{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T23:43:18Z","timestamp":1790034198683,"version":"4.0.1"},"reference-count":87,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,11,14]],"date-time":"2018-11-14T00:00:00Z","timestamp":1542153600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Medicinal Research Reviews"],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Narcolepsy is a rare, chronic neurological disease characterized by excessive daytime sleepiness, cataplexy, vivid hallucinations, and sleep paralysis. Narcolepsy occurs in approximately 1 of 3000 people, affecting mainly adolescents aged 15 to 30 years. Recently, people with narcolepsy were shown to exhibit extensive orexin\/hypocretin neuronal loss. The orexin system regulates sleep\/wake control via complex interactions with monoaminergic, cholinergic and GABA\u2010ergic neuronal systems. Currently, no cure for narcolepsy exists, but some symptoms can be controlled with medication (eg, stimulants, antidepressants, etc). Orexin supplementation represents a more sophisticated way to treat narcolepsy because it addresses the underlying cause of the disease and not just the symptoms. Research on orexin supplementation in the treatment of sleep disorders has strongly increased over the past two decades. This review focuses on a brief description of narcolepsy, the mechanisms by which the orexin system regulates sleep\/wake cycles, and finally, possible therapeutic options based on orexin supplementation in animal models and patients with narcolepsy.<\/jats:p>","DOI":"10.1002\/med.21550","type":"journal-article","created":{"date-parts":[[2018,11,14]],"date-time":"2018-11-14T04:05:48Z","timestamp":1542168348000},"page":"961-975","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Orexin supplementation in narcolepsy treatment: A review"],"prefix":"10.1002","volume":"39","author":[{"given":"Eugenie","family":"Nepovimova","sequence":"first","affiliation":[{"name":"Department of Chemistry Faculty of Science, University of Hradec Kralove Hradec Kralove Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana","family":"Janockova","sequence":"additional","affiliation":[{"name":"Biomedical Research Centre, University Hospital Hradec Kralove Hradec Kralove Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Misik","sequence":"additional","affiliation":[{"name":"Biomedical Research Centre, University Hospital Hradec Kralove Hradec Kralove Czech Republic"},{"name":"Department of Toxicology and Military Pharmacy Faculty of Military Health Sciences, University of Defence Hradec Kralove Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stepan","family":"Kubik","sequence":"additional","affiliation":[{"name":"Institute of Physiology, Academy of Sciences of the Czech Republic Prague 4 Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ales","family":"Stuchlik","sequence":"additional","affiliation":[{"name":"Institute of Physiology, Academy of Sciences of the Czech Republic Prague 4 Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karel","family":"Vales","sequence":"additional","affiliation":[{"name":"Institute of Physiology, Academy of Sciences of the Czech Republic Prague 4 Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Korabecny","sequence":"additional","affiliation":[{"name":"Biomedical Research Centre, University Hospital Hradec Kralove Hradec Kralove Czech Republic"},{"name":"Department of Toxicology and Military Pharmacy Faculty of Military Health Sciences, University of Defence Hradec Kralove Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Mezeiova","sequence":"additional","affiliation":[{"name":"Biomedical Research Centre, University Hospital Hradec Kralove Hradec Kralove Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Dolezal","sequence":"additional","affiliation":[{"name":"Department of Chemistry Faculty of Science, University of Hradec Kralove Hradec Kralove Czech Republic"},{"name":"Biomedical Research Centre, University Hospital Hradec Kralove Hradec Kralove Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ondrej","family":"Soukup","sequence":"additional","affiliation":[{"name":"Biomedical Research Centre, University Hospital Hradec Kralove Hradec Kralove Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tereza","family":"Kobrlova","sequence":"additional","affiliation":[{"name":"Biomedical Research Centre, University Hospital Hradec Kralove Hradec Kralove Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ngoc Lam","family":"Pham","sequence":"additional","affiliation":[{"name":"Department of Chemistry Faculty of Science, University of Hradec Kralove Hradec Kralove Czech Republic"},{"name":"Biomedical Research Centre, University Hospital Hradec Kralove Hradec Kralove Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thuy Duong","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Chemistry Faculty of Science, University of Hradec Kralove Hradec Kralove Czech Republic"},{"name":"Biomedical Research Centre, University Hospital Hradec Kralove Hradec Kralove Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Konecny","sequence":"additional","affiliation":[{"name":"Biomedical Research Centre, University Hospital Hradec Kralove Hradec