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瑞莫必利对绵羊和大鼠伤害性感受阈值变化的行为学分析

Behavioural analysis of changes in nociceptive thresholds produced by remoxipride in sheep and rats.

作者信息

Main D C, Waterman A E, Kilpatrick I C

机构信息

Department of Clinical Veterinary Science, University of Bristol, UK.

出版信息

Eur J Pharmacol. 1995 Dec 20;287(3):221-31. doi: 10.1016/0014-2999(95)00491-2.

Abstract

The antinociceptive potential of remoxipride was investigated in sheep and rats with concurrent motor function assessments. Previous studies of sheep given intravenous remoxipride have revealed increases in mechanical nociceptive thresholds. Here, further investigation in sheep demonstrated elevated thermal nociceptive thresholds with no effect on subjectively assessed sedation or motor impairment scores. However, in rats, the dose of remoxipride (100 mg/kg i.p.) required to produce nociceptive thresholds similar to those elicited by morphine (30 mg/kg i.p.), itself reduced rotarod performance. Medetomidine (200 micrograms/kg i.p.) evoked sedation without influencing rotarod performance or antinociception. The antinociceptive, motor deficit and cataleptogenic actions of remoxipride were similar to those induced by two other dopamine antagonists, haloperidol (5 mg/kg) and raclopride (16 mg/kg i.p). Tocainide (100 mg/kg i.p.) induced thermal antinociception with normal rotarod performance and no catalepsy suggesting that Na+ channel blockade by remoxipride is not responsible for the changes in nociceptive thresholds. This study emphasizes the importance of motor function assessment during acute antinociceptive testing.

摘要

通过同步进行运动功能评估,研究了瑞莫必利在绵羊和大鼠中的抗伤害感受潜力。此前对静脉注射瑞莫必利的绵羊的研究显示,其机械性伤害感受阈值升高。在此,对绵羊的进一步研究表明,热伤害感受阈值升高,且对主观评估的镇静或运动损伤评分无影响。然而,在大鼠中,产生与吗啡(腹腔注射30mg/kg)所引发的类似伤害感受阈值所需的瑞莫必利剂量(腹腔注射100mg/kg)本身会降低转棒试验表现。美托咪定(腹腔注射200μg/kg)引起镇静,但不影响转棒试验表现或抗伤害感受。瑞莫必利的抗伤害感受、运动功能缺陷和致僵作用与另外两种多巴胺拮抗剂氟哌啶醇(5mg/kg)和雷氯必利(腹腔注射16mg/kg)所诱导的作用相似。妥卡尼(腹腔注射100mg/kg)诱导热抗伤害感受,转棒试验表现正常且无僵住症,这表明瑞莫必利对钠通道的阻断并非伤害感受阈值变化的原因。这项研究强调了在急性抗伤害感受测试中进行运动功能评估的重要性。

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