A historical perspective and recent advances in prostamide research and therapeutics

In recent years antiglaucoma drugs have been brought to market that were discovered as a result of structure-activity relationship studies of the known ocular hypotensive prostaglandin F2alpha. One such ocular hypotensive agent is bimatoprost, the C1-ethylamide analog of 17-phenyl prostaglandin F2alpha. The in vitro pharmacology of bimatoprost, however, is strikingly different from prostanoid FP-receptor agonists. Another agent, the endocannabinoid anandamide has been demonstrated to be effectively converted by cyclooxygenase COX-2 into prostamide, a new class of fatty acid amide, in which the C1-terminus is an ethanolamide. Prostamides possess their own unique biological activity and have longer half-lives in plasma than prostaglandins, indicating that they may exert actions systemically either as prostaglandin precursors or as unique signal mediators. The independent discoveries of bimatoprost and prostamides from anandamide have potentially opened up a new and intriguing area of research. The purposes of this article are to review the biosynthetic evolution of prostamides, the discovery of bimatoprost and its unique pharmacology along with that of prostamide F2alpha and, finally, data on recently discovered agonists and antagonists.