Imidazenil: a potent and safe protective agent against diisopropyl fluorophosphate toxicity
Imidazenil: a potent and safe protective agent against diisopropyl fluorophosphate toxicity
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DOI：
10.1016/j.neuropharm.2003.09.010
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发表时间：
2004-03-01
影响因子：
4.7
通讯作者：
Guidotti, A
中科院分区：
文献类型：
--
作者：
Auta, J;Costa, E;Guidotti, A
抽搐是有机磷（OP）神经毒剂引起的神经毒性的主要和危及生命的迹象。因此，早期使用抗惊厥药物进行干预，以控制癫痫发作的传播以及由此产生的OP暴露期间可能发生的不可逆转的神经元损伤是至关重要的。安定是OP中毒治疗中常用的标准抗惊厥药。然而，它的使用与一些不良影响有关，包括镇静、健忘症，以及在大剂量使用这种治疗时，呼吸抑制。此外，长期服用地西泮与耐受性和依赖性有关。在这项研究中，我们比较了地西泮（GABA作用的完全变构调节剂）和咪唑米（GABA作用的部分、选择性变构调节剂）作为预防氟磷酸二异丙基（DFP）引起的惊厥和死亡的疗效和安全性。我们的结果表明咪唑尼在保护大鼠免受dfp引起的惊厥和死亡方面比地西泮更有效。此外，咪唑尼在剂量（1和0.5 mg/kg）下是有效的，我们之前已经证明它没有镇静、健忘症、呼吸抑制、耐受性和/或依赖性。相反，地西泮在剂量（5和2.5 mg/kg）产生镇静、健忘症和共济失调时有效。此外，咪唑尼与阿托品合用比与地西泮合用更有效。(C) 2003 Elsevier Ltd.版权所有。
Convulsions are major and life-threatening signs of organophosphate (OP) nerve agents induced neurotoxicity. Thus, early intervention with anticonvulsant drugs to control seizure propagation and the consequent irreversible neuronal damage that may occur during OP exposure is essential. Diazepam is the standard anticonvulsant used in the therapeutic management of OP poisoning. However, its use has been associated with several unwanted effects including, sedation, amnesia, and in the large doses used for such treatment, respiratory depression. Moreover, protracted administration of diazepam has been associated with tolerance and dependence liabilities. In this study, we compared the efficacy and safety of diazepam (full allosteric modulator of GABA action) to that of imidazemil (partial, selective allosteric modulator of GABA action) as preventive treatment against diisopropyl fluorophosphate (DFP)-induced convulsions and mortality. Our results show that imidazenil is more potent and efficacious than diazepam in protecting rats against DFP-induced convulsions and death. Moreover, imidazenil was effective at doses (1 and 0.5 mg/kg) we have previously shown to be devoid of sedation, amnesia, respiratory depression, or tolerance and/or dependence. In contrast, diazepam was effective at doses (5 and 2.5 mg/kg) that produce sedation, amnesia, and ataxia. Furthermore, the combination of imidazenil with atropine was more potent and efficacious than that with diazepam. (C) 2003 Elsevier Ltd. All rights reserved.