Antagonism of obidoxime on sarin induced miosis and visual impairment in rabbits / 中国药理学与毒理学杂志

ABSTRACT

OBJECTIVE The antagonism of obidoxi me on sarin induced miosis and visual impair-ment was evaluated and its antagonistic mechanism was investigated.METHODS ① 30 min after sarin (2 μg /0.1 mL per eye)was given as an eyedrop,the ability of the 2.5%,5.0%,7.5% obidoxi me and 1 .0% atropine to reverse effects of sarin on pupil dia meter and light reflex were evaluated at different ti mes.② Another 36 rabbits received sarin and at 30 min afer sarin exposure,the drugs above were ad-ministrated and their effects on pupillary light reflex,as well as the AChE activity of cornea,iris and reti-na were recorded 4h after the treatment.RESULTS ① Miosis and impaired pupillary light reflex oc-curred soon after sarin exposure but the abnormal pupil width and pupillary light reflex had disappeared by 48 h after sarin exposure;Subcequent to 1 .0% atropine treatment,the pupil dilatedinstead while the impaired light reflex did not i mprove significantly;unlike atropine,soon after ad ministration of 2.5%, 5.0%,7.5% obidoxi me,the pupil dia meter and light reflex were significantly increased(P <0.01 )and then had beco me normal totally by 24 h post-dose,much faster than those of the control and atropine treatment group.However,there was no significant difference in the recovery ti me between the different dose groups of obidoxi me.② 4h after treatment,the AChE activity in cornea and irisof sarin-treated group were (42 ±4)%,(26 ±2)%,respectively;the AChE activity in cornea of 2.5%,5.0%,7.5%obidoxi me were (74 ±1 1 )%,(81 ±10)% and (74 ±7)%,respectively,and the AChE activity in iris were(39 ±10)%,(43 ±8)% and (43 ±8)%,respectively ,co mpared with sarin-treated group,AChE activities of cornea and iris as well as light reflex of the obidoxi me-treated group were significantly increased(P<0.01 ).But there was no difference in light reflex and AChE activity between the sarin-treated and atropine-treated groups.CONCLUSION Obidoxi me showed better antagonism of sarin-induced ocular effects than that of the commonly used drug,atropine;the antagonistic mechanism is likely closely related to its rapid reactivation of the inhibited AChE in the cornea and iris.