Longmore J, Hill R G, Hargreaves R J
Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Harlow, United Kingdom.
Can J Physiol Pharmacol. 1997 Jun;75(6):612-21. doi: 10.1139/cjpp-75-6-612.
The mammalian tachykinins (substance P, neurokinin A, and neurokinin B) are widely distributed throughout the central and peripheral nervous systems, where they act as neurotransmitters or neuromodulators. Historically, the tachykinins have been implicated in a wide variety of biological actions such as pain transmission, neurogenic inflammation, smooth muscle contraction, vasodilation, secretion, and activation of the immune system. Their effects are mediated via specific G-protein-coupled receptors (NK1, NK2, and NK3 receptors). The development of nonpeptide receptor antagonists revealed species differences in neurokinin-receptor pharmacology, and the recent cloning of human neurokinin receptors has led to development of compounds with optimized affinity for the human target receptor. The neurokinin-receptor antagonists have been used in preclinical experiments to confirm the physiological roles of the tachykinins. Importantly, it is now recognised that these agents can inhibit the actions of tachykinins released from peripheral nerves, and for the NK1-receptor antagonists (the most widely studied class of neurokinin-receptor antagonists) central sites of action have also been demonstrated. These studies support the development of neurokinin-receptor antagonists as potentially exploitable drug therapies in humans, particularly in the treatment of pain and emesis.
哺乳动物速激肽（P物质、神经激肽A和神经激肽B）广泛分布于中枢和外周神经系统，在这些部位它们作为神经递质或神经调质发挥作用。从历史上看，速激肽与多种生物学作用有关，如疼痛传递、神经源性炎症、平滑肌收缩、血管舒张、分泌以及免疫系统激活。它们的作用是通过特定的G蛋白偶联受体（NK1、NK2和NK3受体）介导的。非肽类受体拮抗剂的研发揭示了神经激肽受体药理学中的种属差异，而最近人类神经激肽受体的克隆导致了对人类靶受体具有优化亲和力的化合物的开发。神经激肽受体拮抗剂已用于临床前实验，以证实速激肽的生理作用。重要的是，现在人们认识到这些药物可以抑制外周神经释放的速激肽的作用，对于NK1受体拮抗剂（研究最广泛的一类神经激肽受体拮抗剂），其作用的中枢位点也已得到证实。这些研究支持将神经激肽受体拮抗剂开发为可能在人类中可利用的药物疗法，特别是在疼痛和呕吐的治疗中。
