Shiga Yousuke, Minami Kouichiro, Shiraishi Munehiro, Uezono Yasuhito, Murasaki Osamu, Kaibara Muneshige, Shigematsu Akio
Department of Anesthesiology, University of Occupational and Environmental Health, School of Medicine, 1-1 Iseigaoka, Yahatanishiku, Kitakyushu, Fukuoka 807-8555, Japan.
Anesth Analg. 2002 Nov;95(5):1269-73, table of contents. doi: 10.1097/00000539-200211000-00031.
Tramadol is a widely used analgesic, but its mechanism of action is not completely understood. Muscarinic receptors are involved in neuronal function in the brain and autonomic nervous system, and much attention has been paid to these receptors as targets of analgesic drugs in the central nervous system. In this study, we investigated the effects of tramadol on type-3 muscarinic (M(3)) receptors using the Xenopus oocyte expression system. Tramadol (10 nM-100 micro M) inhibited acetylcholine-induced currents in oocytes expressing M(3) receptor. Although GF109203X, a protein kinase C inhibitor, increased the basal current, it had little effect on the inhibition of acetylcholine-induced currents by tramadol. Moreover, tramadol inhibited the specific binding sites of [(3)H]quinuclidinyl benzilate. These findings suggest that tramadol at clinically relevant concentrations inhibits M(3) function via quinuclidinyl benzilate-binding sites. This may explain the modulation of neuronal function and the anticholinergic effects of tramadol.
Muscarinic receptors are involved in neuronal function and are targets of analgesic drugs. We here report that tramadol inhibits type-3 muscarinic receptors function via quinuclidinyl benzilate-binding sites at clinically relevant concentrations. These findings may explain the modulation of neuronal function and the anticholinergic effects of tramadol.
曲马多是一种广泛使用的镇痛药，但其作用机制尚未完全明确。毒蕈碱受体参与大脑和自主神经系统的神经元功能，作为中枢神经系统镇痛药的靶点，这些受体已受到广泛关注。在本研究中，我们使用非洲爪蟾卵母细胞表达系统研究了曲马多对3型毒蕈碱（M(3)）受体的影响。曲马多（10 nM - 100 μM）抑制了表达M(3)受体的卵母细胞中乙酰胆碱诱导的电流。尽管蛋白激酶C抑制剂GF109203X增加了基础电流，但对曲马多抑制乙酰胆碱诱导电流的作用影响甚微。此外，曲马多抑制了[³H]喹核醇基苯甲酸酯的特异性结合位点。这些发现表明，临床相关浓度的曲马多通过喹核醇基苯甲酸酯结合位点抑制M(3)功能。这可能解释了曲马多对神经元功能的调节作用及其抗胆碱能效应。
毒蕈碱受体参与神经元功能，是镇痛药的靶点。我们在此报告，临床相关浓度的曲马多通过喹核醇基苯甲酸酯结合位点抑制3型毒蕈碱受体功能。这些发现可能解释曲马多对神经元功能的调节作用及其抗胆碱能效应。
