Profiles of the Antinociceptive Effect of R - 84760, a Selective κ - Opioid Receptor Agonist, in the Formalin Test in Mice

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概要

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• The antinociceptive effect of a selective κ-opioid receptor agonist R-84760, (3<I>R</I>)-3-(1-pyrrolidinylmethyl)-4-[(1<I>S</I>)-5, 6-dichloro-1-indancarbonyl]-tetrahydro-1, 4-thiazine hydrochloride, in the second phase of the formalin test, a model of tonic pain, was examined in mice. R-84760 had a 2700 times more potent antinociceptive effect than morphine. The effect of R-84760 was antagonized by subcutaneously administered nor-binaltorphimine, a κ-selective opioid receptor antagonist. Both intracerebroventricularly and intrathecally administered nor-binaltorphimine partially antagonized the antinociceptive effect of R-84760. Intrathecally administered phentolamine, an α-adrenoceptor antagonist, attenuated and desipramine, a noradrenaline reuptake inhibitor, augmented the antinociceptive effect of R-84760. Intrathecally administered noradrenaline attenuated the nociceptive response in the second phase of the formalin test. Intrathecally administered (±)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), an <I>N</I>-methyl-D-aspartate (NMDA)-receptor antagonist, reduced and <I>threo</I>-β-hydroxyaspartate, a reuptake inhibitor of glutamate, augmented the second phase nociceptive response. However, R-84760 did not influence the intrathecally injected NMDA-induced nociceptive response. These results suggest the following: R-84760 produces an extremely potent antinociceptive effect against tonic pain through the κ-opioid receptors; the sites of action of subcutaneously administered R-84760 are the supraspinal and spinal loci in the central nervous system; and a part of the mechanism of the antinociceptive effect of R-84760 is activation of the descending noradrenergic pathway.

• 社団法人 日本薬理学会の論文
• 1995-05-01

著者

• FUJIBAYASHI Kenji

  Biological Research Laboratories, Sankyo Co., Ltd.,

• Iizuka Yoshio

  Biological Research Laboratories Sankyo Co. Ltd.

• Fujibayashi Kenji

  Biological Research Laboratories Sankyo Co. Ltd.

関連論文

• Antinociceptive Effect and Enzymatic Degradation of Endomorphin-1 in Newborn Rat Spinal Cord
• Pharmacological Characterization of Capsaicin-Induced Body Movement of Neonatal Rat
• Profiles of the Antinociceptive Effect of R - 84760, a Selective κ - Opioid Receptor Agonist, in the Formalin Test in Mice

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