{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T14:53:12Z","timestamp":1791903192140,"version":"4.3.4"},"reference-count":25,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2012,1,9]],"date-time":"2012-01-09T00:00:00Z","timestamp":1326067200000},"content-version":"vor","delay-in-days":4331,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["European Journal of Pain"],"published-print":{"date-parts":[[2000,3]]},"abstract":"<jats:p>This study aims to assess whether the antinociceptive actions of methadone are mediated solely through opioid mechanisms, or whether its reported affinity for NMDA receptors has physiological relevance <jats:italic>in vivo<\/jats:italic>. Methadone is a \u03bc\u2010opioid receptor agonist reported to relieve pain unresponsive to other opioids. It is a racemic mixture comprising <jats:italic>d<\/jats:italic> \u2010 and <jats:italic>l<\/jats:italic> \u2010optical isomers; the <jats:italic>d<\/jats:italic> \u2010isomer has a lower affinity for opioid receptors, and both also exhibit NMDA receptor binding, likely to indicate antagonist activity. <jats:italic>d<\/jats:italic> \u2010Methadone is antinociceptive in behavioural studies via non\u2010opioid mechanisms, which could include functional NMDA receptor\u2010blocking activity. Here we investigate the ability of<jats:italic>d<\/jats:italic> \u2010 and <jats:italic>dl<\/jats:italic> \u2010methadone to inhibit noxious and innocuous electrically\u2010evoked responses of dorsal horn neurones in the anaesthetized rat.<\/jats:p><jats:p>Racemic methadone (5, 25, 50, 250 \u03bcg) applied spinally, dose\u2010relatedly inhibited the C\u2010fibre evoked response, input and wind\u2010up of the neurones, with a profile resembling that of morphine. d\u2010Methadone (5, 25, 50, 250, 500 \u03bcg) was also inhibitory, although less potent by a factor of between 13 and 48 depending on the neuronal measure; its profile of inhibition resembled that of the racemic mixture rather than an NMDA receptor antagonist. Both compounds had minimal effects on A\u03b2\u2010fibre\u2010evoked activity. The inhibitory effects of both <jats:italic>d<\/jats:italic> \u2010 and <jats:italic>dl<\/jats:italic> \u2010methadone on noxious\u2010evoked activity were naloxone reversible. The naloxone reversibility of <jats:italic>d<\/jats:italic> \u2010methadone inhibitions is best interpreted as indicative of a purely opioid mechanism of action. However, the ability of naloxone to reverse the effects of <jats:italic>d<\/jats:italic> \u2010methadone may also reflect a degree of synergy between weak NMDA antagonist and opioid agonist activity. Copyright 2000 European Federation of Chapters of the International Association for the Study of Pain<\/jats:p>","DOI":"10.1053\/eujp.1999.0147","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T11:23:34Z","timestamp":1027682614000},"page":"19-26","source":"Crossref","is-referenced-by-count":30,"title":["Neuronal inhibitory effects of methadone are predominantly opioid receptor mediated in the rat spinal cord <i>in vivo<\/i>"],"prefix":"10.1002","volume":"4","author":[{"given":"Katherine J.","family":"Carpenter","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Chapman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony H.","family":"Dickenson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,1,9]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(96)03123-5"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(95)01023-O"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(92)90780-D"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19931001)72:7<2266::AID-CNCR2820720734>3.0.CO;2-P"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-6147(90)90228-Z"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0028-3908(91)90027-9"},{"key":"e_1_2_1_8_1","first-page":"525","volume-title":"Proceedings of the 7th World Congress on Pain Research and Management","author":"Dickenson A. 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