title: Efficacy assessment of a combined anticholinergic and oxime treatment against topical sarin-induced miosis and visual impairment in rats.
abstract: OBJECTIVE
  Eye exposure to the organophosphorus (OP) irreversible cholinesterase inhibitor sarin results in long-term miosis and impaired visual function. We have previously shown that tropicamide is better at ameliorating this insult than topical atropine or cyclopentolate. However, to minimize side effects associated with repeated tropicamide applications and high treatment doses, we evaluated the effects of oximes (ChE re-activators) alone and combined with tropicamide at ameliorating OP-induced ocular impairments.
  
  
  METHODS
  Rats were topically exposed to sarin, followed by topical treatment with various oximes alone or in combination with tropicamide. Pupil width and light reflex were measured by an infrared-based digital photograph system, while visual performance was assessed by employing the cueing version of the Morris water maze (MWM).
  
  
  RESULTS
  Oxime treatment following sarin ocular exposure induced a slow persistent pupil widening with efficacy in the order of HLö-7 > HI-6 > obidoxime = TMB-4 = MMB-4. In the light reflex test, the ability of the iris to contract following oxime treatment was mostly impaired at 1 h and was back to normal at 4 h following sarin exposure. All oxime treatments ameliorated the sarin-induced visual impairment as tested in the visual task (MWM). The combined topical treatment of tropicamide with an oxime induced a rapid improvement in pupil widening, light reflex and visual performance, and enabled a reduction in tropicamide dose.
  
  
  CONCLUSIONS
  The use of tropicamide combined with an oxime should be considered as the topical treatment of choice against the toxic effects of ocular OP exposure.
authors.affiliation: Department of Pharmacology, Israel Institute for Biological Research, Ness-Ziona, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Gore
authors.forename: E
authors.initials: E
authors.lastname: Bloch-Shilderman
authors.forename: I
authors.initials: I
authors.lastname: Egoz
authors.forename: J
authors.initials: J
authors.lastname: Turetz
authors.forename: R
authors.initials: R
authors.lastname: Brandeis
mesh_terms: D000287:Administration, Topical; D000818:Animals; D018680:Cholinergic Antagonists / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D008297:Male; D015877:Miosis / Q000139:chemically induced / Q000188:drug therapy*; D010091:Oximes / Q000008:administration & dosage*; D051381:Rats; D020318:Rats, Long-Evans; D012524:Sarin / Q000633:toxicity*; D016896:Treatment Outcome; D014331:Tropicamide / Q000008:administration & dosage*; D014786:Vision Disorders / Q000139:chemically induced / Q000188:drug therapy*
chemical_list: D018680:Cholinergic Antagonists; D010091:Oximes; D012524:Sarin; D014331:Tropicamide
keywords: HI-6; HLö-7; Long-Evans rats; MMB-4; TMB-4; anticholinergic treatments; cued MWM; miosis; obidoxime; organophosphates; oxim; pupillary light reflex; sarin; tropicamide; visual impairment