Pentazocine-induced antinociception is mediated mainly by μ-opioid receptors and compromised by κ-opioid receptors in mice. 2011

Haihua Shu, and Masakazu Hayashida, and Hideko Arita, and Wenqi Huang, and Hui Zhang, and Ke An, and Guiyun Wu, and Kazuo Hanaoka
Department of Anesthesiology, First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan 2nd Road, Guangzhou, Guangdong, 510080, China. shuhaihua@gmail.com

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.

UI MeSH Term Description Entries
D008297 Male Males
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D009292 Narcotic Antagonists Agents inhibiting the effect of narcotics on the central nervous system. Competitive Opioid Antagonist,Narcotic Antagonist,Opioid Antagonist,Opioid Antagonists,Opioid Receptor Antagonist,Opioid Reversal Agent,Competitive Opioid Antagonists,Opioid Receptor Antagonists,Opioid Reversal Agents,Agent, Opioid Reversal,Agents, Opioid Reversal,Antagonist, Competitive Opioid,Antagonist, Narcotic,Antagonist, Opioid,Antagonist, Opioid Receptor,Antagonists, Competitive Opioid,Antagonists, Narcotic,Antagonists, Opioid,Antagonists, Opioid Receptor,Opioid Antagonist, Competitive,Opioid Antagonists, Competitive,Receptor Antagonist, Opioid,Receptor Antagonists, Opioid,Reversal Agent, Opioid,Reversal Agents, Opioid
D010147 Pain Measurement Scales, questionnaires, tests, and other methods used to assess pain severity and duration in patients or experimental animals to aid in diagnosis, therapy, and physiological studies. Analgesia Tests,Analogue Pain Scale,Formalin Test,McGill Pain Questionnaire,Nociception Tests,Pain Assessment,Pain Intensity,Pain Severity,Tourniquet Pain Test,Visual Analogue Pain Scale,Analog Pain Scale,Assessment, Pain,McGill Pain Scale,Visual Analog Pain Scale,Analgesia Test,Analog Pain Scales,Analogue Pain Scales,Formalin Tests,Intensity, Pain,Measurement, Pain,Nociception Test,Pain Assessments,Pain Intensities,Pain Measurements,Pain Questionnaire, McGill,Pain Scale, Analog,Pain Scale, Analogue,Pain Scale, McGill,Pain Severities,Pain Test, Tourniquet,Questionnaire, McGill Pain,Scale, Analog Pain,Scale, Analogue Pain,Scale, McGill Pain,Severity, Pain,Test, Analgesia,Test, Formalin,Test, Nociception,Test, Tourniquet Pain,Tests, Nociception,Tourniquet Pain Tests
D010423 Pentazocine The first mixed agonist-antagonist analgesic to be marketed. It is an agonist at the kappa and sigma opioid receptors and has a weak antagonist action at the mu receptor. (From AMA Drug Evaluations Annual, 1991, p97) Fortral,Lexir,Pentazocine Hydrochloride,Pentazocine Lactate,Talwin,Hydrochloride, Pentazocine,Lactate, Pentazocine
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D000701 Analgesics, Opioid Compounds with activity like OPIATE ALKALOIDS, acting at OPIOID RECEPTORS. Properties include induction of ANALGESIA or NARCOSIS. Opioid,Opioid Analgesic,Opioid Analgesics,Opioids,Full Opioid Agonists,Opioid Full Agonists,Opioid Mixed Agonist-Antagonists,Opioid Partial Agonists,Partial Opioid Agonists,Agonist-Antagonists, Opioid Mixed,Agonists, Full Opioid,Agonists, Opioid Full,Agonists, Opioid Partial,Agonists, Partial Opioid,Analgesic, Opioid,Full Agonists, Opioid,Mixed Agonist-Antagonists, Opioid,Opioid Agonists, Full,Opioid Agonists, Partial,Opioid Mixed Agonist Antagonists,Partial Agonists, Opioid
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D017450 Receptors, Opioid, mu A class of opioid receptors recognized by its pharmacological profile. Mu opioid receptors bind, in decreasing order of affinity, endorphins, dynorphins, met-enkephalin, and leu-enkephalin. They have also been shown to be molecular receptors for morphine. Morphine Receptors,Opioid Receptors, mu,Receptors, Morphine,Receptors, mu,Receptors, mu Opioid,mu Receptors,Morphine Receptor,mu Opioid Receptor,mu Receptor,Opioid Receptor, mu,Receptor, Morphine,Receptor, mu,Receptor, mu Opioid,mu Opioid Receptors
D017473 Receptors, Opioid, kappa A class of opioid receptors recognized by its pharmacological profile. Kappa opioid receptors bind dynorphins with a higher affinity than endorphins which are themselves preferred to enkephalins. Opioid Receptors, kappa,Receptors, kappa,Receptors, kappa Opioid,kappa Receptors,kappa Opioid Receptor,kappa Receptor,Opioid Receptor, kappa,Receptor, kappa,Receptor, kappa Opioid,kappa Opioid Receptors

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