Evaluation of 4-Methylpyrazole as a Potential Therapeutic Dark Adaptation Inhibitor

Abstract

Purpose: To investigate whether 4-methylpyrazole (4-MP; fomepizole; Antizol), an alcohol dehydrogenase inhibitor that delays dark adaptation in laboratory animals, is a possible pharmaceutical agent for the treatment of Stargardt disease. Methods: Healthy adults were given intravenous infusions of either 4-MP or placebo during six weekly visits to assess effects on dark adaptation. Results: Each participant exhibited a linear, rod-and cone-mediated, log-based response during the initial phase of dark adaptation during both placebo and 4-MP sessions. There were no statistically significant differences between the linear slopes of the 4-MP and placebo testing sessions (α = 0.05). Conclusions: 4-MP does not appear to be a sufficient inhibitor of the human visual cycle to be considered further as a clinical treatment for Stargardt disease or similar ocular disorders at this time; however, additional testing of 4-MP inhibition of production of lipofuscin's A2E fluorophore in mouse models of Stargardt disease is still warranted.

KEYWORDS:

• A2E
• dark adaptation inhibition
• lipofuscin
• 4-methylpyrazole
• Stargardt disease