Effect of 5-MCA-NAT, a putative melatonin MT3 receptor agonist, on Intraocular pressure in glaucomatous monkey eyes
Effect of 5-MCA-NAT, a putative melatonin MT3 receptor agonist, on Intraocular pressure in glaucomatous monkey eyes
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DOI：
10.1097/01.ijg.0000133150.44686.0b
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发表时间：
2004-10-01
影响因子：
2
通讯作者：
Yerxa, BR
中科院分区：
文献类型：
--
作者：
Serle, JB;Wang, RF;Yerxa, BR
目的：5-MCA-NAT是一种推测的褪黑激素MT3受体激动剂，可降低眼压正常的家兔眼内眼压。本研究评价局部应用5-MCA-NAT对激光单侧青光眼猴眼眼压的影响。方法：对8只猴子青光眼进行多剂量研究。5- mca - nat 25 μ l滴（2%）于上午9:30和下午3:30局部滴于青光眼，连续5天。用5- mca - nat治疗1、3、5天，从上午9:30开始，每小时测量IOP 6小时。结果：与载药治疗相比，5- mca - nat每日两次，连续5天，第一次给药后1小时至5小时的IOP降低（P < 0.05），并且根据第四次和第八次给药后的IOP测量显示，降低IOP的效果持续至少18小时。5-MCA-NAT的降压作用随着重复给药而增强。IOP最大降低（P < 0.001）发生在每次早晨给药后3小时，第1天为4.0 +/- 0.5（平均+/- SEM） mm Hg(10%)，第3天为5.6 +/- 0.8 mm Hg(15%)，第5天为7.0 +/- 1.1 mm Hg（19%）。在5天的治疗期间，未观察到不良的眼部或全身副作用。结论：5-MCA-NAT是一种推测的褪黑激素MT3受体激动剂，可降低青光眼猴眼的IOP。对MT3受体具有活性的褪黑激素激动剂可能具有治疗眼压升高的临床潜力。
Purpose: 5-MCA-NAT, a putative melatonin MT3 receptor agonist, reduced intraocular pressure (IOP) in ocular normotensive rabbit eyes. This study evaluates the effect of topical application of 5-MCA-NAT on IOP in monkey eyes with laser-induced unilateral glaucoma.Methods: A multiple-dose study was performed in 8 glaucomatous monkey eyes. One 25-muL drop of 5-MCA-NAT (2%) was applied topically to the glaucomatous eye at 9:30 Am and 3:30 Pm for 5 consecutive days. IOP was measured hourly for 6 hours beginning at 9:30 AM for one baseline day, one vehicle-treated day, and treatment days 1, 3, and 5 with 5-MCA-NAT.Results: Compared with vehicle treatment, twice daily administration of 5-MCA-NAT for 5 days reduced (P < 0.05) IOP from 1 hour to 5 hours after the first dose, and the IOP-lowering effects were shown to last at least 18 hours following administration, based on IOP measurements made after the fourth and eighth doses. The ocular hypotensive effect of 5-MCA-NAT was enhanced with repeated dosing. The maximum reduction (P < 0.001) of IOP occurred at 3 hours after each morning dose, and was 4.0 +/- 0.5 (mean +/- SEM) mm Hg (10%) on day 1, 5.6 +/- 0.8 mm Hg (15%) on day 3, and 7.0 +/- 1.1 mm Hg (19%) on day 5. Adverse ocular or systemic side effects were not observed during the 5 days of treatment.Conclusions: 5-MCA-NAT, a putative melatonin MT3 receptor agonist, reduces IOP in glaucomatous monkey eyes. Melatonin agonists with activity on the putative MT3 receptor may have clinical potential for treating elevated IOP.