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Abstract #8498 Published in IGR 5-1
Bimatoprost (Lumigan®) is an agonist at the cloned human ocular FP prostaglandin receptor: real-time FLIPR-based intracellular Ca2+ mobilization studies
Sharif NA; Kelly CR; Williams GWProstaglandins Leukotrienes and Essential Fatty Acids 2003; 68: 27-33
Bimatoprost is the ethyl amide derivative of 17-phenyl-trinor prostaglandin F2ALP. The authors show that bimatoprost (Ki = 9250 ± 846 nM) and bimatoprost free acid (17-phenyl-trinor prostaglandin F2ALP; Ki = 59 ± 6 nM) bind to the FP receptor and displace [3H]-travoprost acid, a selective FP agonist. Bimatoprost (EC50 = 3070 ± 1330 nM), Lumigan® (bimatoprost 0.03% ophthalmic solution; EC50 = 1150 ± 93 nM) and bimatoprost acid (EC50 = 15 ± 3 nM) mobilized intracellular Ca2+ ([Ca2+]i in < five seconds in HEK-293 cells expressing the cloned human ciliary body FP receptor on a fluorometric imaging plate reader (FLIPR). Furthermore, agonist effects of bimatoprost and bimatoprost acid were blocked by AL-8810 (11β-fluoro-15-epi-15-indanyl prostaglandin F2ALP; Ki = 0.7-2.1 μM), an FP receptor-selective antagonist. Therefore, the prodrug bimatoprost and its hydrolytic product, bimatoprost free acid, bind to and activate the human ocular FP prostaglandin receptor to mobilize Ca2+]i, thus behaving as FP receptor agonists.
Dr. N.A. Sharif, Molecular Pharmacology Unit (R2-19), Alcon Research Limited, 6201 South Freeway, Fort Worth, TX 76134, USA. naj.sharif@alconlabs.com
Classification:
11.4 Prostaglandins (Part of: 11 Medical treatment)