Keïta H, Kayser V, Guilbaud G
Unité de Recherches de Physiopharmacologie du Système nerveux, I.N.S.E.R.M. U 161, Paris, France.
Eur J Pharmacol. 1995 Apr 24;277(2-3):275-80. doi: 10.1016/0014-2999(95)00122-2.
The antinociceptive effect of intraplantar (i.pl.) ICI 204448 ((R,S)-N-[2-(N-methyl-3,4-dichloro-phenylacetamido)-2-(3-carbox yph enyl)- ethyl]pyrrolidine hydrochloride)) (20, 30, 40 and 50 micrograms), a kappa-opioid receptor agonist which has limited access to the central nervous system, was studied in a well-established rat model of peripheral mononeuropathy produced by moderate constriction of the sciatic nerve. Vocalization thresholds to paw pressure were used as a nociceptive test. On the injected nerve-injured paw, ICI 204448 at 20 and 30 micrograms had no significant effect, but higher doses (40 micrograms) produced a significant antinociceptive effect, which plateaued at 50 micrograms. By contrast, no antinociceptive effect was observed on the contralateral paw. The effect of ICI 204448 (40 micrograms) was significantly antagonised by the specific kappa-opioid receptor antagonist nor-binaltorphimine (20 and 30 micrograms), when co-injected in the nerve-injured paw.
在一种通过坐骨神经适度压迫建立的外周单神经病大鼠模型中，研究了足底注射（i.pl.）ICI 204448（（R，S）-N-[2-（N-甲基-3,4-二氯苯基乙酰胺基）-2-（3-羧基苯基）-乙基]吡咯烷盐酸盐）（20、30、40和50微克）的抗伤害感受作用，该物质是一种进入中枢神经系统受限的κ-阿片受体激动剂。将对爪部压力的发声阈值用作伤害感受测试。在注射侧的神经损伤爪上，20和30微克的ICI 204448没有显著作用，但更高剂量（40微克）产生了显著的抗伤害感受作用，在50微克时达到平稳状态。相比之下，在对侧爪上未观察到抗伤害感受作用。当在神经损伤爪中共注射时，特异性κ-阿片受体拮抗剂去甲纳曲酮（20和30微克）显著拮抗了ICI 204448（40微克）的作用。