Kralove Czech Republic"},{"name":"Department of Toxicology and Military Pharmacy Faculty of Military Health Sciences, University of Defence Hradec Kralove Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9664-1109","authenticated-orcid":false,"given":"Kamil","family":"Kuca","sequence":"additional","affiliation":[{"name":"Department of Chemistry Faculty of Science, University of Hradec Kralove Hradec Kralove Czech Republic"},{"name":"Biomedical Research Centre, University Hospital Hradec Kralove Hradec Kralove Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,11,14]]},"reference":[{"key":"e_1_2_9_1_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2006.07.011"},{"key":"e_1_2_9_1_3_1","unstructured":"National Institute of Neurological Disorders and Stroke.Narcolepsy fact sheet.https:\/\/www.ninds.nih.gov\/Disorders\/Patient\u2010Caregiver\u2010Education\/Fact\u2010Sheets\/Narcolepsy\u2010Fact\u2010Sheet. Accessed 5 September 2018."},{"key":"e_1_2_9_1_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/practneurol-2014-000837"},{"key":"e_1_2_9_1_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1500587"},{"key":"e_1_2_9_1_6_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.14-0970"},{"key":"e_1_2_9_1_7_1","first-page":"190","article-title":"Etiopathogenesis and neurobiology of narcolepsy: a review","volume":"8","author":"Kumar S","year":"2014","journal-title":"J Clin Diagn Res"},{"key":"e_1_2_9_1_8_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.50.2_Suppl_1.S16"},{"key":"e_1_2_9_1_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2006.05.006"},{"key":"e_1_2_9_1_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.1.322"},{"key":"e_1_2_9_1_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(00)01594-0"},{"key":"e_1_2_9_1_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80949-6"},{"key":"e_1_2_9_1_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0163-7258(02)00171-7"},{"key":"e_1_2_9_1_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2013.07.025"},{"key":"e_1_2_9_1_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(01)01839-0"},{"key":"e_1_2_9_1_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)00058-1"},{"key":"e_1_2_9_1_17_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2005-0296"},{"key":"e_1_2_9_1_18_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-23-09996.1998"},{"key":"e_1_2_9_1_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-394623-2.00004-4"},{"key":"e_1_2_9_1_20_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pharmtox-010510-100528"},{"key":"e_1_2_9_1_21_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.2.748"},{"key":"e_1_2_9_1_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(05)70196-4"},{"key":"e_1_2_9_1_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(00)02002-6"},{"key":"e_1_2_9_1_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-017-0865-z"},{"key":"e_1_2_9_1_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2018.00095"},{"key":"e_1_2_9_1_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2017.00357"},{"key":"e_1_2_9_1_27_1","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/S0022-3565(24)38126-1","article-title":"Orexin A but not orexin B rapidly enters brain from blood by simple diffusion","volume":"289","author":"Kastin AJ","year":"1999","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_9_1_28_1","first-page":"23","article-title":"Systemic administration of hypocretin\u20101 reduces cataplexy and normalizes sleep and waking durations in narcoleptic dogs","volume":"3","author":"John J","year":"2000","journal-title":"Sleep Res. Online"},{"key":"e_1_2_9_1_29_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.2001.85.5.2008"},{"key":"e_1_2_9_1_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(98)00600-9"},{"key":"e_1_2_9_1_31_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.08-12-04790.1988"},{"key":"e_1_2_9_1_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/26.8.953"},{"key":"e_1_2_9_1_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0196-9781(02)00109-2"},{"key":"e_1_2_9_1_34_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.19.10911"},{"key":"e_1_2_9_1_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(99)01824-7"},{"key":"e_1_2_9_1_36_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0400590101"},{"key":"e_1_2_9_1_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.21604"},{"key":"e_1_2_9_1_38_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3878-07.2007"},{"key":"e_1_2_9_1_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(99)05582-8"},{"key":"e_1_2_9_1_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/79690"},{"key":"e_1_2_9_1_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2010.12.005"},{"key":"e_1_2_9_1_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(02)00089-1"},{"key":"e_1_2_9_1_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81965-0"},{"key":"e_1_2_9_1_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81973-X"},{"key":"e_1_2_9_1_45_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0018697"},{"key":"e_1_2_9_1_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(01)00293-8"},{"key":"e_1_2_9_1_47_1","doi-asserted-by":"publisher","DOI":"10.5665\/sleep.2870"},