The purpose of this study was to compare the efficacy of diazepam and the pro-diazepam avizafone in preventing the severity of soman-induced pathology in guinea pig. Survival, respiration and seizures of experimental animals were investigated with on-line monitoring of respiratory and EEG parameters. Guinea pigs were pretreated with pyridostigmine (0.1mg/kg i.m.) and 30 min later challenged with 1 or 2 LD50 soman. One minute after intoxication they were treated with atropine (3 or 33.8 mg/kg), pralidoxime chloride (32 mg/kg) and either diazepam (2 mg/kg), avizafone (3.5 mg/kg) or saline solution. The highest dose of atropine (33.8 mg/kg) gave a protective effect in groups treated without anticonvulsants by reducing the severity of clinical signs and death within 24 h but also by decreasing seizure occurrence and brain injuries. When injected at the similar molar dose of 7 micromoles/kg, the protection of anticonvulsants against soman neurotoxicity was higher with the atropine/pralidoxime/avizafone combination than with atropine/pralidoxime/diazepam. Indeed, when atropine was used at the lowest dose, avizafone was found to prevent early mortality and seizures occurrence with better efficacy than diazepam. On the other hand, when added to the therapy, the both anticonvulsants did not prevent the moderate EEG depression (reduction of amplitude by 30-52%) observed under 2 LD50 soman. Moreover, the number of animals suffering from respiratory distress (defined as a decrease of minute ventilation of more than 20% from the baseline value) was enhanced when diazepam or avizafone were used in the therapy. This effect was dependent on the atropine dose and the nature of the anticonvulsant. The beneficial effects of the different therapeutics tested were assessed and compared to the previous data obtained with the same therapies against sarin and from the pharmacokinetics properties of the atropine/diazepam mixture.

译文

:本研究的目的是比较地西epa和地西p原阿维扎酮预防豚鼠梭曼病引起的病理严重程度的功效。通过在线监测呼吸和脑电参数来研究实验动物的存活,呼吸和癫痫发作。用吡啶斯的明(0.1mg / kg i.m.)预处理豚鼠,并在30分钟后用1或2个LD50梭曼攻击。中毒后一分钟,他们用阿托品(3或33.8 mg / kg),氯吡肟肟(32 mg / kg)和地西epa(2 mg / kg),阿扎酮(3.5 mg / kg)或盐溶液治疗。在未使用抗惊厥药的组中,最高剂量的阿托品(33.8 mg / kg)通过降低24小时内的临床体征和死亡严重程度,还通过减少癫痫发作和脑损伤,提供了保护作用。当以相似的7摩尔/千克的摩尔剂量注射时,阿托品/普利多肟/阿扎酮组合的抗惊厥药对人神经毒性的保护作用高于阿托品/普利多肟/地西p。的确,当以最低剂量使用阿托品时,发现阿维扎酮比地西epa具有更好的预防早死和癫痫发作的作用。另一方面,当添加到治疗中时,两种抗惊厥药均不能防止在2 LD50梭曼条件下观察到的中度EEG抑郁(幅度降低30-52%)。此外,当在治疗中使用地西epa或阿维沙酮时,遭受呼吸窘迫的动物数量(定义为每分钟通气量比基准值减少超过20%)会增加。该作用取决于阿托品的剂量和抗惊厥药的性质。评估了所测试的不同疗法的有益效果,并将其与使用相同的抗沙林疗法和阿托品/地西p混合物的药代动力学特性得到的先前数据进行了比较。

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