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The endocannabinoid system as an emerging target of pharmacotherapy.
Pharmacological Reviews ( IF 19.3 ) Pub Date : 2006-09-01 , DOI: 10.1124/pr.58.3.2
Pál Pacher 1 , Sándor Bátkai , George Kunos
Affiliation  

The recent identification of cannabinoid receptors and their endogenous lipid ligands has triggered an exponential growth of studies exploring the endocannabinoid system and its regulatory functions in health and disease. Such studies have been greatly facilitated by the introduction of selective cannabinoid receptor antagonists and inhibitors of endocannabinoid metabolism and transport, as well as mice deficient in cannabinoid receptors or the endocannabinoid-degrading enzyme fatty acid amidohydrolase. In the past decade, the endocannabinoid system has been implicated in a growing number of physiological functions, both in the central and peripheral nervous systems and in peripheral organs. More importantly, modulating the activity of the endocannabinoid system turned out to hold therapeutic promise in a wide range of disparate diseases and pathological conditions, ranging from mood and anxiety disorders, movement disorders such as Parkinson's and Huntington's disease, neuropathic pain, multiple sclerosis and spinal cord injury, to cancer, atherosclerosis, myocardial infarction, stroke, hypertension, glaucoma, obesity/metabolic syndrome, and osteoporosis, to name just a few. An impediment to the development of cannabinoid medications has been the socially unacceptable psychoactive properties of plant-derived or synthetic agonists, mediated by CB(1) receptors. However, this problem does not arise when the therapeutic aim is achieved by treatment with a CB(1) receptor antagonist, such as in obesity, and may also be absent when the action of endocannabinoids is enhanced indirectly through blocking their metabolism or transport. The use of selective CB(2) receptor agonists, which lack psychoactive properties, could represent another promising avenue for certain conditions. The abuse potential of plant-derived cannabinoids may also be limited through the use of preparations with controlled composition and the careful selection of dose and route of administration. The growing number of preclinical studies and clinical trials with compounds that modulate the endocannabinoid system will probably result in novel therapeutic approaches in a number of diseases for which current treatments do not fully address the patients' need. Here, we provide a comprehensive overview on the current state of knowledge of the endocannabinoid system as a target of pharmacotherapy.

中文翻译:

内源性大麻素系统作为药物治疗的新兴目标。

最近对大麻素受体及其内源性脂质配体的鉴定引发了探索内源性大麻素系统及其在健康和疾病中的调节功能的研究呈指数增长。通过引入选择性大麻素受体拮抗剂和内源性大麻素代谢和运输抑制剂,以及缺乏大麻素受体或内源性大麻素降解酶脂肪酸酰胺水解酶的小鼠,极大地促进了此类研究。在过去的十年中,内源性大麻素系统与中枢和周围神经系统以及周围器官中越来越多的生理功能有关。更重要的是,调节内源性大麻素系统的活性被证明对多种不同的疾病和病理状况具有治疗前景,包括情绪和焦虑障碍、帕金森病和亨廷顿病等运动障碍、神经性疼痛、多发性硬化症和脊柱疾病脊髓损伤、癌症、动脉粥样硬化、心肌梗塞、中风、高血压、青光眼、肥胖/代谢综合征和骨质疏松症等。大麻素药物开发的一个障碍是由 CB(1) 受体介导的植物源或合成激动剂的社会不可接受的精神活性特性。然而,当通过CB(1)受体拮抗剂治疗达到治疗目的时,例如在肥胖症中,这个问题不会出现,并且当内源性大麻素的作用通过阻断其代谢或运输而间接增强时,也可能不存在。使用缺乏精神活性特性的选择性 CB(2) 受体激动剂可能是治疗某些疾病的另一种有希望的途径。通过使用成分受控的制剂以及仔细选择剂量和给药途径,也可以限制植物源大麻素的滥用潜力。越来越多的针对调节内源性大麻素系统的化合物的临床前研究和临床试验可能会为许多目前的治疗方法不能完全满足患者需求的疾病带来新的治疗方法。在这里,我们全面概述了内源性大麻素系统作为药物治疗目标的知识现状。
更新日期:2019-11-01
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