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首页> 外文期刊>Toxicological sciences: An official journal of the Society of Toxicology >Anticholinergic and antiglutamatergic agents protect against soman-induced brain damage and cognitive dysfunction.
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Anticholinergic and antiglutamatergic agents protect against soman-induced brain damage and cognitive dysfunction.

机译：抗胆碱能药和抗谷氨酰胺能药可防止梭曼引起的脑损伤和认知功能障碍。

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Soman, a powerful inhibitor of acetylcholinesterase, causes an array of toxic effects in the central nervous system including convulsions, learning and memory impairments, and, ultimately, death. We report on the protection afforded by postexposure antidotal treatments, combined with pyridostigmine (0.1 mg/kg) pretreatment, against these consequences associated with soman poisoning. Scopolamine (0.1 mg/kg) or caramiphen (10 mg/kg) were administered 5 min after soman (1.2 LD50), whereas TAB (i.e., TMB4, atropine, and benactyzine, 7.5, 3, and 1 mg/kg, respectively) was injected in rats concomitant with the development of toxic signs. Atropine (4 mg/kg) was given to the two former groups at the onset of toxic symptoms. Caramiphen and TAB completely abolished electrographic seizure activity while scopolamine treatment exhibited only partial protection. Additionally, no significant alteration in the density of peripheral benzodiazepine receptors was noted following caramiphen or TAB administration, while scopolamine application resulted in a complex outcome: a portion of the animals demonstrated no change in the number of these sites whereas the others exhibited markedly higher densities. Cognitive functions (i.e., learning and memory processes) evaluated using the Morris water maze improved considerably by the three treatments when compared to soman-injected animals; the following rank order was observed: caramiphen > TAB > scopolamine. Additionally, statistically significant correlations (r = 0.72, r = 0.73) were demonstrated between two learning parameters and [3H]Ro5-4864 binding to brain membrane. These results show that drugs with a pharmacological profile consisting of anticholinergic and antiglutamatergic properties such as caramiphen and TAB, have a substantial potential as postexposure therapies against intoxication by organophosphates.
机译：Soman，一种强大的乙酰胆碱酯酶抑制剂，在中枢神经系统中引起一系列毒性作用，包括抽搐，学习和记忆障碍，甚至最终导致死亡。我们报告了暴露后解毒治疗与吡啶斯的明（0.1 mg / kg）预处理相结合所提供的保护作用，以防止与梭曼中毒相关的这些后果。梭曼（1.2 LD50）后5分钟给予东pol碱（0.1 mg / kg）或卡拉咪芬（10 mg / kg），而TAB（即TMB4，阿托品和苯内替嗪分别为7.5、3和1 mg / kg）给药将其注射到伴随中毒迹象发展的大鼠中。在出现中毒症状时，将前两组给予阿托品（4 mg / kg）。 Caramiphen和TAB完全消除了电子癫痫发作的活动，而东pol碱治疗仅表现出部分保护作用。此外，在服用卡咪芬或TAB后，未发现外周苯二氮卓类受体的密度发生显着变化，而东pol碱的施用导致复杂的结果：一部分动物的这些部位数量没有变化，而其他动物的密度明显更高。 。与注射梭曼的动物相比，通过三种处理，使用莫里斯水迷宫评估的认知功能（即学习和记忆过程）显着提高;观察到以下等级顺序：卡拉米芬> TAB>东pol碱。另外，在两个学习参数和[3H] Ro5-4864与脑膜的结合之间证明了统计学上显着的相关性（r = 0.72，r = 0.73）。这些结果表明，具有抗胆碱能和抗谷氨酰胺能性质的药理学特征的药物，例如卡马芬和TAB，具有很大的潜力，可作为防止有机磷酸盐中毒的暴露后疗法。

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