The mechanisms of analgesic effects of Tramadol and Alphaxalone

点击翻译按钮获取中文摘要

The mode of action of the analgesic tramadol and alphaxalone, a neurosteroid anestheticis not well understood.We assayed the effect of tramadol and alphaxalone on [^3H]-norepinephrine ([^3H]-NE) uptake and [^3H]-desipramine binding to plasma membranes isolated from bovine adrenal medulla. We also investigated the effects of tramadol and alphaxalone on muscarinic receptors type 1 and 3, using a Xenopus oocyte expression system. Finally, we investigated the effect of tramadol and alphaxalone on catecholamine secretion, nicotine-induced calcium rises and inward currents using a Ca^<2+>-imaging system and the whole-cell patch clamp technique in bovine adrenal chromaffin cells.(1) Both tramadol and alphaxalone competitively inhibited norepinephrine transporter function at desipramine binding sites.(2) Both tramadol and alphaxalone at clinically relevant concentrations inhibits m1 and m3 function via QNB-binding sites.(3) Tramadol and alphaxalone inhibits catecholamine secretion by inhibiting nicotinic acetylcholine receptor functions and suggest that such inhibitory effects could be one of the antinociceptive mechanisms exerted by tramadol.