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OBJECTIVES: To determine if low concentrations of H-7 (1-[5-isoquinoline sulfonyl]-2-methyl piperazine) topically applied to the eye increases outflow facility and decreases intraocular pressure (IOP) without affecting the cornea in monkeys, and to evaluate if the effect of H-7 on IOP is pressure dependent. METHODS: Single or multiple doses of 5% H-7 or vehicle (20 µL) were administered topically to opposite eyes of normal monkeys. A single dose of 2% H-7 or vehicle (50 µL) was administered to the glaucomatous eye of monkeys with laser-induced unilateral glaucoma, with vehicle on day 1 and H-7 on day 2. RESULTS: In normotensive eyes, 1 dose of 5% H-7 maximally decreased IOP by a mean ± SEM of 2.5 ± 1.0 mmHg (-16.7% ± 5.5%) at 3 hours. Higher baseline IOP and repeated dosing were associated with greater IOP reduction. Outflow facility was increased, but central corneal thickness was not affected. In glaucomatous eyes, 1 dose of 2% H-7 maximally decreased IOP by a mean ± SEM of 5.8 ± 0.6 mmHg (-16.9% ± 1.6%) at 2 hours. CONCLUSIONS: Five percent H-7 increases outflow facility and decreases IOP, but does not affect corneal thickness. Multiple doses of H-7 induce greater reduction of IOP than a single dose. The effect of H-7 on IOP may be pressure dependent. CLINICAL RELEVANCE: Multiple topical treatments with low doses of H-7 or analogues may substantially reduce outflow resistance in the hypertensive eye without meaningfully affecting the cornea.
Dr. B. Tian, Ophthalmology and Visual Sciences, University of Wisconsin-Madison Medical School
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)