Prostaglandin Subtype-Selective and Non-Selective IOP-Lowering Comparison in Monkeys
Prostaglandin Subtype-Selective and Non-Selective IOP-Lowering Comparison in Monkeys
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DOI：
10.1089/jop.2008.0089
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发表时间：
2009-02-01
影响因子：
2.3
通讯作者：
Kaufman, Paul L.
中科院分区：
文献类型：
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作者：
Gabelt, B'Ann True;Hennes, Elizabeth A.;Kaufman, Paul L.
本研究的目的是确定猴子对非选择性前列腺素（PG） f -2a-异丙基酯（ie）的眼内压（IOP）降低反应的程度是否可以通过与其他PG亚型选择性化合物结合来复制。局部使用拉坦前列素（FP激动剂，1.5 μ g，每日1次）、比马前列素（其代谢产物已被证明是FP激动剂，9 μ g，每日1次）、曲伏前列素（FP激动剂，1.2 μ g，每日1次）或EP2激动剂布他前列素（25 μ g，每日1次）4-5天后，眼压降低了约25%。EP1激动剂17-苯基三肽（PhT） PGE2 （b.i.d）和EP3激动剂磺胺酮（b.i.d）没有降低眼压的作用。在拉坦前列素中加入丁前列素、磺胺前列素（10 μ g）或17PhTPGE2 （25 μ g）并不比单独使用拉坦前列素更能降低IOP。然而，拉坦前列素、17PhTPGE2、布他前列素和磺胺前列素联合治疗，IOP降低了50-55%，PGF(2) α -ie （b.i.d）也是如此。综上所述，拉坦前列素、曲伏前列素和比马前列素在血压正常的猴子中产生相似的降低眼压的反应，并且在q.d pm给药时比bi.d给药更有效。本研究中使用的FP、EP1、EP2和EP3激动剂联合使用足以降低与PGF(2) α相同程度的眼压，这表明联合使用pg亚型激动剂可能是一种有效的抗青光眼策略。
The aim of this study was to determine whether the magnitude of the intraocular-pressure (IOP)-lowering response in monkeys to the nonselective prostaglandin (PG) F-2a-isopropyl ester (ie) can be reproduced by combining other PG-subtype-selective compounds. IOP was lowered by approximately 25% after 4-5 days of topical administration with latanoprost (FP agonist, 1.5 mu g, q.d.), bimatoprost (prostamide, whose metabolites have been shown to be FP agonists; 9 mu g, q.d.), or travoprost (FP agonist, 1.2 mu g, q.d) or the EP2 agonist, butaprost (25 mu g, b.i.d.). The EP1 agonist, 17-phenyl trinor (PhT) PGE2 (b.i.d.), and EP3 agonist, sulprostone (b.i.d.), had no IOP-lowering effects. The addition of butaprost, sulprostone (10 mu g), or 17PhTPGE2 (25 mu g) to latanoprost did not lower IOP more than latanoprost alone. However, treatment with the combination of latanoprost, 17PhTPGE2, butaprost, and sulprostone produced a similar 50-55% reduction in IOP, as did PGF(2)alpha-ie (b.i.d.). In conclusion, latanoprost, travoprost, and bimatoprost produce similar IOP-lowering responses in normotensive monkeys and are most efficacious when administered q.d. pm, compared to b.i.d. The combination of the FP, EP1, EP2, and EP3 agonists used in this study was sufficient to lower IOP by the same magnitude as PGF(2)alpha-ie, suggesting that combining PG-subtype agonists may be a potent antiglaucoma strategy.