Shih T M
Biochemical Pharmacology Branch, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010-5425.
Brain Res Bull. 1991 Apr;26(4):565-73. doi: 10.1016/0361-9230(91)90097-4.
The effectiveness of diazepam alone or in the presence of atropine sulfate in reversing soman-induced convulsions, inhibition of blood and brain cholinesterase (ChE) activity, and elevation of brain acetylcholine (ACh) and choline (Ch) concentrations in rats was studied. Diazepam (5 mg/kg, IM) blocked the convulsive activity of soman (100 micrograms/kg, SC) whereas atropine sulfate (12 mg/kg, IM) did not. Inclusion of atropine sulfate enhanced the anticonvulsant effects of diazepam. Neither diazepam nor atropine sulfate alone affected ChE activity in the blood and brain of rats, nor did they alone, or in combination, reverse the ChE inhibition induced by soman. Diazepam by itself caused an increase in ACh concentrations in the striatum and a decrease in Ch concentrations in the cortex and striatum. On the other hand, atropine sulfate produced a decrease in ACh and an increase in Ch concentrations in these two brain regions. With combined treatment, diazepam reversed the effect of atropine sulfate on brain ACh and Ch concentrations. Diazepam attenuated the soman-induced elevation of ACh and Ch concentrations in most of the brain regions studied, while atropine sulfate did not. Only when diazepam was given concurrently with atropine sulfate did the elevated brain ACh or Ch concentrations induced by soman return to normal. These results suggest that the anticonvulsant activity of diazepam in soman poisoning may be partially related to its action on presynaptic cholinergic mechanism.
研究了地西泮单独使用或与硫酸阿托品联合使用时，对大鼠沙林诱导的惊厥、血液和脑胆碱酯酶（ChE）活性抑制以及脑乙酰胆碱（ACh）和胆碱（Ch）浓度升高的逆转作用。地西泮（5mg/kg，肌肉注射）可阻断沙林（100μg/kg，皮下注射）的惊厥活性，而硫酸阿托品（12mg/kg，肌肉注射）则不能。加入硫酸阿托品可增强地西泮的抗惊厥作用。地西泮和硫酸阿托品单独使用均不影响大鼠血液和脑中的ChE活性，它们单独使用或联合使用均不能逆转沙林诱导的ChE抑制。地西泮本身可导致纹状体中ACh浓度升高，皮质和纹状体中Ch浓度降低。另一方面，硫酸阿托品可使这两个脑区的ACh浓度降低，Ch浓度升高。联合治疗时，地西泮可逆转硫酸阿托品对脑ACh和Ch浓度的影响。地西泮可减弱沙林诱导的大多数研究脑区中ACh和Ch浓度的升高，而硫酸阿托品则不能。只有当地西泮与硫酸阿托品同时给药时，沙林诱导升高的脑ACh或Ch浓度才会恢复正常。这些结果表明，地西泮在沙林中毒中的抗惊厥活性可能部分与其对突触前胆碱能机制的作用有关。
