title: Evaluation of 4-methylpyrazole as a potential therapeutic dark adaptation inhibitor.
abstract: OBJECTIVE
  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.
authors.affiliation: Moran Eye Center, University of Utah, Salt Lake City, Utah 84132, USA.
authors.forename: Cory
authors.initials: C
authors.lastname: Jurgensmeier
authors.forename: Prakash
authors.initials: P
authors.lastname: Bhosale
authors.forename: Paul S
authors.initials: PS
authors.lastname: Bernstein
mesh_terms: D003623:Dark Adaptation / Q000187:drug effects* / Q000502:physiology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D000077604:Fomepizole; D005808:Genes, Recessive; D006801:Humans; D007275:Injections, Intravenous; D008266:Macula Lutea; D008297:Male; D011720:Pyrazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D017949:Retinal Cone Photoreceptor Cells / Q000187:drug effects / Q000502:physiology; D012164:Retinal Diseases / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D017948:Retinal Rod Photoreceptor Cells / Q000187:drug effects / Q000502:physiology; D017211:Treatment Failure
chemical_list: D011720:Pyrazoles; D000077604:Fomepizole