Department of Pharmacology, Israel Institute for Biological Research, P.O. Box 19, Ness-Ziona 74100, Israel.
Toxicol Sci. 2012 Apr;126(2):515-24. doi: 10.1093/toxsci/kfs009. Epub 2012 Jan 12.
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.
眼睛暴露于有机磷(OP)不可逆乙酰胆碱酯酶抑制剂沙林会导致长期的瞳孔缩小和视觉功能下降。拟胆碱能药物,如阿托品或氢溴酸东莨菪碱,被局部用于对抗这些作用,可能会导致瞳孔散大和部分睫状肌麻痹,从而可能会恶化视觉表现。本研究旨在测试短效拟胆碱能药物对抗沙林引起的瞳孔缩小和视觉损伤的疗效,因为这种方法对视力的损伤最小。暴露于不同剂量(0 至 10 μg)沙林的长耳大仓鼠,表现出剂量依赖性的瞳孔缩小,在 24-48 小时内恢复到暴露前水平。托吡卡胺治疗根据治疗后时间和剂量的不同,迅速扩大瞳孔缩小的作用程度。然而,环戊醇显示出延迟的反应,最终以剂量依赖的方式扩大瞳孔。阿托品治疗迅速扩大针尖样瞳孔,超过基线水平,最终导致瞳孔散大。光反射试验表明,与使用托吡卡胺促进虹膜收缩相反,阿托品治疗后虹膜的收缩能力受损,与对照组相似。最后,托吡卡胺和阿托品治疗改善了视觉损伤,而环戊醇则恶化了视觉表现。考虑到托吡卡胺治疗沙林暴露不会导致瞳孔散大,也不会损害虹膜对光的收缩灵活性,因此应该考虑将这种药物作为对抗 OP 中毒的首选局部治疗药物。