‐penicillamine (SNFP) and S‐nitroso‐dl‐penicillamine (SNPL), on platelet function were examined in vitro. 2 SNAP and its analogues were potent inhibitors of platelet aggregation and inducers of disaggregation. 3 All compounds inhibited fibrinogen binding to platelets. 4 They also decreased the release of P‐selectin from platelets. 5 Both inhibition of fibrinogen binding and release of P‐selectin correlated with an increase in intraplatelet cyclic GMP concentrations. 6 At concentrations sufficient to inhibit platelet function and induce cyclic GMP formation (0.01–3 μm), the release of NO could be detected from SNPL but not from SNAP and SNFP. 7 Release of NO from all compounds was detected at concentrations ≥ 10 μm. 8 Thus, the spontaneous release of NO from SNPL explains the actions of this compound on platelet function; however, platelet‐mediated mechanisms may be involved in the release of NO from SNAP and SNFP.