The antinociceptive effects of a dual kappa-delta opioid receptor agonist in the mouse formalin test.
The antinociceptive effects of a dual kappa-delta opioid receptor agonist in the mouse formalin test.
复制标题
双κ-δ阿片受体激动剂在小鼠福尔马林试验中的抗伤害作用。
DOI：
10.1097/fbp.0000000000000541
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发表时间：
2020
影响因子：
1.6
通讯作者：
Damaj,MImad
中科院分区：
文献类型：
--
作者：
Ulker,Esad;Toma,Wisam;White,Alyssa;Uprety,Rajendra;Majumdar,Susruta;Damaj,MImad
疼痛管理是一项具有挑战性且未得到满足的医疗需求。尽管其疗效已得到证实，但目前使用的阿片类药物和非甾体抗炎药经常与几种不良事件相关。因此，需要确定新的和安全的镇痛剂。MP 1104是3′-碘苯甲酰纳洛酮胺的类似物，分别是μ（莫尔）、κ（KOR）和δ（DOR）阿片受体的强效非选择性完全激动剂。在小鼠的急性热痛试验中显示其具有有效的抗伤害感受作用而无厌恶。在这项研究中，我们研究了MP 1104在福尔马林试验，强直性疼痛模型。MP 1104（0.05、0.1和1.0 mg/kg）可减少雄性和雌性ICR小鼠福尔马林测试第I和II阶段的疼痛样行为。预先给予KOR拮抗剂（norbinaltorphimine 10 mg/kg）和DOR拮抗剂（naltrindole 10 mg/kg），MP 1104的镇痛作用均消失。这些发现支持MP 1104的开发，用于在其他疼痛模型中进行进一步测试。
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.