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Abstract #20475 Published in IGR 10-1
Prostamides (prostaglandin-ethanolamides) and their pharmacology
Woodward DF; Liang Y; Krauss AH-PBritish Journal of Pharmacology 2008; 153: 410-419
The prostamides are part of a large and continually expanding series of pharmacologically unique neutral lipids. They are COX-2 derived oxidation products of the endocannabinoid/endovanniloid anandamide. Prostamide pharmacology is unique and, as in the case of the endocannabinoids anandamide and 2-arachidonylglycerol, bears little resemblance to that of the corresponding free acids. By virtue of its close relationship to the anti-glaucoma drug bimatoprost, prostamide F2α has received the greatest research attention. Prostamide F2α and bimatoprost effects appear independent of prostanoid FP receptor activation, according to a litany of agonist studies. Studies involving freshly isolated and separate feline iridial smooth muscle cells revealed that bimatoprost and FP receptor agonists stimulated different cells, without exception. This suggests the existence of receptors that preferentially recognize prostamide F2α. The recent discovery of prostamide antagonists has provided further support for prostamide receptors as discrete entities. The prototypical prostamide antagonists, AGN 204396 and 7, blocked the effects of prostamide F 2α and bimatoprost but not those of PGF2α and FP receptor agonists in the feline iris. Second generation more potent prostamide antagonists, such as AGN 211334, should allow the role of prostamides in health and disease to be elucidated. From the therapeutics standpoint, the prostamide F2α analogue bimatoprost is the most efficacious ocular hypotensive agent currently available for the treatment of glaucoma.
Dr. D.F. Woodward, Department of Biological Sciences, Allergan Inc., 2525 Dupont Drive, RD3-2B, Irvine, CA 92612, USA. Woodward_david@allergan.com
Classification:
11.4 Prostaglandins (Part of: 11 Medical treatment)
