Sałat Kinga, Jakubowska Anna, Kulig Katarzyna
Jagiellonian University, Chair of Pharmacodynamics, Faculty of Pharmacy , Medyczna 9 St., 30-688 Kraków , Poland.
Expert Opin Investig Drugs. 2015 Jun;24(6):837-44. doi: 10.1517/13543784.2015.1036985. Epub 2015 Apr 12.
Pain is a syndrome of various clinical disorders, which arises from various pathological conditions and which presents significant challenges in both its diagnosis and treatment. There is currently a strong medical demand to develop new therapies with a higher efficacy and a better tolerability profile.
In this review, the authors report on the available data for the pharmacological properties of cebranopadol (GRT6005), a first in-class, potent analgesic compound which acts as an agonist of nociceptin/orphanin FQ peptide (NOP) and opioid receptors. They highlight the in vitro receptor binding studies, as well as the in vivo preclinical results on the analgesic efficacy of cebranopadol obtained in several rodent pain models. The authors also briefly summarize the available data from clinical trials with cebranopadol.
Cebranopadol displays analgesic, antiallodynic and antihyperalgesic properties in several rat models of acute nociceptive, inflammatory, cancer and neuropathic pain. In contrast to classical opioids, it has a higher analgesic potency in models of neuropathic pain than in acute nociceptive pain. Even at higher analgesic doses, cebranopadol does not induce motor coordination deficits or respiratory depression in rats. Hence, it seems to possess a broader therapeutic window than classical opioids. While it is particularly interesting as a novel, potent bifunctional agonist of NOP/opioid receptors, the outcome of its ongoing and planned clinical trials will be crucial for its future development and potential application in humans.
疼痛是一种由多种临床疾病引起的综合征，源于各种病理状况，在诊断和治疗方面都带来了重大挑战。目前，医学上迫切需要开发疗效更高、耐受性更好的新疗法。
在本综述中，作者报告了cebranopadol（GRT6005）的药理学特性的现有数据，cebranopadol是一种一流的强效镇痛化合物，作为痛敏肽/孤啡肽FQ肽（NOP）和阿片受体的激动剂发挥作用。他们强调了体外受体结合研究，以及在几种啮齿动物疼痛模型中获得的cebranopadol镇痛效果的体内临床前结果。作者还简要总结了cebranopadol临床试验的现有数据。
cebranopadol在几种急性伤害性、炎症性、癌症性和神经性疼痛的大鼠模型中表现出镇痛、抗痛觉过敏和抗痛觉超敏特性。与传统阿片类药物不同，它在神经性疼痛模型中的镇痛效力高于急性伤害性疼痛模型。即使在较高的镇痛剂量下，cebranopadol也不会在大鼠中引起运动协调缺陷或呼吸抑制。因此，它似乎比传统阿片类药物具有更宽的治疗窗口。虽然它作为一种新型强效NOP/阿片受体双功能激动剂特别有趣，但其正在进行和计划中的临床试验结果对其未来发展和在人类中的潜在应用至关重要。
