Homeostatic bioenergetic network regulation - a novel concept to avoid pharmacoresistance in epilepsy.
Homeostatic bioenergetic network regulation - a novel concept to avoid pharmacoresistance in epilepsy.
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DOI：
10.1517/17460441.2011.575777
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发表时间：
2011-07
影响因子：
6.3
通讯作者：
Geiger JD
中科院分区：
文献类型：
--
作者：
Boison D;Masino SA;Geiger JD
尽管癫痫是最常见的神经系统疾病之一，但三分之一的癫痫患者无法用现有的抗癫痫药物进行充分治疗。常规药物治疗失败的重要原因之一是许多形式的癫痫中产生了抗药性。耐药性问题要求制定新的概念策略，以改善未来的药物开发工作。完成了对最近关于癫痫药物耐药性的文献的全面审查，并选择了一些例子来强调癫痫药物耐药性的机制，并证明这些机制研究结果如何改善药物耐药性癫痫的治疗。读者将获得一个彻底的了解癫痫的抗药性和传统药物开发策略的局限性的赞赏。传统的药物开发工作旨在通过增强作用于特定下游靶点的药物的选择性来实现症状控制的特异性;这种概念性策略承担了产生抗药性的不适当风险。调节稳态生物能网络调节是一种新的概念策略，通过动员多种内源性生化和受体依赖性分子途径协同影响整个神经网络。在我们的专家意见中，我们得出结论，稳态生物能量网络调节可能因此被用作控制耐药性癫痫发作的创新策略。最近的局灶性腺苷增强策略支持这种策略的可行性。
Despite epilepsy being one of the most prevalent neurological disorders, one third of all patients with epilepsy cannot adequately be treated with available antiepileptic drugs. One of the significant causes for the failure of conventional pharmacotherapeutic treatment is the development of pharmacoresistance in many forms of epilepsy. The problem of pharmacoresistance has called for the development of new conceptual strategies that improve future drug development efforts. A thorough review of the recent literature on pharmacoresistance in epilepsy was completed and select examples were chosen to highlight the mechanisms of pharmacoresistance in epilepsy and to demonstrate how those mechanistic findings might lead to improved treatment of pharmacoresistant epilepsy. The reader will gain a thorough understanding of pharmacoresistance in epilepsy and an appreciation of the limitations of conventional drug development strategies. Conventional drug development efforts aim to achieve specificity of symptom control by enhancing the selectivity of drugs acting on specific downstream targets; this conceptual strategy bears the undue risk of development of pharmacoresistance. Modulation of homeostatic bioenergetic network regulation is a novel conceptual strategy to affect whole neuronal networks synergistically by mobilizing multiple endogenous biochemical and receptor-dependent molecular pathways. In our expert opinion we conclude that homeostatic bioenergetic network regulation might thus be used as an innovative strategy for the control of pharmacoresistant seizures. Recent focal adenosine augmentation strategies support the feasibility of this strategy.
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