Novel K-opioid receptor agonist MB-1C-OH produces potent analgesia with less depression and sedation

• Published in: 中国药理学报：英文版 no. 5; pp. 565 - 571
• Main Author: Le-shaZHANG Jun WANG Jian-chun CHEN Yi-min TAO Yu-hua WANG Xue-jun XU Jie CHEN Yun-gen XU Tao XI Xiao-wu HU Yu-jun WANG Jing-gen LIU
• Format: Journal Article
• Language: English
• Published: 2015
• Subjects: GTPγS; 受体拮抗剂; 受体激动剂; 抑郁症; 福尔马林试验; 镇痛; 镇静; 阿片受体
• ISSN: 1671-4083; 1745-7254

Aim： To characterize the pharmacological profiles of a novel K-opioid receptor agonist MB-1C-OH. Methods： [3H]diprenorphine binding and [35S]GTPyS binding assays were performed to determine the agonistic properties of MB-lC-OH Hot plate, tail flick, acetic acid-induced writhing, and formalin tests were conducted in mice to evaluate the antinociceptive actions. Forced swimming and rotarod tests of mice were used to assess the sedation and depression actions. Results： In [3H]diprenorphine binding assay, MB-lC-OH did not bind to p- and 6-opioid receptors at the concentration of 100 μmol/L, but showed a high affinity for κ-opioid receptor （K1=35 nmol/L）. In [35S]GTPγS binding assay, the compound had an Emax of 98% and an ECso of 16.7 nmol/L for κ-opioid receptor. Subcutaneous injection of MB-lC-OH had no effects in both hot plate and tail flick tests, but produced potent antinociception in the acetic acid-induced writhing test （ED50=0.39 mg/kg）, which was antagonized by pretreatment with a selective κ-opioid receptor antagonist Nor-BNI. In the formalin test, subcutaneous injection of MB-lC-OH did not affect the flinching behavior in the first phase, but significantly inhibited that in the second phase （ED50=0.87 mg/kg）. In addition, the sedation or depression actions of MB-lC-OH were about 3-fold weaker than those of the classical K agonist （-）U50,488H. Conclusion： MB-1C-OH is a novel K-opioid receptor agonist that produces potent antinociception causing less sedation and depression.