{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T08:02:00Z","timestamp":1777622520903,"version":"3.51.4"},"reference-count":38,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":851,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2006,10]]},"abstract":"<jats:sec><jats:title>Background and purpose:<\/jats:title><jats:p>Although tramadol is known to exhibit a local anaesthetic effect, how tramadol exerts this effect is not understood fully.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental approach:<\/jats:title><jats:p>The effects of tramadol and its metabolite mono\u2010<jats:italic>O<\/jats:italic>\u2010demethyl\u2010tramadol (M1) on compound action potentials (CAPs) were examined by applying the air\u2010gap method to frog sciatic nerves, and the results were compared with those of other local anaesthetics, lidocaine and ropivacaine.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key results:<\/jats:title><jats:p>Tramadol reduced the peak amplitude of the CAP in a dose\u2010dependent manner (IC<jats:sub>50<\/jats:sub>=2.3\u2003m<jats:sc>M<\/jats:sc>). On the other hand, M1 (1\u20132\u2003m<jats:sc>M<\/jats:sc>), which exhibits a higher affinity for<jats:italic>\u03bc<\/jats:italic>\u2010opioid receptors than tramadol, did not affect CAPs. These effects of tramadol were resistant to the non\u2010selective opioid receptor antagonist naloxone and the<jats:italic>\u03bc<\/jats:italic>\u2010opioid receptor agonist, DAMGO, did not affect CAPs. This tramadol action was not affected by a combination of the noradrenaline uptake inhibitor, desipramine, and the 5\u2010hydroxytryptamine uptake inhibitor, fluoxetine. Lidocaine and ropivacaine also concentration\u2010dependently reduced CAP peak amplitudes with IC<jats:sub>50<\/jats:sub>values of 0.74 and 0.34\u2003m<jats:sc>M<\/jats:sc>, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and implications:<\/jats:title><jats:p>These results indicate that tramadol reduces the peak amplitude of CAP in peripheral nerve fibres with a potency which is less than those of lidocaine and ropivacaine, whereas M1 has much less effect on CAPs. This action of tramadol was not produced by activation of<jats:italic>\u03bc<\/jats:italic>\u2010opioid receptors nor by inhibition of noradrenaline and 5\u2010hydroxytryptamine uptake. It is suggested that the methyl group present in tramadol but not in M1 may play an important role in producing nerve conduction block.<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic>(2006)<jats:bold>149<\/jats:bold>, 319\u2013327. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0706868\">10.1038\/sj.bjp.0706868<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1038\/sj.bjp.0706868","type":"journal-article","created":{"date-parts":[[2006,8,29]],"date-time":"2006-08-29T13:03:56Z","timestamp":1156856636000},"page":"319-327","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Tramadol, but not its major metabolite (mono\u2010<i>O<\/i>\u2010demethyl tramadol) depresses compound action potentials in frog sciatic nerves"],"prefix":"10.1111","volume":"149","author":[{"given":"R","family":"Katsuki","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T","family":"Fujita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Koga","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T","family":"Nakatsuka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Nakashima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E","family":"Kumamoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/aeg079"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1213\/01.ANE.0000135640.21229.A0"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-200109000-00013"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1213\/00000539-198906000-00005"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-199906000-00016"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(73)90196-2"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1992.tb14226.x"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1993.tb12882.x"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/284351a0"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2006.01.010"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002100000266"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1213\/00000539-198712000-00012"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/00207450590520948"},{"key":"e_1_2_8_15_1","first-page":"877","article-title":"Receptor binding, analgesic and antitussive potency of tramadol and other selected opioids","volume":"38","author":"Hennies H\u2010H","year":"1988","journal-title":"Arzneimittelforschung"},{"key":"e_1_2_8_16_1","first-page":"285","volume-title":"Ionic Channels of Excitable Membranes","author":"Hille B","year":"1984"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2003.01514.x"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000539-199610000-00021"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(77)90308-9"},{"key":"e_1_2_8_20_1","first-page":"681","article-title":"Tramadol \u2013 the impact of its pharmacokinetic and pharmacodynamic properties on the clinical management of pain","volume":"53","author":"Klotz U","year":"2003","journal-title":"Arzneimittelforschung"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(93)90568-6"},{"issue":"1","key":"e_1_2_8_22_1","first-page":"S190","article-title":"Effect of tramadol metabolite M1 on glutamatergic excitatory transmission in rat spinal dorsal horn neurons","volume":"55","author":"Koga A","year":"2006","journal-title":"Neurosci Res"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0706225"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001503-200008000-00010"},{"key":"e_1_2_8_25_1","first-page":"1932","article-title":"Metabolismus von Tramadol bei Mensch und Tier","volume":"31","author":"Lintz W","year":"1981","journal-title":"Arzneimittelforschung"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-200060050-00007"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1159\/000072358"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(02)01368-7"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1097\/00115550-199823060-00012"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.medengphy.2004.02.009"},{"key":"e_1_2_8_31_1","first-page":"275","article-title":"Opioid and nonopioid components independently contribute to the mechanism of action of tramadol, an \u2018atypical\u2019 opioid analgesic","volume":"260","author":"Raffa RB","year":"1992","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/aef163"},{"key":"e_1_2_8_33_1","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/S0022-3565(24)29325-3","article-title":"Inhibition by tramadol of muscarinic receptor\u2010induced responses in cultured adrenal medullary cells and in Xenopus laevis oocytes expressing cloned M1 receptors","volume":"299","author":"Shiraishi M","year":"2001","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0704703"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1139\/y74-071"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpain.2005.09.001"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000539-200106000-00040"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-199911000-00042"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1745-7254.2006.00274.x"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.bjp.0706868","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.bjp.0706868","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1038\/sj.bjp.0706868","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T17:47:14Z","timestamp":1736531234000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1038\/sj.bjp.0706868"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,10]]},"references-count":38,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2006,10]]}},"alternative-id":["10.1038\/sj.bjp.0706868"],"URL":"https:\/\/doi.org\/10.1038\/sj.bjp.0706868","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,10]]},"assertion":[{"value":"2009-01-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}