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Evaluation of 4-methylpyrazole as a potential therapeutic dark adaptation inhibitor
Cory Jurgensmeier1, Prakash Bhosale, Paul S Bernstein
1Moran Eye Center, University of Utah, Salt Lake City, Utah 84132, USA.
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 (alpha = 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.
