Miranda H F, Sierralta F, Pinardi G
Pharmacology Program, ICBM, Faculty of Medicine, University of Chile, Independencia 1027, Santiago 7, Chile.
Can J Physiol Pharmacol. 2002 Dec;80(12):1173-9. doi: 10.1139/y02-145.
The inhibition of cyclooxygenase enzymes by nonsteroidal anti-inflammatory drugs (NSAIDs) does not completely explain the antinociceptive efficacy of these agents. It is known that cholinergic agonists are antinociceptive, and this study evaluates the interactions between carbachol and some NSAIDs. Antinociceptive activity was evaluated in mice by the acetic acid writhing test. Dose-response curves were constructed for NSAIDs and carbachol, administered either intraperitoneally (i.p.) or intrathecally (i.t.). The interactions of carbachol with NSAIDs were evaluated by isobolographic analysis after the simultaneous administration of fixed proportions of carbachol with each NSAID. All of the drugs were more potent after spinal than after systemic administration. The combinations of NSAIDs and carbachol administered i.p. were supra-additive; however, the i.t. combinations were only additive. Isobolographic analysis of the coadministration of NSAIDs and carbachol and the fact that atropine antagonized the synergistic effect suggest that carbachol may strongly modulate the antinociceptive activity of NSAIDs; thus, central cholinergic modulation would be an additional mechanism for the antinociceptive action of NSAIDs, unrelated to prostaglandin biosynthesis inhibition.
非甾体抗炎药（NSAIDs）对环氧化酶的抑制作用并不能完全解释这些药物的镇痛效果。已知胆碱能激动剂具有镇痛作用，本研究评估了卡巴胆碱与某些NSAIDs之间的相互作用。通过醋酸扭体试验评估小鼠的镇痛活性。构建了NSAIDs和卡巴胆碱经腹腔注射（i.p.）或鞘内注射（i.t.）给药后的剂量反应曲线。在将固定比例的卡巴胆碱与每种NSAIDs同时给药后，通过等效应线图分析评估卡巴胆碱与NSAIDs的相互作用。所有药物经脊髓给药后的效力均高于全身给药。NSAIDs和卡巴胆碱经腹腔注射联合给药具有超相加作用；然而，鞘内注射联合给药仅具有相加作用。对NSAIDs和卡巴胆碱共同给药的等效应线图分析以及阿托品拮抗协同效应这一事实表明，卡巴胆碱可能强烈调节NSAIDs的镇痛活性；因此，中枢胆碱能调节将是NSAIDs镇痛作用的另一种机制，与前列腺素生物合成抑制无关。
