{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T16:30:56Z","timestamp":1759336256325,"version":"3.41.0"},"reference-count":93,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2016,3,15]],"date-time":"2016-03-15T00:00:00Z","timestamp":1458000000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Synapse"],"published-print":{"date-parts":[[2016,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Brain bioavailability of drugs developed to address central nervous system diseases is classically documented through cerebrospinal fluid collected in normal animals, i.e., through an approximation as there are fundamental differences between cerebrospinal fluid and tissue contents. The fact that disease might affect brain availability of drugs is almost never considered at this stage although several conditions are associated with blood\u2013brain barrier damage. Building upon our expertise in Parkinson's disease translational research, the present study addressed this gap comparing plasma and cerebrospinal fluid bioavailability of<jats:sc>l<\/jats:sc>\u22123,4\u2010dihydroxyphenylalanine, carbamazepine, quinidine, lovastatin, and simvastatin, in healthy and 1\u2010methyl\u20104\u2010phenyl\u20101,2,3,6\u2010tetrahydropyridine\u2010treated macaques, the gold standard model of Parkinson's disease. The drugs were selected based upon their differential transport across the blood\u2013brain barrier. Interestingly, brain bioavailability of quinidine was decreased while others were unaffected. Pharmacokinetics and pharmacodynamics experiments of drugs addressing Parkinson's disease might thus be performed in healthy animals unless the drugs are known to interact with the organic cation transporter.<jats:bold>Synapse 70:231\u2013239, 2016<\/jats:bold>. \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/syn.21889","type":"journal-article","created":{"date-parts":[[2016,1,22]],"date-time":"2016-01-22T13:51:38Z","timestamp":1453470698000},"page":"231-239","source":"Crossref","is-referenced-by-count":11,"title":["Permeability of blood\u2013brain barrier in macaque model of 1\u2010methyl\u20104\u2010phenyl\u20101,2,3,6\u2010tetrahydropyridine\u2010induced Parkinson disease"],"prefix":"10.1002","volume":"70","author":[{"given":"Thibaud","family":"Thiollier","sequence":"first","affiliation":[{"name":"Cynbiose Marcy l'Etoile France"},{"name":"Univ. de Bordeaux, Institut des Maladies Neurod\u00e9g\u00e9n\u00e9ratives, UMR 5293 33000 Bordeaux France"},{"name":"CNRS, Institut des Maladies Neurod\u00e9g\u00e9n\u00e9ratives, UMR 5293 33000 Bordeaux France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caisheng","family":"Wu","sequence":"additional","affiliation":[{"name":"Institute of Materia Medica, Chinese Academy of Medical Sciences Beijing People's Republic of China 100050"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hugues","family":"Contamin","sequence":"additional","affiliation":[{"name":"Cynbiose Marcy l'Etoile France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qin","family":"Li","sequence":"additional","affiliation":[{"name":"Motac Neuroscience Manchester United Kingdom"},{"name":"Institute of Laboratory Animal Sciences, China Academy of Medical Sciences Beijing People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinlan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Materia Medica, Chinese Academy of Medical Sciences Beijing People's Republic of China 100050"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erwan","family":"Bezard","sequence":"additional","affiliation":[{"name":"Univ. de Bordeaux, Institut des Maladies Neurod\u00e9g\u00e9n\u00e9ratives, UMR 5293 33000 Bordeaux France"},{"name":"CNRS, Institut des Maladies Neurod\u00e9g\u00e9n\u00e9ratives, UMR 5293 33000 Bordeaux France"},{"name":"Institute of Laboratory Animal Sciences, China Academy of Medical Sciences Beijing People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,3,15]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdd.2510040210"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3000664"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.44.8.1491"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000147965.52712.fa"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awr298"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2009.05.018"},{"key":"e_1_2_5_8_1","first-page":"148","article-title":"Cerebral subarachnoid sampling of cerebrospinal fluid in the rhesus monkey","volume":"44","author":"Bacher JD","year":"1994","journal-title":"Lab Anim