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Peripheral tachykinin receptors as potential therapeutic targets in visceral diseases.

机译:周围速激肽受体是内脏疾病的潜在治疗靶标。

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摘要

More than 10 years of intensive preclinical investigation of selective tachykinin (TK) receptor antagonists has provided a rationale to the speculation that peripheral neurokinin (NK)-1, -2 and -3 receptors may be involved in the pathophysiology of various human diseases at the visceral level. In the airways, despite promising effects in animal models of asthma, pilot clinical trials with selective NK-1 or -2 receptor antagonists in asthmatics have been ambiguous, whereas the potential antitussive effects of NK-1, -2 or -3 antagonists have not yet been verified in humans. In the gastrointestinal (GI) tract, irritable bowel syndrome (IBS) and pancreatitis are appealing targets for peripherally-acting NK-1 and -2 antagonists, respectively. In the genito-urinary tract, NK-1 receptor antagonists could offer some protection against nephrotoxicity and cytotoxicity induced by chemotherapeutic agents, whereas NK-2 receptor antagonists appear to be promising new agents for the treatment of neurogenic bladder hyperreflexia. Finally, there is preclinical evidence for hypothesising an effect of NK-3 receptor antagonists on the cardiovascular disturbance that characterises pre-eclampsia. Other more speculative applications are also mentioned.
机译:超过10年的选择性速激肽(TK)受体拮抗剂的深入临床前研究为推测外周神经激肽(NK)-1,-2和-3受体可能参与多种人类疾病的病理生理学提供了理论依据。内脏水平。在气道中,尽管在哮喘的动物模型中产生了令人鼓舞的效果,但在哮喘患者中使用选择性NK-1或-2受体拮抗剂的先导临床试验尚不明确,而NK-1,-2或-3拮抗剂的潜在镇咳作用尚未尚未在人类中得到验证。在胃肠道(GI)中,肠易激综合症(IBS)和胰腺炎分别是作用于外周的NK-1和-2拮抗剂的诱人靶标。在生殖泌尿道中,NK-1受体拮抗剂可提供针对化学治疗剂引起的肾毒性和细胞毒性的某些保护作用,而NK-2受体拮抗剂似乎是有望治疗神经性膀胱反射亢进的新药。最后,有临床前证据可推测NK-3受体拮抗剂对子痫前期所致心血管疾病的作用。还提到了其他更具投机性的应用程序。

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