Department of Ophthalmology, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA.
Curr Eye Res. 2011 Jan;36(1):41-6. doi: 10.3109/02713683.2010.512695.
To evaluate the effect of topical application of avosentan (SPP 301), endothelin receptor type A antagonist, on intraocular pressure (IOP) in monkey eyes with laser-induced unilateral glaucoma.
A multiple-dose study was performed in eight glaucomatous monkey eyes that were topically treated with SPP 301 by applying a 50 µl drop (25 µl × 2) at 9:30 a.m. and 3:30 p.m. for 5 consecutive days at three concentrations (0.003%, 0.03%, or 0.3%). IOP was measured hourly for 6 hrs on each day of the study beginning at 9:30 a.m. for one baseline day, one vehicle-treated day, and treatment days 1, 3, and 5.
Twice daily administration of each of the three concentrations of SPP 301 for 5 days significantly (p < 0.05) reduced IOP. The maximum reduction in IOP occurred 2 or 3 hrs after morning dosing and was 1.8 ± 0.8 (mean ± SEM) mmHg (6%) for 0.003% SPP 301, 4.1 ± 0.7 mmHg (13%) for 0.03% SPP 301, and 7.1 ± 1.3 mmHg (21%) for 0.3% SPP 301. The longest duration of IOP reduction was for 2 hrs with 0.003% SPP 301, and was for at least 6 hrs with 0.03% and 0.3% concentrations. Compared to 0.03% or 0.003% concentrations, 0.3% SPP 301 produced a greater (p < 0.05) IOP reduction. IOP was reduced in fellow untreated normal eyes 2 hr after morning dosing with 0.3% SPP 301, maximum reduction in IOP (11%) occurred on day 1. Of the eyes treated with 0.3% SPP 301, one eye demonstrated mild conjunctival discharge and one eye was closed for 5 min after dosing.
Topically applied SPP 301, an endothelin antagonist, reduced IOP in glaucomatous monkey eyes in a dose-dependent manner. Endothelin antagonists, a novel class of compound, may have potential for the treatment of glaucoma.
评估内皮素受体 A 拮抗剂阿伏生坦（SPP 301）局部应用于激光诱导的单侧青光眼猴眼对眼内压（IOP）的影响。
对 8 只青光眼猴眼进行了多剂量研究，这些猴眼每天上午 9:30 和下午 3:30 通过滴注 50 µl（25 µl×2）接受 SPP 301 治疗，连续 5 天，浓度分别为 0.003%、0.03%或 0.3%。在研究的每一天，从上午 9:30 开始，每小时测量 IOP 6 小时，共进行一天的基线测量、一天的载体处理测量和治疗的第 1、3 和 5 天。
三种浓度的 SPP 301 每天两次给药 5 天，可显著（p<0.05）降低 IOP。IOP 的最大降幅发生在早晨给药后 2 或 3 小时，0.003% SPP 301 组为 1.8±0.8（均值±SEM）mmHg（6%），0.03% SPP 301 组为 4.1±0.7 mmHg（13%），0.3% SPP 301 组为 7.1±1.3 mmHg（21%）。IOP 降低持续时间最长的是 2 小时，用 0.003% SPP 301，用 0.03%和 0.3%浓度至少持续 6 小时。与 0.03%或 0.003%浓度相比，0.3% SPP 301 产生更大的（p<0.05）IOP 降低。在早晨用 0.3% SPP 301 给药后 2 小时，对侧未治疗的正常眼的 IOP 降低，IOP 的最大降幅（11%）发生在第 1 天。用 0.3% SPP 301 治疗的眼睛中，一只眼睛出现轻度结膜分泌物，一只眼睛在给药后 5 分钟内闭合。
局部应用内皮素拮抗剂 SPP 301 以剂量依赖的方式降低了青光眼猴眼的 IOP。内皮素拮抗剂作为一类新型化合物，可能具有治疗青光眼的潜力。