Sci"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1211\/jpp.58.1.0008"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-004-0256-2"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2009.04.005"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/35086062"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-17-06853.2001"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2006.02.003"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2004.10.005"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2590-10.2010"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/00002826-199106000-00010"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.105.004424"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.2217\/1745509X.4.1.47"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.107.125666"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2005.04281.x"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2982.2008.01226.x"},{"key":"e_1_2_5_23_1","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/S0090-9556(24)15144-6","article-title":"Pharmacological Inhibition of P\u2010glycoprotein transport enhances the distribution of HIV\u20101 protease inhibitors into brain and testes","volume":"28","author":"Choo EF","year":"2000","journal-title":"Drug Metab Dispos"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0694-180"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1517\/17460441.3.6.677"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.104.001230"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1997.03550160069041"},{"key":"e_1_2_5_28_1","doi-asserted-by":"crossref","unstructured":"FasanoS BezardE D'AntoniA FrancardoV IndrigoM QinL et al.2010.Inhibition of Ras\u2010guanine nucleotide\u2010releasing factor 1 (Ras\u2010GRF1) signaling in the striatum reverts motor symptoms associated withl\u2010dopa\u2010induced dyskinesia.PNAS2010.http:\/\/www.pnas.org\/content\/early\/2010\/11\/24\/1012071107","DOI":"10.1073\/pnas.1012071107"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(99)00641-8"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0014053"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410340415"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410270507"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.57.2.4"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.60.8.1119"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0582-08.2008"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2009.01.079"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.50.2.318"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2012.06.012"},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.1211\/146080899128734820"},{"key":"e_1_2_5_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdd.325"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2012.03701.x"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1006481423298"},{"key":"e_1_2_5_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20369"},{"key":"e_1_2_5_44_1","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1016\/S0022-3565(24)37075-2","article-title":"P\u2010Glycoprotein mediates the efflux of quinidine across the blood\u2013brain barrier","volume":"283","author":"Kusuhara H","year":"1997","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_5_45_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.326.7404.1423"},{"key":"e_1_2_5_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2010.06801.x"},{"key":"e_1_2_5_47_1","doi-asserted-by":"publisher","DOI":"10.2174\/138920008783331077"},{"key":"e_1_2_5_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1974.tb04013.x"},{"key":"e_1_2_5_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2008.08.032"},{"key":"e_1_2_5_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0270(00)00283-1"},{"key":"e_1_2_5_51_1","doi-asserted-by":"crossref","first-page":"4245","DOI":"10.1073\/pnas.82.12.4245","article-title":"Amyloid plaque core protein in Alzheimer disease and Down syndrome","volume":"82","author":"Masters CL","journal-title":"PNAS"},{"key":"e_1_2_5_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.2600700516"},{"key":"e_1_2_5_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3430"},{"key":"e_1_2_5_54_1","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/S0022-3565(24)29357-5","article-title":"Comparison of \u00ab type I \u00bb and \u00ab type II \u00bb organic cation transport by organic cation transporters and organic anion\u2010transporting polypeptides","volume":"298","author":"Montfoort JE","year":"2001","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_5_55_1","doi-asserted-by":"crossref","first-page":"1946","DOI":"10.1126\/science.286.5446.1946","article-title":"Stimulation of bone formation in vitro and in rodents by statins","volume":"286","author":"Mundy G","journal-title":"Science"},{"key":"e_1_2_5_56_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awn235"},{"key":"e_1_2_5_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2012.221"},{"key":"e_1_2_5_58_1","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1016\/S0022-3565(24)35167-5","article-title":"Na+\u2010dependent carnitine transport by organic cation transporter (OCTN2): Its pharmacological and toxicological relevance","volume":"291","author":"Ohashi