RT Journal Article SR Electronic T1 Pentazocine-Induced Antinociception Is Mediated Mainly by μ-Opioid Receptors and Compromised by κ-Opioid Receptors in Mice JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 579 OP 587 DO 10.1124/jpet.111.179879 VO 338 IS 2 A1 Haihua Shu A1 Masakazu Hayashida A1 Hideko Arita A1 Wenqi Huang A1 Hui Zhang A1 Ke An A1 Guiyun Wu A1 Kazuo Hanaoka YR 2011 UL http://jpet.aspetjournals.org/content/338/2/579.abstract AB 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 μ-opioid receptor antagonist clocinnamox mesylate (C-CAM) (5 mg · kg−1), a κ-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 μ-opioid receptors, but at high doses, this μ-opioid receptor-mediated antinociception is antagonized by concomitant activation of κ-opioid receptors. This provides the first reasonable hypothesis to explain the ceiling effects of pentazocine analgesia characterized by a biphasic dose response.