A Nonpeptide Oxytocin Receptor Agonist for a Durable Relief of Inflammatory Pain
A Nonpeptide Oxytocin Receptor Agonist for a Durable Relief of Inflammatory Pain
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DOI：
10.1038/s41598-020-59929-w
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发表时间：
2020-02-20
影响因子：
4.6
通讯作者：
Charlet, Alexandre
中科院分区：
文献类型：
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作者：
Hilfiger, Louis;Zhao, Qian;Charlet, Alexandre
催产素具有多种生理和社会功能，其中重要的镇痛作用。为此，催产素主要与其独特的受体结合，无论是在中枢神经系统还是在皮肤的外周伤害性末端轴突中。然而，尽管催产素具有有趣的镇痛特性，并且目前在临床中用于促进分娩，但催产素并不用于疼痛治疗。事实上，它代谢迅速，在人类和大鼠的血液循环中的半衰期估计为五分钟，在脑脊液中的半衰期约为二十分钟。此外，催产素本身还存在一些额外的缺点：缺乏特异性，口服吸收和分布极差，最后缺乏专利性。最近，第一个低分子量非肽催产素受体完全激动剂（LIT-001）已被合成，据报道外周给药后对社交互动有有益作用。在本研究中，我们报告称，在大鼠模型中单次腹腔注射 LIT-001 可长期减少炎性疼痛引起的痛觉过敏症状，为疼痛治疗的原始药物开发策略铺平了道路。
Oxytocin possesses several physiological and social functions, among which an important analgesic effect. For this purpose, oxytocin binds mainly to its unique receptor, both in the central nervous system and in the peripheral nociceptive terminal axon in the skin. However, despite its interesting analgesic properties and its current use in clinics to facilitate labor, oxytocin is not used in pain treatment. Indeed, it is rapidly metabolized, with a half-life in the blood circulation estimated at five minutes and in cerebrospinal fluid around twenty minutes in humans and rats. Moreover, oxytocin itself suffers from several additional drawbacks: a lack of specificity, an extremely poor oral absorption and distribution, and finally, a lack of patentability. Recently, a first non-peptide full agonist of oxytocin receptor (LIT-001) of low molecular weight has been synthesized with reported beneficial effect for social interactions after peripheral administration. In the present study, we report that a single intraperitoneal administration of LIT-001 in a rat model induces a long-lasting reduction in inflammatory pain-induced hyperalgesia symptoms, paving the way to an original drug development strategy for pain treatment.