{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T08:32:19Z","timestamp":1771057939903,"version":"3.50.1"},"reference-count":57,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2013,4,8]],"date-time":"2013-04-08T00:00:00Z","timestamp":1365379200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2013,5]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Antagonism of both <jats:styled-content style=\"fixed-case\">NK<jats:sub>1<\/jats:sub><\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">NK<jats:sub>3<\/jats:sub><\/jats:styled-content> receptors may be an effective strategy in the pharmacotherapy of schizophrenia, drug addiction or depression. <jats:styled-content style=\"fixed-case\">GSK<\/jats:styled-content>1144814 is a novel selective dual <jats:styled-content style=\"fixed-case\">NK<jats:sub>1<\/jats:sub>\/NK<jats:sub>3<\/jats:sub><\/jats:styled-content> receptor antagonist. The potential influence of GSK1144814 on the effects of alcohol was investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In a blinded, randomized, placebo\u2010controlled, two period crossover study, the pharmacokinetics and central nervous system (<jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content>) effects of single oral doses of 200\u2009mg <jats:styled-content style=\"fixed-case\">GSK<\/jats:styled-content>1144814 were evaluated in 20 healthy volunteers, using a controlled alcohol infusion paradigm to maintain stable alcohol concentrations with subsequent analysis of eye movements, adaptive tracking, body sway, visual analogue scales, Epworth sleepiness scale and the verbal visual learning test.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Frequent adverse effects were mild somnolence, fatigue and headache. Plasma concentration of <jats:styled-content style=\"fixed-case\">GSK<\/jats:styled-content>1144814 in the presence of alcohol was maximal 1.5 h after dose administration. <jats:styled-content style=\"fixed-case\">GSK<\/jats:styled-content>1144814 did not affect alcohol pharmacokinetics. Co\u2010administration of <jats:styled-content style=\"fixed-case\">GSK<\/jats:styled-content>1144814 and alcohol impaired saccadic reaction time and peak velocity, adaptive tracking, alertness, sleepiness, word recognition and recognition reaction time compared with administration of alcohol alone, but the size of the interaction was small.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Administration of <jats:styled-content style=\"fixed-case\">GSK<\/jats:styled-content>1144814 in the presence of alcohol was generally well tolerated and not likely to produce clinically relevant additional impairments after alcohol consumption.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.12004","type":"journal-article","created":{"date-parts":[[2012,10,15]],"date-time":"2012-10-15T17:08:34Z","timestamp":1350320914000},"page":"1328-1339","source":"Crossref","is-referenced-by-count":12,"title":["Pharmacokinetics and central nervous system effects of the novel dual <scp>NK<sub>1<\/sub>\/NK<sub>3<\/sub><\/scp> receptor antagonist <scp>GSK<\/scp>1144814 in alcohol\u2010intoxicated volunteers"],"prefix":"10.1111","volume":"75","author":[{"given":"Erik T.","family":"te Beek","sequence":"first","affiliation":[{"name":"Centre for Human Drug Research  Leiden the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justin L.","family":"Hay","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research  Leiden the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan N.","family":"Bullman","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline Research &amp; Development Limited  Harlow UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clare","family":"Burgess","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline Research &amp; Development Limited  Harlow UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kimberly J.","family":"Nahon","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research  Leiden the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erica S.","family":"Klaassen","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research  Leiden the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank A.","family":"Gray","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline Research &amp; Development Limited  Harlow UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joop M. 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