Hospital Infantil Universitario Virgen del Rocío, Unidad de Cuidados Intensivos Pediátricos, Sevilla, Spain.
Curr Med Chem. 2011;18(12):1820-31. doi: 10.2174/092986711795496746.
The neuropeptide substance P (SP) shows a widespread distribution in both the central and peripheral nervous systems and it is known that after binding to the neurokinin-1 (NK-1) receptors, SP regulates many biological functions in the central nervous system such as emotional behaviour, stress, depression, anxiety, emesis, migraine, alcohol addiction and neurodegeneration. SP has been also implicated in pain, inflammation, hepatotoxicity and in virus proliferation, and it plays an important role in cancer (e.g., tumour cell proliferation, angiogenesis, and the migration of tumour cells for invasion and metastasis). By contrast, it is known that after binding to NK-1 receptors, NK-1 receptor antagonists specifically inhibit the above-mentioned biological functions mediated by SP. Thus, these antagonists exert an anxyolitic, antidepressant, antiemetic, antimigraine, antialcohol addiction or neuroprotector effect in the central nervous system, and they play a role in analgesic, antiinflammatory, hepatoprotector processes and in antivirus proliferation. Regarding cancer, NK-1 receptor antagonists exert an antitumour action (inducing tumour cell death by apoptosis), and induce antiangiogenesis and inhibit the migration of tumour cells. It is also known that NK-1 receptors have a widespread distribution and that they are overexpressed in tumour cells. Thus, NK-1 receptor antagonists are molecularly targeted agents. In general, current drugs have a single therapeutic effect, although less commonly they may exert several. However, the data reported above indicate that NK-1 receptor antagonists are promising drugs, exerting many therapeutic effects (the action of such antagonists is dose-dependent and, depending on the concentration, has more positive effects). In this review, we update the multiple therapeutic effects exerted by NK-1 receptor antagonists.
神经肽 P 物质（SP）在中枢和外周神经系统中广泛分布，已知其与神经激肽-1（NK-1）受体结合后，可调节中枢神经系统中的许多生物学功能，如情绪行为、应激、抑郁、焦虑、呕吐、偏头痛、酒精成瘾和神经退行性变。SP 还与疼痛、炎症、肝毒性和病毒增殖有关，在癌症中也发挥着重要作用（例如，肿瘤细胞增殖、血管生成和肿瘤细胞迁移侵袭和转移）。相反，已知与 NK-1 受体结合后，NK-1 受体拮抗剂特异性抑制 SP 介导的上述生物学功能。因此，这些拮抗剂在中枢神经系统中发挥抗焦虑、抗抑郁、止吐、抗偏头痛、抗酒精成瘾或神经保护作用，并在镇痛、抗炎、保肝过程和抗病毒增殖中发挥作用。关于癌症，NK-1 受体拮抗剂发挥抗肿瘤作用（通过凋亡诱导肿瘤细胞死亡），并诱导抗血管生成和抑制肿瘤细胞迁移。也已知 NK-1 受体分布广泛，在肿瘤细胞中过度表达。因此，NK-1 受体拮抗剂是一种靶向分子的药物。一般来说，目前的药物具有单一的治疗作用，尽管不太常见，它们可能具有多种作用。然而，上述数据表明，NK-1 受体拮抗剂是很有前途的药物，具有多种治疗作用（这些拮抗剂的作用是剂量依赖性的，并且取决于浓度，具有更多积极的影响）。在这篇综述中，我们更新了 NK-1 受体拮抗剂发挥的多种治疗作用。
