CB2 Agonists for Treatment of Neuropathic Pain.

描述（由申请人提供）：神经性疼痛是一种由神经系统损伤或疾病引起的慢性疼痛状态。据估计，每年因疼痛引起的医疗支出超过1000亿美元。目前还没有药物可以预防或治愈这种毁灭性的疾病。因此，迫切需要发现有效的药物来治疗这种慢性疼痛。治疗神经性疼痛的一个有希望的药物靶点是大麻素CB2受体。在该提案的第一阶段，我们的重点将是优化我们的先导化合物，以发现一种或多种具有高受体亲和力和选择性的CB2受体激动剂。为了区分激动剂和拮抗剂的活性，将评估与CB2受体有效结合的类似物刺激[35S]GTP？年代绑定。我们的具体目标是开发一种或多种CB2先导激动剂，在神经性疼痛的动物模型中表现出良好的活性和疗效。如果这一目标在I期完成，我们将有一个候选药物在II期进一步开发。该提案的长期目标是开发一种有效且无不良副作用的神经性疼痛药物。

DESCRIPTION (provided by applicant): Neuropathic pain is a type of chronic pain state caused by injury or disease to the nervous system. Annual medical spending due to pain has been estimated to be over $100 billion. Currently there are no medications available to prevent or cure this devastating disease condition. Hence, there is an urgent need to discover effective drugs to treat this chronic pain condition. A promising drug target for neuropathic pain is the cannabinoid CB2 receptor. In phase I of this proposal our focus will be on the optimization of our lead compound to discover one or more CB2 receptor agonists with high receptor affinity and selectivity. In order to distinguish between agonist and antagonist activity, analogs that bind effectively to the CB2 receptor, will be evaluated for their ability to stimulate [35S]GTP?S binding. Our specific goal is to develop one or more lead CB2 agonists that show good activity and efficacy in an animal model for neuropathic pain. If this goal is accomplished in Phase I, we will have a drug candidate for further development in Phase II. The long-term goal of this proposal is to develop a medication for neuropathic pain that is effective and without undesirable side effects.