R","year":"1999","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_5_59_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awr165"},{"key":"e_1_2_5_60_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2125.2001.01359.x"},{"key":"e_1_2_5_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2006.10.013"},{"key":"e_1_2_5_62_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198505163122001"},{"key":"e_1_2_5_63_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-9-188"},{"key":"e_1_2_5_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2009.02.321"},{"key":"e_1_2_5_65_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI59426"},{"key":"e_1_2_5_66_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-200111160-00037"},{"issue":"2","key":"e_1_2_5_67_1","first-page":"II51","article-title":"The pharmacological therapeutic management of levodopa\u2010induced dyskinesias in patients with Parkinson's disease","volume":"247","author":"Rascol O.","year":"2000","journal-title":"J Neurol"},{"key":"e_1_2_5_68_1","doi-asserted-by":"publisher","DOI":"10.2174\/138920006775541525"},{"key":"e_1_2_5_69_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbdv.200900103"},{"key":"e_1_2_5_70_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1018975928974"},{"key":"e_1_2_5_71_1","doi-asserted-by":"publisher","DOI":"10.1080\/105172399242799"},{"key":"e_1_2_5_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2006.08.026"},{"key":"e_1_2_5_73_1","doi-asserted-by":"publisher","DOI":"10.1038\/22124"},{"key":"e_1_2_5_74_1","doi-asserted-by":"publisher","DOI":"10.3727\/095535491820873371"},{"key":"e_1_2_5_75_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2003.01686.x"},{"key":"e_1_2_5_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2004.07.011"},{"key":"e_1_2_5_77_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.33.11.1487"},{"key":"e_1_2_5_78_1","doi-asserted-by":"publisher","DOI":"10.1038\/77060"},{"key":"e_1_2_5_79_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00195938"},{"key":"e_1_2_5_80_1","doi-asserted-by":"crossref","first-page":"1845","DOI":"10.2460\/ajvr.1993.54.11.1845","article-title":"Effects of sex, age, puncture site, and blood contamination on the clinical chemistry of cerebrospinal fluid in rhesus macaques (Macaca mulatta)","volume":"54","author":"Smith MO","year":"1993","journal-title":"Am J Vet Res"},{"key":"e_1_2_5_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2571(96)00021-0"},{"key":"e_1_2_5_82_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1745-7254.2006.00246.x"},{"key":"e_1_2_5_83_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-011-9318-1"},{"key":"e_1_2_5_84_1","article-title":"Simvastatin decreases levodopa\u2010induced dyskinesia in monkeys, but not in a randomized, placebo\u2010controlled, multiple cross\u2010over (\u00ab n\u2010of\u20101 \u00bb) exploratory trial of simvastatin against levodopa\u2010induced dyskinesia in Parkinson's disease patients","author":"Tison F","year":"2012","journal-title":"Parkinsonism Relat Disord."},{"key":"e_1_2_5_85_1","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1016\/S0022-3565(25)39496-6","article-title":"Transport mechanism of 3\u2010hydroxy\u20103\u2010methylglutaryl coenzyme A reductase inhibitors at the blood\u2013brain barrier","volume":"267","author":"Tsuji A","year":"1993","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_5_86_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(95)00549-8"},{"key":"e_1_2_5_87_1","first-page":"S203","article-title":"Comprehensive pathological analysis in MPTP\u2010treated macaques reveal widespread synucleopathy and tauopathy","volume":"25","author":"Vital A","year":"2010","journal-title":"Mov Disord"},{"key":"e_1_2_5_88_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2012.03702.x"},{"key":"e_1_2_5_89_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.wnr.0000215769.71657.65"},{"key":"e_1_2_5_90_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0703337"},{"key":"e_1_2_5_91_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2008.10.022"},{"key":"e_1_2_5_92_1","doi-asserted-by":"publisher","DOI":"10.1097\/00002826-198706000-00008"},{"key":"e_1_2_5_93_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0944-06.2006"},{"key":"e_1_2_5_94_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2003.08.065"}],"container-title":["Synapse"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fsyn.21889","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/syn.21889","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T06:23:13Z","timestamp":1748758993000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/syn.21889"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,3,15]]},"references-count":93,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2016,6]]}},"alternative-id":["10.1002\/syn.21889"],"URL":"https:\/\/doi.org\/10.1002\/syn.21889","archive":["Portico"],"relation":{},"ISSN":["0887-4476","1098-2396"],"issn-type":[{"type":"print","value":"0887-4476"},{"type":"electronic","value":"1098-2396"}],"subject":[],"published":{"date-parts":[[2016,3,15]]}}}