{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T11:48:59Z","timestamp":1789818539712,"version":"4.0.1"},"reference-count":25,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2009,1,30]],"date-time":"2009-01-30T00:00:00Z","timestamp":1233273600000},"content-version":"vor","delay-in-days":2162,"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":[[2003,3]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Although the principal pharmacological targets of local anaesthetics (LAs) are voltage\u2010gated Na<jats:sup>+<\/jats:sup> channels, other targets have also been suggested. Here we examined the effects of LAs on the N\u2010methyl\u2010D\u2010aspartate (NMDA) receptor, a receptor involved in the process of nociception.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>LAs (bupivacaine, lidocaine, procaine, and tetracaine) reversibly and concentration\u2010dependently inhibited recombinant \u03b51\/\u03b61 and \u03b52\/\u03b61 NMDA receptors expressed in <jats:italic>Xenopus<\/jats:italic> oocytes (IC<jats:sub>50<\/jats:sub>s for bupivacaine, lidocaine, procaine, and tetracaine were 1032.0, 1174.1, 642.1 and 653.8 \u03bc<jats:sc>M<\/jats:sc> at the \u03b51\/\u03b61 receptor; and 1090.8, 1821.3, 683.0 and 662.5 \u03bc<jats:sc>M<\/jats:sc> respectively (at the \u03b52\/\u03b61 receptor). Bupivacaine and procaine were non\u2010competitive antagonists; bupivacaine possesses non\u2010competitive and competitive actions when interacting with glycine, whereas procaine has only non\u2010competitive action.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Mutation of asparagine residue at position 598 (Asp<jats:sup>598<\/jats:sup>) in the \u03b61 subunit, a residue associated with the blockade site for Mg<jats:sup>2+<\/jats:sup> and ketamine, to glutamine or arginine reduced the sensitivity to procaine but not to bupivacaine. Thus, procaine may interact with sites of action that are closely related to those of Mg<jats:sup>2+<\/jats:sup> and ketamine blockade.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These results suggest that LAs inhibit the NMDA receptor by various mechanisms.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2003) <jats:bold>138<\/jats:bold>, 876\u2013882. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0705107\">10.1038\/sj.bjp.0705107<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0705107","type":"journal-article","created":{"date-parts":[[2003,3,17]],"date-time":"2003-03-17T18:23:15Z","timestamp":1047925395000},"page":"876-882","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":86,"title":["Local anaesthetics have different mechanisms and sites of action at the recombinant N\u2010methyl\u2010D\u2010aspartate (NMDA) receptors"],"prefix":"10.1111","volume":"138","author":[{"given":"Masahiro","family":"Sugimoto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ichiro","family":"Uchida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Mashimo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1,30]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"491","volume-title":"Anesthesia","author":"BERDE C.B.","year":"1999"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.140.3565.392"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-196809000-00028"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0702164"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-195401000-00001"},{"key":"e_1_2_7_7_1","first-page":"7","article-title":"The glutamate receptor ion channels","volume":"51","author":"DINGLEDINE R.","year":"1999","journal-title":"Pharmacol. 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