title: Efficacy assessment of various anticholinergic agents against topical sarin-induced miosis and visual impairment in rats.
abstract: Eye exposure to the organophosphorus (OP) irreversible acetylcholinesterase inhibitor sarin results in long-term miosis and reduction in visual function. Anticholinergic drugs, such as atropine or homatropine, which are used topically in order to counter these effects may produce mydriasis and partial cycloplegia, which may worsen visual performance. This study was aimed to test the efficacy of short-acting anticholinergic drugs against sarin-induced miosis and visual impairment, which will minimally insult vision. Long-Evans rats, exposed topically to various sarin doses from 0 to 10 μg, showed a dose-dependent miosis, which returned to pre-exposure levels within 24-48 h. Tropicamide treatment rapidly widened the miotic effect to a different extent depending on time following treatment and dosage given. Cyclopentolate, however, showed a delayed response that finally widened the pupils in a dose-dependent manner. Atropine treatment showed a rapid widening of the pinpoint pupils exceeding baseline level finally causing mydriasis. Light reflex test showed that the contraction ability of the iris following atropine treatment was impaired, as opposed to the use of tropicamide which facilitated the iris contraction, similar to control. Finally, tropicamide and atropine treatments ameliorated the visual impairment, as opposed to cyclopentolate, which worsened visual performance. Considering that tropicamide treatment against sarin exposure did not cause mydriasis nor did it impair the iris contraction flexibility as a response to light, the use of this drug should be taken into consideration as a first-choice topical treatment against OP intoxication.
authors.affiliation: Department of Pharmacology, Israel Institute for Biological Research, P.O. Box 19, Ness-Ziona 74100, Israel. arielg@iibr.gov.il
authors.forename: Ariel
authors.initials: A
authors.lastname: Gore
authors.forename: Rachel
authors.initials: R
authors.lastname: Brandeis
authors.forename: Inbal
authors.initials: I
authors.lastname: Egoz
authors.forename: David
authors.initials: D
authors.lastname: Peri
authors.forename: Joseph
authors.initials: J
authors.lastname: Turetz
authors.forename: Eugenia
authors.initials: E
authors.lastname: Bloch-Shilderman
mesh_terms: D000818:Animals; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D008297:Male; D015877:Miosis / Q000139:chemically induced* / Q000503:physiopathology; D051381:Rats; D020318:Rats, Long-Evans; D012524:Sarin / Q000633:toxicity*; D014786:Vision Disorders / Q000139:chemically induced* / Q000503:physiopathology
chemical_list: D002800:Cholinesterase Inhibitors; D012524:Sarin