Burk Robert M, Woodward David F
Allergan Inc, Gavin Herbert Research Building, 2525 Dupont Drive, Irvine, CA 92612, USA.
Curr Opin Drug Discov Devel. 2007 Jul;10(4):413-21.
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.
近年来，通过对已知的降眼压前列腺素F2α进行构效关系研究，已将抗青光眼药物推向市场。其中一种降眼压药物是比马前列素，它是17-苯基前列腺素F2α的C1-乙基酰胺类似物。然而，比马前列素的体外药理学与前列腺素FP受体激动剂显著不同。另一种药物，内源性大麻素花生四烯酸乙醇胺已被证明可被环氧化酶COX-2有效地转化为前列腺酰胺，这是一类新的脂肪酸酰胺，其中C1-末端是乙醇酰胺。前列腺酰胺具有其自身独特的生物活性，并且在血浆中的半衰期比前列腺素更长，这表明它们可能作为前列腺素前体或作为独特的信号介质在全身发挥作用。从花生四烯酸乙醇胺中独立发现比马前列素和前列腺酰胺，可能开辟了一个新的有趣的研究领域。本文的目的是综述前列腺酰胺的生物合成演变、比马前列素的发现及其独特的药理学以及前列腺酰胺F2α的药理学，最后综述最近发现的激动剂和拮抗剂的数据。