{"key":"e_1_2_9_1_48_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0073-14.2014"},{"key":"e_1_2_9_1_49_1","doi-asserted-by":"publisher","DOI":"10.5665\/sleep.2296"},{"key":"e_1_2_9_1_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.13158"},{"key":"e_1_2_9_1_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2008.06446.x"},{"key":"e_1_2_9_1_52_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.6069-10.2011"},{"key":"e_1_2_9_1_53_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI71017"},{"key":"e_1_2_9_1_54_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5632-12.2013"},{"key":"e_1_2_9_1_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2017.03.017"},{"key":"e_1_2_9_1_56_1","doi-asserted-by":"publisher","DOI":"10.1385\/MN:29:1:41"},{"key":"e_1_2_9_1_57_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0953-816X.2004.03366.x"},{"key":"e_1_2_9_1_58_1","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/27.8.1465"},{"key":"e_1_2_9_1_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2006.05.017"},{"key":"e_1_2_9_1_60_1","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.2002.7888"},{"key":"e_1_2_9_1_61_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.240450307"},{"key":"e_1_2_9_1_62_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0095342"},{"key":"e_1_2_9_1_63_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1700499114"},{"key":"e_1_2_9_1_64_1","doi-asserted-by":"publisher","DOI":"10.1080\/13543784.2018.1459561"},{"key":"e_1_2_9_1_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2008.10.010"},{"key":"e_1_2_9_1_66_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.1130"},{"key":"e_1_2_9_1_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sleep.2007.03.008"},{"key":"e_1_2_9_1_68_1","doi-asserted-by":"publisher","DOI":"10.5665\/sleep.2080"},{"key":"e_1_2_9_1_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2015.05.012"},{"issue":"922","key":"e_1_2_9_1_70_1","first-page":"1","article-title":"Pharmacokinetic studies with BLX\u20101026, a novel orexin\u20102 receptor agonist with anti\u2010obesity property, in rats","volume":"22","author":"Sen A","year":"2008","journal-title":"FASEB J"},{"issue":"920","key":"e_1_2_9_1_71_1","first-page":"2","article-title":"In\u2010vitro metabolism studies with BLX\u20101026, a novel orexin\u20102 agonist with anti\u2010obesity activity","volume":"22","author":"Mukherjee A","year":"2008","journal-title":"FASEB JournalI"},{"key":"e_1_2_9_1_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-894X(02)00851-X"},{"key":"e_1_2_9_1_73_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5b00988"},{"key":"e_1_2_9_1_74_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.6b00029"},{"key":"e_1_2_9_1_75_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5b01394"},{"key":"e_1_2_9_1_76_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1012456108"},{"key":"e_1_2_9_1_77_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0073-14.2014"},{"key":"e_1_2_9_1_78_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.6b00333"},{"key":"e_1_2_9_1_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2004.10.005"},{"key":"e_1_2_9_1_80_1","doi-asserted-by":"publisher","DOI":"10.1080\/10401230490453743"},{"key":"e_1_2_9_1_81_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.105.099010"},{"key":"e_1_2_9_1_82_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI32829"},{"key":"e_1_2_9_1_83_1","article-title":"Discovery of an orexin receptor positive potentiator","volume":"1","author":"Lee J","year":"2010","journal-title":"Chem Sci R Soc Chem"},{"key":"e_1_2_9_1_84_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1584307"},{"key":"e_1_2_9_1_85_1","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/30.12.1705"},{"key":"e_1_2_9_1_86_1","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/25.8.42"},{"key":"e_1_2_9_1_87_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-012-0150-9"},{"key":"e_1_2_9_1_88_1","first-page":"CD003724","article-title":"Antidepressant drugs for narcolepsy","volume":"3","author":"Vignatelli L","year":"2005","journal-title":"Cochrane Database Syst Rev"}],"container-title":["Medicinal Research Reviews"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmed.21550","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/med.21550","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/med.21550","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/med.21550","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T01:51:05Z","timestamp":1775267465000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/med.21550"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,14]]},"references-count":87,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2019,5]]}},"alternative-id":["10.1002\/med.21550"],"URL":"https:\/\/doi.org\/10.1002\/med.21550","archive":["Portico"],"relation":{},"ISSN":["0198-6325","1098-1128"],"issn-type":[{"value":"0198-6325","type":"print"},{"value":"1098-1128","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,11,14]]},"assertion":[{"value":"2018-06-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-10-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-11-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}