{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T03:48:34Z","timestamp":1773287314081,"version":"3.50.1"},"reference-count":36,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2009,1,30]],"date-time":"2009-01-30T00:00:00Z","timestamp":1233273600000},"content-version":"vor","delay-in-days":3317,"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":[[2000,1]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p><jats:italic>cis<\/jats:italic>\u20109,10\u2010octadecenoamide (\u2018oleamide\u2019) accumulates in CSF on sleep deprivation. It induces sleep in animals (the <jats:italic>trans<\/jats:italic> form is inactive) but its cellular actions are poorly characterized. We have used electrophysiology in cultures from embryonic rat cortex and biochemical studies in mouse nerve preparations to address these issues.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Twenty \u03bc<jats:sc>M<\/jats:sc> <jats:italic>cis<\/jats:italic>\u2010oleamide (but not <jats:italic>trans<\/jats:italic>) reversibly enhanced GABA<jats:sub>A<\/jats:sub> currents and depressed the frequency of spontaneous excitatory and inhibitory synaptic activity in cultured networks.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p><jats:italic>cis<\/jats:italic>\u2010oleamide stereoselectively blocked veratridine\u2010induced (but not K<jats:sup>+<\/jats:sup>\u2010induced) depolarisation of mouse synaptoneurosomes (IC<jats:sub>50<\/jats:sub>, 13.9\u2003\u03bc<jats:sc>M<\/jats:sc>).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The <jats:italic>cis<\/jats:italic> isomer stereoselectively blocked veratridine\u2010induced (but not K<jats:sup>+<\/jats:sup>\u2010induced) [<jats:sup>3<\/jats:sup>H]\u2010GABA release from mouse synaptosomes (IC<jats:sub>50<\/jats:sub>, 4.6\u2003\u03bc<jats:sc>M<\/jats:sc>).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>At 20\u2003\u03bc<jats:sc>M<\/jats:sc> <jats:italic>cis<\/jats:italic>\u2010oleamide, but not <jats:italic>trans<\/jats:italic>, produced a marked inhibition of Na<jats:sup>+<\/jats:sup> channel\u2010dependent rises in intrasynaptosomal Ca<jats:sup>2+<\/jats:sup>.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The physiological significance of these observations was examined by isolating Na<jats:sup>+<\/jats:sup> spikes in cultured pyramidal neurones. Sixty\u2010four \u03bc<jats:sc>M<\/jats:sc> <jats:italic>cis<\/jats:italic>\u2010oleamide did not significantly alter the amplitude, rate of rise or duration of unitary action potentials (1\u2003Hz).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p><jats:italic>cis<\/jats:italic>\u2010Oleamide stereoselectively suppressed sustained repetitive firing (SRF) in these cells with an EC<jats:sub>50<\/jats:sub> of 4.1\u2003\u03bc<jats:sc>M<\/jats:sc> suggesting a frequency\u2010 or state\u2010dependent block of voltage\u2010gated Na<jats:sup>+<\/jats:sup> channels.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Oleamide is a stereoselective modulator of both postsynaptic GABA<jats:sub>A<\/jats:sub> receptors and presynaptic or somatic voltage\u2010gated Na<jats:sup>+<\/jats:sup> channels which are crucial for synaptic inhibition and conduction. The modulatory actions are strikingly similar to those displayed by sedative or anticonvulsant barbiturates and a variety of general anaesthetics.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Oleamide may represent an endogenous modulator for drug receptors and an important regulator of arousal.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2000) <jats:bold>129<\/jats:bold>, 283\u2013290; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0703051\">10.1038\/sj.bjp.0703051<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0703051","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T20:40:58Z","timestamp":1106944858000},"page":"283-290","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Stereoselective modulatory actions of oleamide on GABA<sub>A<\/sub> receptors and voltage\u2010gated Na<sup>+<\/sup> channels <i>in vitro<\/i>: a putative endogenous ligand for depressant drug sites in CNS"],"prefix":"10.1111","volume":"129","author":[{"given":"Bernard","family":"Verdon","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Russell A","family":"Nicholson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C Robin","family":"Ganelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"Lees","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,1,30]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2736(82)90070-0"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199904060-00010"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0920-1211(98)00062-X"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-3278(96)90100-3"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-6147(87)90011-3"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1992.72.suppl_4.S15"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0028-3908(98)00208-1"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0920-1211(92)90065-2"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-6147(96)10015-8"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7770779"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(86)91464-2"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0166-2236(95)80030-6"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/367607a0"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/71.1.15"},{"key":"e_1_2_7_16_1","doi-asserted-by":"crossref","first-page":"3440","DOI":"10.1016\/S0021-9258(19)83641-4","article-title":"A new generation of Ca++ indicators with greatly improved fluorescence properties","volume":"260","author":"GRYNKIEWICZ G.","year":"1985","journal-title":"J. Biol. Chem."},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.139.7.1785"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1006\/abio.1999.4083"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2581319"},{"key":"e_1_2_7_20_1","first-page":"1303","article-title":"Inhibition of voltage\u2010dependent sodium channels by the anticonvulsant \u03b3\u2010aminobutyric acid type A receptor modulator, 3\u2010benzyl\u20103\u2010ethyl\u20102\u2010piperidinone","volume":"285","author":"HILL M.W.","year":"1998","journal-title":"J. Pharm. Exp. Ther."},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.15.8078"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/0041-008X(87)90271-7"},{"key":"e_1_2_7_23_1","first-page":"829","article-title":"Lamotrigine, phenytoin and carbamezepine interactions on the sodium current present in N4TG1 mouse neuroblastoma cells","volume":"266","author":"LANG D.G.","year":"1993","journal-title":"J. Pharm. Exp. Ther."},{"key":"e_1_2_7_24_1","first-page":"861","volume-title":"Lamotrigine mechanisms of action","author":"LEACH M.J.","year":"1995"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/81.4.491"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0701918"},{"key":"e_1_2_7_27_1","first-page":"P190","article-title":"Effects of isoflurane and cis\u20109,10\u2010octadecenoamide (cOA) on the \u03c11 GABA receptor","volume":"509","author":"LEES G.","year":"1998","journal-title":"J. Physiol. (London)"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(93)91660-K"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/PL00005075"},{"key":"e_1_2_7_30_1","first-page":"713","volume-title":"Anticonvulsant drugs: mechanisms of action.","author":"MACDONALD R.L.","year":"1986"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(89)90485-0"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-199605000-00025"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja01174a081"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.16.6192"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-199407000-00016"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4547(19971215)50:6<1047::AID-JNR16>3.0.CO;2-1"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000539-199806000-00031"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.bjp.0703051","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.bjp.0703051","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1038\/sj.bjp.0703051","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,29]],"date-time":"2023-10-29T09:06:32Z","timestamp":1698570392000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1038\/sj.bjp.0703051"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,1]]},"references-count":36,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2000,1]]}},"alternative-id":["10.1038\/sj.bjp.0703051"],"URL":"https:\/\/doi.org\/10.1038\/sj.bjp.0703051","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,1]]},"assertion":[{"value":"2009-01-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}