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Review
. 2008 Feb;153(3):410-9.
doi: 10.1038/sj.bjp.0707434. Epub 2007 Aug 27.

Prostamides (prostaglandin-ethanolamides) and their pharmacology

D F Woodward  1 , Y Liang, A H-P Krauss
Affiliations
Review

Prostamides (prostaglandin-ethanolamides) and their pharmacology

D F Woodward et al. Br J Pharmacol. 2008 Feb.

Abstract

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 F(2alpha) has received the greatest research attention. Prostamide F(2alpha) 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 F(2alpha). 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(2alpha) and bimatoprost but not those of PGF(2alpha) 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 F(2alpha) analogue bimatoprost is the most efficacious ocular hypotensive agent currently available for the treatment of glaucoma.

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Figures

Figure 1
Figure 1
Pharmacology and metabolic conversion of endocannabinoids and neutral prostaglandin derivatives. G, glyceryl ester; PM, prostamide.
Figure 2
Figure 2
Anandamide conversion pathways.
Figure 3
Figure 3
Effect of AGN 204397 (3 × 10−5 M) on contraction of the feline iris produced by (a) prostamide F2α (b) PGF2α (c) bimatoprost (d) and 17-phenyl PGF2α. Open symbols represent vehicle treated preparations, closed symbols represent preparations that received AGN 204397. Values are mean±s.e.m.; n=4.
Figure 4
Figure 4
Structure of prostamide antagonists.
See this image and copyright information in PMC

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