一种κ-δ双阿片受体激动剂在小鼠福尔马林试验中的抗伤害感受作用
The antinociceptive effects of a dual kappa-delta opioid receptor agonist in the mouse formalin test.
作者信息
Ulker Esad, Toma Wisam, White Alyssa, Uprety Rajendra, Majumdar Susruta, Damaj M Imad
机构信息
Department of Pharmacology and Toxicology and Translational Research Initiative for Pain and Neuropathy, Virginia Commonwealth University, Virginia Commonwealth University, Richmond, Virginia.
bDepartment of Neurology and Molecular Pharmacology, Memorial Sloan Kettering Cancer Center, New York.
出版信息
Behav Pharmacol. 2020 Apr;31(2&3):174-178. doi: 10.1097/FBP.0000000000000541.
Pain management is a challenging and unmet medical need. Despite their demonstrated efficacy, currently used opioid drugs and nonsteroidal anti-inflammatory drugs are frequently associated with several adverse events. The identification of new and safe analgesics is therefore needed. MP1104, an analogue of 3'-iodobenzoyl naltrexamine, is a potent nonselective full agonist at mu (MOR), kappa (KOR), and delta (DOR) opioid receptors, respectively. It was shown to possess potent antinociceptive effects in acute thermal pain assays without aversion in mice. In this study, we investigated MP1104 in the formalin test, a model of tonic pain. MP1104 (0.05, 0.1, and 1.0 mg/kg) reduced pain-like behaviors in phases I and II of the formalin test in male and female ICR mice. Pretreatment with KOR antagonist (norbinaltorphimine 10 mg/kg) and DOR antagonist (naltrindole 10 mg/kg) abolished the antinociceptive effects of MP1104 in the formalin test. These findings support the development of MP1104 for further testing in other pain models.
疼痛管理是一项具有挑战性且尚未满足的医疗需求。尽管目前使用的阿片类药物和非甾体抗炎药已证明其疗效，但它们经常与多种不良事件相关。因此，需要鉴定新的安全镇痛药。MP1104是3'-碘苯甲酰纳曲胺的类似物，分别是μ（MOR）、κ（KOR）和δ（DOR）阿片受体的强效非选择性完全激动剂。在急性热痛试验中，它显示出强效的抗伤害感受作用，且在小鼠中无厌恶反应。在本研究中，我们在福尔马林试验（一种持续性疼痛模型）中研究了MP1104。MP1104（0.05、0.1和1.0 mg/kg）可减少雄性和雌性ICR小鼠福尔马林试验I期和II期的疼痛样行为。用KOR拮抗剂（纳洛托啡胺10 mg/kg）和DOR拮抗剂（纳曲吲哚10 mg/kg）预处理可消除MP1104在福尔马林试验中的抗伤害感受作用。这些发现支持开发MP1104以在其他疼痛模型中进行进一步测试。
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