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.