{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T16:49:05Z","timestamp":1777222145184,"version":"3.51.4"},"reference-count":32,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2009,2,3]],"date-time":"2009-02-03T00:00:00Z","timestamp":1233619200000},"content-version":"vor","delay-in-days":3778,"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":[[1998,10]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>In order to resolve the extent to which presynaptic noradrenergic mechanisms contribute to the anaesthetic\u2010sparing effects of \u03b1<jats:sub>2<\/jats:sub>\u2010adrenoceptor agonists <jats:italic>in vivo<\/jats:italic> microdialysis was used to investigate the combined effects of sodium pentobarbitone and imidazol(in)e \u03b1<jats:sub>2<\/jats:sub>\u2010adrenoceptor agonists on extracellular levels of noradrenaline (NA) in the rat frontal cortex.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Dialysate levels of NA were markedly reduced by the addition of TTX (2\u2003\u03bc<jats:sc>M<\/jats:sc>) or by the removal of calcium in the perfusate. These data imply that dialysate NA levels are ultimately dependent on exocytotic release mechanisms from afferent coeruleo\u2010cortical neurones.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Systemic administration of sodium pentobarbitone (85\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>, i.p.) induced general anaesthesia and reduced NA levels by 92% after 30\u2003min. The restoration of basal levels 90\u2003min later was closely associated with a return of the corneal blink reflex.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Basal NA levels in conscious animals were not affected by an intravenous infusion of equally radioactive solutions of either imidazoline (clonidine) or imidazole (mivazerol) \u03b1<jats:sub>2<\/jats:sub>\u2010adrenoceptor agonists. The dose rate employed for each compound was 2\u2003\u03bcg\u2003kg<jats:sup>\u22121<\/jats:sup>\u2003h<jats:sup>\u22121<\/jats:sup> over 2\u2003h.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The co\u2010administration of intravenous clonidine or mivazerol, each at 2\u2003\u03bcg\u2003kg<jats:sup>\u22121<\/jats:sup>\u2003h<jats:sup>\u22121<\/jats:sup> for 2\u2003h, with sodium pentobarbitone (85\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>, i.p.), produced a marked and prolonged reduction in NA efflux. After 2\u2003h, NA levels remained suppressed by 95% (clonidine) and 80% (mivazerol) and animals remained deeply anaesthetized.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The accumulation of tritium in brain tissue was 42\u201373% lower across all brain regions examined after [<jats:sup>3<\/jats:sup>H]\u2010mivazerol administration than after [<jats:sup>3<\/jats:sup>H]\u2010clonidine administration. Sodium pentobarbitone did not alter the accumulation of tritium in brain tissue after the administration of either \u03b1<jats:sub>2<\/jats:sub>\u2010adrenoceptor agonist.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These data demonstrate that \u03b1<jats:sub>2<\/jats:sub>\u2010adrenoceptor agonists potentiate the inhibitory effects of sodium pentobarbitone on extracellular levels of NA in the frontal cortex. Further studies will be necessary to establish a causal role of noradrenergic mechanisms in the potentiation of anaesthesia by selective \u03b1<jats:sub>2<\/jats:sub>\u2010adrenoceptor agonists.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (1998) <jats:bold>125<\/jats:bold>, 441\u2013446; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0702091\">10.1038\/sj.bjp.0702091<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0702091","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T19:25:27Z","timestamp":1106940327000},"page":"441-446","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Potentiation of barbiturate\u2010induced alterations in presynaptic noradrenergic function in rat frontal cortex by imidazol(in)e <i>\u03b1<\/i><sub>2<\/sub>\u2010adrenoceptor agonists"],"prefix":"10.1111","volume":"125","author":[{"given":"J W","family":"Dalley","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C A","family":"Parker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E","family":"W\u00fclfert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A L","family":"Hudson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D J","family":"Nutt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,2,3]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"369","article-title":"Barbiturate inhibition of calcium uptake by depolarised nerve terminals in vitro","volume":"11","author":"Blaustein M.P.","year":"1975","journal-title":"Mol. 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