可乐定与非甾体抗炎药抗伤害感受相互作用的等效线图分析

Isobolographic analysis of the antinociceptive interactions of clonidine with nonsteroidal anti-inflammatory drugs.

作者信息

Miranda H F, Pinardi G

机构信息

Pharmacology Program, ICBM, Faculty of Medicine, University of Chile, P.O. Box 70,000, Santiago 7, Chile.

出版信息

Pharmacol Res. 2004 Sep;50(3):273-8. doi: 10.1016/j.phrs.2004.02.008.

DOI:10.1016/j.phrs.2004.02.008

PMID:15225670

Abstract

The present study was undertaken to characterize the interactions between nonsteroidal anti-inflammatory drugs and the alpha(2)-adrenoceptor agonist clonidine in an acute nociceptive test. The writhing test was selected as a model of acute visceral pain. Isobolograms were constructed to assess the interactions of clonidine and each nonsteroidal anti-inflammatory drugs, when coadministered intraperitoneally and intrathecally (i.t.). The simultaneous intraperitoneal administration of fixed ratios of ED(50) fractions of all nonsteroidal anti-inflammatory drugs (naproxen, piroxicam, paracetamol, dipyrone or metamizol and nimesulide) combined with clonidine resulted in synergistic interactions. The same combinations administered intrathecally were additive. The synergistic interactions between systemic nonsteroidal anti-inflammatory drugs and clonidine may involve supraspinal mechanisms.

摘要

本研究旨在通过急性伤害感受试验来描述非甾体抗炎药与α₂-肾上腺素能受体激动剂可乐定之间的相互作用。扭体试验被选作急性内脏痛模型。构建等效应线图以评估可乐定与每种非甾体抗炎药经腹腔内和鞘内联合给药时的相互作用。同时腹腔内给予所有非甾体抗炎药（萘普生、吡罗昔康、对乙酰氨基酚、安乃近或安替比林以及尼美舒利）的ED₅₀分数的固定比例与可乐定联合使用会产生协同相互作用。鞘内给予相同组合则具有相加作用。全身用非甾体抗炎药与可乐定之间的协同相互作用可能涉及脊髓上机制。