{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T22:25:19Z","timestamp":1747779919389},"reference-count":0,"publisher":"Rockefeller University Press","issue":"2","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1995,2,1]]},"abstract":"<jats:p>We have synthesized a model local anesthetic (LA), N-(2-di-N-butyl-aminoethyl)-4-azidobenzamide (DNB-AB), containing the photoactivatable aryl azido moiety, which is known to form a covalent bond to adjacent molecules when exposed to UV light (Fleet, G.W., J.R. Knowles, and R.R. Porter. 1972. Biochemical Journal. 128:499-508. Ji, T.H. 1979. Biochimica et Biophysica Acta. 559:39-69). We studied the effects of DNB-AB on the sodium current (INa) under whole-cell voltage clamp in clonal mammalian GH3 cells and on 3[H]-BTX-B binding to sheep brain synaptoneurosomes. In the absence of UV illumination, DNB-AB behaved similarly to known LAs, producing both reversible block of peak INa (IC50 = 26 microM, 20 degrees C) and reversible inhibition of 3[H]-BTX-B (50 nM in the presence of 0.12 microgram\/liter Leiurus quinquestriatus scorpion venom) binding (IC50 = 3.3 microM, 37 degrees C), implying a noncovalent association between DNB-AB and its receptor(s). After exposure to UV light, both block of INa and inhibition of 3[H]-BTX-B binding were only partially reversible (INa = 42% of control; 3[H]-BTX-B binding = 23% of control) showing evidence of a light-dependent, covalent association between DNB-AB and its receptor(s). In the absence of drug, UV light had less effect on INa (post exposure INa = 96% of control) or on 3[H]-BTX-B binding (post exposure binding = 70% of control). The irreversible block of INa was partially protected by coincubation of DNB-AB with 1 mM bupivacaine (IC50 = 45 microM, for INa inhibition at 20 degrees C, Wang, G.K., and S.Y. Wang. 1992. Journal of General Physiology. 100:1003-1020), (post exposure INa = 73% of control). The irreversible inhibition of 3[H]-BTX-B binding also was partially protected by coincubation with bupivacaine (500 microM, 37 degrees C) (post exposure binding = 51% of control), suggesting that the site of irreversible inhibition of both INa and 3[H]-BTX-B binding is shared with the clinical LA bupivacaine.<\/jats:p>","DOI":"10.1085\/jgp.105.2.267","type":"journal-article","created":{"date-parts":[[2004,5,13]],"date-time":"2004-05-13T23:51:34Z","timestamp":1084492294000},"page":"267-287","update-policy":"http:\/\/dx.doi.org\/10.1085\/jgp.crossmarkpolicy","source":"Crossref","is-referenced-by-count":5,"title":["Irreversible inhibition of sodium current and batrachotoxin binding by a photoaffinity-derivatized local anesthetic."],"prefix":"10.1085","volume":"105","author":[{"given":"J","family":"McHugh","sequence":"first","affiliation":[{"name":"Anesthesia Research Laboratories, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W M","family":"Mok","sequence":"additional","affiliation":[{"name":"Anesthesia Research Laboratories, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G K","family":"Wang","sequence":"additional","affiliation":[{"name":"Anesthesia Research Laboratories, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G","family":"Strichartz","sequence":"additional","affiliation":[{"name":"Anesthesia Research Laboratories, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"291","published-online":{"date-parts":[[1995,2,1]]},"container-title":["The Journal of general physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jgp\/article-pdf\/105\/2\/267\/1768202\/267.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jgp\/article-pdf\/105\/2\/267\/1768202\/267.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,26]],"date-time":"2023-07-26T10:54:50Z","timestamp":1690368890000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jgp\/article\/105\/2\/267\/26429\/Irreversible-inhibition-of-sodium-current-and"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1995,2,1]]},"references-count":0,"journal-issue":{"issue":"2","published-print":{"date-parts":[[1995,2,1]]}},"URL":"https:\/\/doi.org\/10.1085\/jgp.105.2.267","relation":{},"ISSN":["0022-1295","1540-7748"],"issn-type":[{"value":"0022-1295","type":"print"},{"value":"1540-7748","type":"electronic"}],"subject":[],"published":{"date-parts":[[1995,2,1]]}}}