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Comparative Pharmacology of Analogues of S-nitroso-N-acetyl-DL-penicillamine on Human Platelets

E Salas, M A Moro, S Askew, H F Hodson, A R Butler, M W Radomski, S Moncada

Br J Pharmacol. 1994 Aug;112(4):1071-6.

PMID: 7524991

Abstract:

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 microM), 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 > or = 10 microM. 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.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP67776061 S-Nitroso-N-acetyl-DL-penicillamine S-Nitroso-N-acetyl-DL-penicillamine 67776-06-1 Price
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