Bito L Z, Baroody R A, Miranda O C
Department of Ophthalmology, College of Physicians and Surgeons, Columbia University, New York, NY 10032.
Exp Eye Res. 1987 Jun;44(6):825-37. doi: 10.1016/s0014-4835(87)80045-3.
The classic primary prostaglandins (PGs), as well as some of their analogs and derivatives, are potent ocular hypotensive agents. The present studies show that A and B PGs, which are derived from PGs of the E type by dehydration and isomerization, have a much greater ocular hypotensive potency than the primary PGs of the E, F or D type. A single application of 5 micrograms of PGA2 to the cat eye in a 25-microliters volume of aqueous vehicle solution yielded a greater and more prolonged ocular hypotensive effect than as much as 100 micrograms of topically applied PGF2 alpha. As little as 1 microgram of PGA2 had a significant ocular hypotensive effect that was enhanced by three or more consecutive daily applications of the same dose. This IOP reduction, which remained significant for several days after the last of 10 daily treatments, was not associated with biomicroscopically detectable flare or invasion of the anterior chamber by cells. Although PGF2 alpha and, to a much lesser extent, PGE2 have a miotic effect in cats, PGs of the A and B type did not cause significant miosis even at doses 50- to 100-fold greater than the minimum dose required to yield significant ocular hypotension. PGA2 retained its ocular hypotensive potency when stored in an aqueous solution at room temperature for four months. The conjunctival hyperemia caused by 5 micrograms or 10 micrograms of A or B type PGs on rabbit eyes was milder and shorter in duration than that caused by the same doses of PGE2 or PGF2 alpha. These findings suggest that derived PGs, especially PGs of the A type, may have a therapeutic advantage over primary PGs for the treatment of ocular hypertension and glaucoma.
经典的初级前列腺素（PGs）及其一些类似物和衍生物是有效的降眼压药物。目前的研究表明，由E型前列腺素通过脱水和异构化衍生而来的A和B型前列腺素，其降眼压效力比E、F或D型初级前列腺素大得多。将5微克PGA2以25微升体积的水性载体溶液单次应用于猫眼，产生的降眼压效果比局部应用多达100微克的PGF2α更大且更持久。低至1微克的PGA2就有显著的降眼压效果，并且通过连续三天或更多天应用相同剂量可增强该效果。在10天每日治疗中的最后一次治疗后，这种眼压降低在数天内仍保持显著，且与生物显微镜下可检测到的房水闪光或细胞侵入前房无关。尽管PGF2α以及在较小程度上PGE2在猫眼中有缩瞳作用，但A和B型前列腺素即使在比产生显著眼压降低所需的最小剂量大50至100倍的剂量下也不会引起显著的缩瞳。当PGA2在室温下于水溶液中储存四个月时，其仍保留降眼压效力。5微克或10微克A或B型前列腺素在兔眼上引起的结膜充血比相同剂量的PGE2或PGF2α引起的结膜充血更轻且持续时间更短。这些发现表明，衍生的前列腺素，尤其是A型前列腺素，在治疗高眼压症和青光眼方面可能比初级前列腺素有治疗优势。
