Tramadol antinociception is potentiated by clonidine through 伪₂-adrenergic and I₂-imidazoline but not by endothelin ET_A receptors in mice

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• 作者：Shridhar V. Andurkar^a ; ^{sandur@midwestern.edu} ; Liya Gendler^b ; Anil Gulati^a
• 关键词：Tramadol ; Clonidine ; Antinociception ; Adrenergic receptor ; Imidazoline receptor ; Opioid receptor ; Endothelin receptor
• 刊名：European Journal of Pharmacology
• 出版年：2012
• 期刊代码：24_00142999
• 类别：neu
• 出版时间：15 May, 2012
• 卷：683
• 期：1-3
• 页码：109-115
• 文件大小：538 K

摘要

Tramadol is a centrally acting analgesic that acts via 渭-opioid agonism and by blocking the neuronal uptake of norepinephrine and serotonin. Clonidine potentiates the antinociceptive effects of tramadol; however the receptors involved in this potentiation have not been studied. Endothelin ET_A receptor antagonists potentiate antinociceptive effects of morphine and oxycodone; however the effects of endothelin ET_A receptor antagonists on tramadol antinociception have not been evaluated. This study was conducted to determine the effect of clonidine on tramadol antinociception; the role of opioid, 伪₂-adrenergic and I₂-imidazoline receptors in clonidine potentiation of tramadol antinociception; and the effect of endothelin ET_A receptor antagonists in modulating tramadol antinociception. Antinociceptive (tail-flick and hot-plate) latencies were measured in male Swiss Webster mice treated with tramadol; clonidine plus tramadol; or antagonists plus tramadol. Mice were pretreated with naloxone (opioid antagonist), yohimbine (伪₂-adrenoceptor antagonist), idazoxan (伪₂-adrenoceptor/I₂-imidazoline antagonist), BMS182874 or BQ123 (endothelin ET_A receptor antagonists) to study the involvement of these receptors. Tramadol produced a dose dependent increase in antinociceptive latencies. Tramadol antinociception was partially blocked by naloxone but not by yohimbine or idazoxan. Clonidine potentiated tramadol antinociception; potentiation was blocked by naloxone, yohimbine and idazoxan. Idazoxan produced a more pronounced blockade of potentiation than yohimbine. BMS182874 or BQ123 had no effect on tramadol antinociception, indicating that endothelin ET_A receptors are not involved in tramadol antinociception in mice. Results demonstrate the involvement of opioid but not 伪₂-adrenergic/I₂-imidazoline receptors in tramadol antinociception and that opioid, 伪₂-adrenergic and I₂-imidazoline receptors are involved in clonidine potentiation of tramadol antinociception.