Effect of SC 38249, a novel substituted imidazole, on platelet aggregation in vitro and in vivo.

Abstract

SC 38249 [RS)-1-(2,3-bis-[(4-methoxyphenyl)methoxy]propyl)-1H-imidazole) caused dose-related inhibition of collagen-induced thromboxane A2 formation in human platelet rich plasma (IC50: 9.9 +/- 1.0 microM) 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 microM (0.64 mM arachidonic acid), 18.3 +/- 3.8 microM (0.5 microgram ml-1 collagen) and 37.6 +/- 6.1 microM (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 micrograms ml-1) concentration of collagen (IC50: 272.5 +/- 24.6 microM), and against Paf-acether-induced responses in PRP pre-treated with 10 microM indomethacin (I.C.50: 192.0 +/- 16.1 microM). Experimental animal studies confirmed the in vitro anti-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 thrombocytopenia 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.

• Authors: N Lad, A C Honey, D O Lunt, R F Booth, J Westwick, P W Manley, D P Tuffin
• Journal: Thrombosis and haemostasis (Thromb Haemost) Vol. 59 Issue 2 Pg. 164-70 (Apr 08 1988) ISSN: 0340-6245 [Print] Germany
• PMID: 3133807 (Publication Type: Journal Article)

Chemical References

• Arachidonic Acids
• Imidazoles
• Prostaglandins E
• Arachidonic Acid
• Thromboxane A2
• 1-(2,3-bis((4-methoxyphenyl)methoxy)propyl)-1H-imidazole
• Collagen
• Thromboxane-A Synthase
• Dinoprostone

Topics

• Adolescent
• Adult
• Animals
• Arachidonic Acid
• Arachidonic Acids (pharmacology)
• Collagen (pharmacology)
• Dinoprostone
• Dogs
• Humans
• Imidazoles (pharmacology)
• In Vitro Techniques
• Male
• Platelet Aggregation (drug effects)
• Prostaglandins E (blood)
• Rabbits
• Thrombocytopenia (prevention & control)
• Thromboxane A2 (blood)
• Thromboxane-A Synthase (antagonists & inhibitors)