Cannabinoid Receptor Agonists for Treatment of Chronic Pain

大麻素受体激动剂治疗慢性疼痛

基本信息

批准号：
8591282
负责人：
Anuradha Mahadevan
金额：
$ 27.93万
依托单位：
ORGANIX, INC.
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-01 至 2016-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8591282
关键词：
2-cyclopentyl-5-(5-isoquinolylsulfonyl)-6-nitro-1H-benzo(D)imidazole Address Adverse effects Affinity Agonist Animals Behavior Binding Biological Assay CNR1 gene CNR2 gene Cannabinoids Chronic Development Disease Drug Targeting Expenditure Formalin Goals Health Immune In Vitro Inflammation Injury Lead Legal patent Licensing Lidocaine Patch Ligands Mediating Medical Modeling Modification Nervous system structure Neuraxis Neuropathy Nociception Norepinephrine Opioid Opioid Analgesics Outcome Pain Pain management Patients Penetration Peripheral Persistent pain Pharmaceutical Preparations Pharmacologic Substance Phase Population Positioning Attribute Receptor Activation Research Seizures Serotonin Side Stimulus Structure-Activity Relationship Testing Therapeutic Thermal Hyperalgesias Tissues Tramadol Work allodynia analog base cannabinoid receptor chronic neuropathic pain chronic pain commercialization design functional group gabapentin improved in vivo inflammatory neuropathic pain inflammatory pain inhibitor/antagonist lipophilicity medical appointment mouse model novel painful neuropathy productivity loss receptor binding response sciatic nerve uptake

项目摘要

DESCRIPTION (provided by applicant): Chronic pain can result from various disease conditions and about 45% of the U. S. population seeks medical help for treatment of pain. Neuropathic pain is a type of chronic pain which is very difficult to treat, and most patients do not get adequate relief. A promising therapeutic drug target for the treatment of inflammation and pain is the cannabinoid CB2 receptor. In Phase I of this proposal our focus will be on the structural optimization of our lead template to develop a high efficacy CB2 selective agonist with pain suppression potential and with no CNS side effects. Established in vivo and in vitro pharmacological assays will be used to identify compounds that: 1) are highly selective for CB2 over CB1 receptors; 2) possess high efficacy and high potency in binding and activating the CB2 receptor; 3) possess high efficacy in reversing allodynia (i.e., nociceptive behavior in response to normally non-noxious stimuli); and 4) lack cannabimimetic side effects in whole animals that are typically indicative of CB1 receptor activation. The long-term objective of this proposal is to develop a novel drug for treatment of chronic pain which is both safe and effective.

描述（由申请人提供）：慢性疼痛可能由多种疾病引起，大约 45% 的美国人寻求医疗帮助来治疗疼痛。神经性疼痛是一种非常难以治疗的慢性疼痛，大多数患者无法得到足够的缓解。大麻素 CB2 受体是治疗炎症和疼痛的一个有前途的治疗药物靶点。在该提案的第一阶段，我们的重点将是先导模板的结构优化，以开发具有疼痛抑制潜力且无中枢神经系统副作用的高效 CB2 选择性激动剂。已建立的体内和体外药理学测定将用于鉴定具有以下特征的化合物： 1) 对 CB2 受体的选择性高于 CB1 受体； 2)具有高效能和高效能的结合和激活CB2受体； 3) 在逆转异常性疼痛方面具有高效能（即，对正常非伤害性刺激做出反应的伤害性行为）； 4) 在整个动物中不存在通常表明 CB1 受体激活的大麻模拟副作用。该提案的长期目标是开发一种安全有效的治疗慢性疼痛的新药。