¹Department of Biological Sciences, Allergan Inc., Irvine, CA, USA

Correspondence: Dr DF Woodward, Department of Biological Sciences, Allergan Inc., 2525 Dupont Drive, RD3-2B, Irvine, CA 92612, USA. E-mail: woodward_david@allergan.com

²Current address: Pfizer Inc., San Diego, CA, USA.

Received 2 May 2007; Revised 9 July 2007; Accepted 26 July 2007; Published online 27 August 2007.

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 F₂ has received the greatest research attention. Prostamide F₂ 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 F₂. 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 F₂ and bimatoprost but not those of PGF₂ 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 F₂ analogue bimatoprost is the most efficacious ocular hypotensive agent currently available for the treatment of glaucoma.