DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more



Pentazocine-induced antinociception is mediated mainly by mu-opioid receptors and compromised by kappa-opioid receptors in mice.

Author(s): Shu H, Hayashida M, Arita H, Huang W, Zhang H, An K, Wu G, Hanaoka K

Affiliation(s): Department of Anesthesiology, First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan 2nd Road, Guangzhou, Guangdong, 510080, China. shuhaihua@gmail.com

Publication date & source: 2011-08, J Pharmacol Exp Ther., 338(2):579-87. Epub 2011 May 4.

Publication type: Comparative Study; Research Support, Non-U.S. Gov't

Pentazocine is a widely used mixed agonist-antagonist opioid. Previous animal studies have demonstrated that pentazocine-induced antinociception displayed a ceiling effect characterized by biphasic dose response with a increasing and then descending analgesia like a bell-shaped curve. This study attempted to clarify the mechanisms underlying such dose-response relationships. ddY and C57BL/6J mice received subcutaneous injection of saline or pentazocine (3, 10, 30, 56, or 100 mg . kg(-1)), at 120 min after subcutaneous injection of saline, a mu-opioid receptor antagonist clocinnamox mesylate (C-CAM) (5 mg . kg(-1)), a kappa-opioid receptor antagonist nor-binaltorphimine (nor-BNI) (10 mg . kg(-1)), or the combination of C-CAM and nor-BNI. The antinociceptive effects of pentazocine were evaluated using tail pressure, hot plate, tail flick, and acetic acid writhing tests. Without pretreatment with an opioid receptor antagonist, the antinociceptive effects of pentazocine exhibited biphasic bell-shaped dose-response curves peaking at 30 mg . kg(-1). C-CAM completely and partly antagonized the antinociception induced by pentazocine at low (3-30 mg . kg(-1)) and high (56-100 mg . kg(-1)) doses, respectively. nor-BNI enhanced the antinociception by pentazocine at high doses and turned the later descending portion of the biphasic dose-response curves into a sigmoid curve. The combination of C-CAM and nor-BNI completely abolished the antinociception by pentazocine at all doses. Our results suggest pentazocine produces antinociception primarily via activation of mu-opioid receptors, but at high doses, this mu-opioid receptor-mediated antinociception is antagonized by concomitant activation of kappa-opioid receptors. This provides the first reasonable hypothesis to explain the ceiling effects of pentazocine analgesia characterized by a biphasic dose response.

Page last updated: 2011-12-09

-- advertisement -- The American Red Cross
 
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017