Specific Binding of [3H]-1-O-Octadecyl Paf-Acether to Washed Human Platelets

Tuffin, D.P.; Davey, Philip T.; Dyer, R. L.; Lunt, David O.; Wade, P.J.

doi:10.1007/978-1-4615-9442-0_7

Cited by 8 publications

(1 citation statement)

References 9 publications

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“…The effect is also not due to antagonist activity at the Paf-acether receptor. SC 38249 proved inactive in a specific human platelet [3H]-l-0-octadecyl-Paf-acether radioligand binding assay developed in our laboratory (35) at comparable drug concentra tions (data not shown). In addition, notable activity against Pafacether responses was also observed in the dog ex vivo study at both 1 and 3 hours after oral dosing.…”

Section: Discussionmentioning

confidence: 95%

Effect of SC 38249, a Novel Substituted Imidazole, on Platelet Aggregation In Vitro and In Vivo

Lad¹,

Honey²,

Lunt³

et al. 1988

Thromb Haemost

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SummarySC 38249 ((RS)-l-(2,3-bis-[(4-methoxyphenyl)methoxy] propyl)-lH-imidazole) caused dose-related inhibition of collagen- induced thromboxane A2 formation in human platelet rich plasma (IC50: 9.9 ± 1.0 μM) accompanied by a dose-dependent increase in plasma PGE2. Broad inhibitory activity was evident against human platelet aggregatory and secretory responses in vitro.IC50 values of 11.9 ± 1.9 μM (0.64 mM arachidonic acid), 18.3 ± 3.8 μM (0.5 μg ml−-1collagen) and 37.6 ± 6.1 μM (25 nM Paf-acether) were obtained against maximum increase in PRP light transmission achieved by each agonist. Although less potent, SC 38249 retained significant inhibitory activity against PRP responses induced by a higher (3.0 μg ml−-1) concentration of collagen (IC50: 272.5 ± 24.6 μM), and against Paf-acether-induced responses in PRP pre-treated with 10 μM indomethacin (I.C.50: 192.0 ± 16.1 μM).Experimental animal studies confirmed the in vitroanti-aggregatory efficacy of SC 38249, since significant inhibitory activity was observed against Paf-acether and ADP-induced responses in dog PRP ex vivo,anti-Forssman antibody-induced thrombocytopoenia in anaesthetized guinea pigs, and collagen-induced intravascular aggregation in anaesthetized rabbits. Thus, SC 38249 is a novel thromboxane synthase inhibitor which possesses interesting anti-aggregatory properties which cannot wholly be attributed to prevention of platelet thromboxane A2 formation.

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Section: Discussionmentioning

confidence: 95%