COMPARATIVE PHARMACOLOGY OF ANALOGS OF S-NITROSO-N-ACETYL-DL-PENICILLAMINE ON HUMAN PLATELETS

1 The effects of two new analogues of S-nitroso-N-acetyI-DL-penicillam ine (SNAP), S-nitroso-N-formyl-DL-penicillamine (SNFP) and S-nitroso-D L-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 co ncentrations. 6 At concentrations sufficient to inhibit platelet funct ion and induce cyclic GMP formation (0.01-3 mu M), the release of NO c ould be detected from SNPL but not from SNAP and SNFP. 7 Release of NO from all compounds was detected at concentrations greater than or equ al to 10 mu M. 8 Thus, the spontaneous release of NO from SNPL explain s the actions of this compound on platelet function; however, platelet -mediated mechanisms may be involved in the release of NO from SNAP an d SNFP.