Center for Drug Design, College of Pharmacy, Academic Health Center , University of Minnesota , Minneapolis , Minnesota 55455 , United States.
ACS Chem Neurosci. 2019 Sep 18;10(9):4007-4017. doi: 10.1021/acschemneuro.9b00230. Epub 2019 Aug 28.
Tosedostat is an inhibitor of aminopeptidases currently in phase II clinical trials for the treatment of blood-related cancers. In our laboratories, we have discovered that it possesses analgesic properties. Extensive pharmacological studies for the determination of antinociceptive effects of tosedostat are presented here. These studies have indicated that the observed analgesic effect of tosedostat stems from its action on the peripheral nervous system with minimal contribution from the central nervous system. Additionally, when given in combination with morphine, tosedostat exerts a synergistic analgesic effect resulting in a reduction of effective dosages required to achieve the same analgesic effect. With broad implications in addressing the opioid addiction crisis, these revelations attest to tosedostat being a highly valuable drug candidate with diverse pharmacological functions.
托塞司他是一种氨肽酶抑制剂，目前正处于治疗血液相关癌症的 II 期临床试验阶段。在我们的实验室中，我们已经发现它具有镇痛特性。本文介绍了为确定托塞司他的抗伤害作用而进行的广泛药理学研究。这些研究表明，托塞司他的观察到的镇痛作用源自其对周围神经系统的作用，而对中枢神经系统的贡献很小。此外，当与吗啡联合使用时，托塞司他发挥协同镇痛作用，导致达到相同镇痛效果所需的有效剂量减少。这些发现表明，托塞司他具有广泛的应用前景，可以解决阿片类药物成瘾危机，证明它是一种具有多种药理学功能的极具价值的药物候选物。
