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J. B. Serle, R.-F. Wang, B. Levy, B. Katz; Effects of DNB-001 - A Novel Ion Channel Modulator - On Intraocular Pressure in Glaucomatous Monkey Eyes. Invest. Ophthalmol. Vis. Sci. 2009;50(13):1474.
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© ARVO (1962-2015); The Authors (2016-present)
Oral DNB-001, a novel ion channel modulator, has been shown to have dual actions of neuroprotection and decreasing IOP in rodent models of glaucoma. This study investigated the effect of topical DNB-001 on intraocular pressure (IOP) in monkey eyes with laser-induced glaucoma.
A multiple-dose study was performed in glaucomatous monkey eyes, 8 eyes received concentrations of 3% or 10%. IOP was measured hourly for 6 hrs on each study day. Following one baseline day (untreated) and one vehicle-treated day, 25µl x 2 drops of DNB-001, 3% or 10%, were applied topically to glaucomatous eyes BID for 5 consecutive days.
3% DNB-001 reduced IOP (p<0.05) at 2 hrs and 4 hrs after AM dosing on day 3, and at 2 hrs and 3 hrs after AM dosing on day 5. Maximum reduction in IOP was 4.1 ± 0.8 (mean ± SEM) mmHg (14%) 2 hrs after AM dosing on day 5. 10% DNB-001 reduced (p<0.05) IOP beginning 1 hr after the AM dose on day 3 and IOP remained decreased through 6 hrs post-dosing. Maximum IOP reduction on day 3 was 4.4 ± 0.5 mmHg (15%) at 2 hrs after AM dosing. On treatment day 5, a reduction (p<0.05) in IOP was observed from 0 hr to 6 hrs with the maximum reduction in IOP of 5.6 ± 1.0 mmHg (19%) at 2 hrs post-dosing. The longest duration of IOP reduction was at least 18 hrs after the PM dosing on day 4. Enhancement of IOP reduction was observed after repeated dosing with 10% concentration. Compared with the 3% concentration, 10% DNB-001 had a longer duration of action (18 vs. 2 hrs) and caused a greater (p<0.05) reduction in IOP. Ocular side effects were not observed.
Topically applied DNB-001 reduced IOP in glaucomatous monkey eyes in a dose-dependent manner. Given its potential neuroprotective effects, its ion channel modulation and its unique physical-chemical properties that may lend themselves to sustained drug delivery, DNB-001 offers potential for the treatment of glaucoma.
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