Effects of topical H-7 on outflow facility, intraocular pressure, and corneal thickness in monkeys

Arch Ophthalmol. 2004 Aug;122(8):1171-7. doi: 10.1001/archopht.122.8.1171.

Abstract

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 micro L) were administered topically to opposite eyes of normal monkeys. A single dose of 2% H-7 or vehicle (50 micro L) 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 mm Hg (-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 mm Hg (-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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / administration & dosage*
  • Administration, Topical
  • Animals
  • Aqueous Humor / metabolism*
  • Cornea / drug effects*
  • Disease Models, Animal
  • Enzyme Inhibitors / administration & dosage*
  • Female
  • Glaucoma / drug therapy*
  • Glaucoma / metabolism
  • Intraocular Pressure / drug effects*
  • Laser Coagulation
  • Macaca fascicularis
  • Male
  • Ophthalmic Solutions
  • Trabecular Meshwork / drug effects*
  • Trabecular Meshwork / surgery

Substances

  • Enzyme Inhibitors
  • Ophthalmic Solutions
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine