{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T07:51:45Z","timestamp":1782978705804,"version":"3.54.5"},"reference-count":70,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T00:00:00Z","timestamp":1724284800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Parkinson\u2019s Disease"],"published-print":{"date-parts":[[2024,9,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Noradrenergic signaling declines in Parkinson\u2019s disease (PD) following locus coeruleus neurodegeneration. Epidemiologic studies demonstrate that \u03b2-acting drugs slow PD progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>The primary objective was to compare the safety and effects of 3 \u03b2-adrenoceptor (\u03b2-AR) acting drugs on central nervous system (CNS) function after a single dose in healthy volunteers (HVs) and evaluate the effects of multiple doses of \u03b2-AR acting drugs in HVs and PD-patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>In Part A, HVs received single doses of 32\u200amg salbutamol, 160 \u03bcg clenbuterol, 60\u200amg pindolol and placebo administered in a randomized, 4-way cross-over study. In Part B (randomized cross-over) and Part C (parallel, 2:1 randomized), placebo and\/or clenbuterol (20 \u03bcg on Day 1, 40 \u03bcg on Day 2, 80 \u03bcg on Days 3\u20137) were administered. CNS functions were assessed using the NeuroCart test battery, including pupillometry, adaptive tracking and recall tests.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Twenty-seven HVs and 12 PD-patients completed the study. Clenbuterol improved and pindolol reduced the adaptive tracking and immediate verbal recall performance. Clenbuterol and salbutamol increased and pindolol decreased pupil-to-iris ratios. Clenbuterol was selected for Parts B and C. In Part B, clenbuterol significantly increased performance in adaptive tracking with a tendency toward improved performance in immediate and delayed verbal recall. In Part C trends toward improved performance in immediate and delayed verbal recall were observed in PD-patients. Typical cardiovascular peripheral \u03b2\n                      <jats:sub>2<\/jats:sub>\n                      -AR effects were observed with clenbuterol.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>This study demonstrates the pro-cognitive effects of clenbuterol in HVs with similar trends in PD-patients. The mechanism of action is likely activation of \u03b22-ARs in the CNS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3233\/jpd-240039","type":"journal-article","created":{"date-parts":[[2024,8,27]],"date-time":"2024-08-27T10:09:55Z","timestamp":1724753395000},"page":"1149-1161","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["Cognitive Effects of Three \u03b2-Adrenoceptor Acting Drugs in Healthy Volunteers and Patients with Parkinson\u2019s Disease"],"prefix":"10.1177","volume":"14","author":[{"given":"Pepijn P.N.M.","family":"Eijsvogel","sequence":"first","affiliation":[{"name":"Centre for Human Drug Research, Leiden, The Netherlands"},{"name":"Leiden University Medical Centre, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura G.J.M.","family":"Borghans","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Prins","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research, Leiden, The Netherlands"},{"name":"Leiden University Medical Centre, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Moss","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research, Leiden, The Netherlands"},{"name":"Leiden University Medical Centre, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastiaan J.W.","family":"van Kraaij","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research, Leiden, The Netherlands"},{"name":"Leiden University Medical Centre, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilie","family":"van Brummelen","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica","family":"Klaassen","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renee S.","family":"Martin","sequence":"additional","affiliation":[{"name":"CuraSen Therapeutics, San Carlos, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edgar","family":"Bautista","sequence":"additional","affiliation":[{"name":"CuraSen Therapeutics, San Carlos, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony P.","family":"Ford","sequence":"additional","affiliation":[{"name":"CuraSen Therapeutics, San Carlos, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip H.C.","family":"Kremer","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research, Leiden, The Netherlands"},{"name":"Leiden University Medical Centre, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geert Jan","family":"Groeneveld","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research, Leiden, The Netherlands"},{"name":"Leiden University Medical Centre, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel A.","family":"Vargas","sequence":"additional","affiliation":[{"name":"CuraSen Therapeutics, San Carlos, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2024,8,22]]},"reference":[{"key":"ref001","doi-asserted-by":"publisher","DOI":"10.1016\/0028-3908(87)90058-X"},{"key":"ref002","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(84)90117-3"},{"key":"ref003","doi-asserted-by":"publisher","DOI":"10.2741\/S415"},{"key":"ref004","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22031273"},{"key":"ref005","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-14-05573.1997"},{"key":"ref006","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresrev.2004.02.002"},{"key":"ref007","doi-asserted-by":"publisher","DOI":"10.1177\/1533317513488924"},{"key":"ref008","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)61393-3"},{"key":"ref009","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awg142"},{"key":"ref010","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2007.08.015"},{"key":"ref011","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2015.09.027"},{"key":"ref012","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000005400"},{"key":"ref013","doi-asserted-by":"publisher","DOI":"10.1017\/S1041610208008612"},{"key":"ref014","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(10)70212-X"},{"key":"ref015","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.61.6_suppl_3.S17"},{"key":"ref016","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1331.2008.02103.x"},{"key":"ref017","doi-asserted-by":"publisher","DOI":"10.2165\/00002512-200926030-00002"},{"key":"ref018","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000183056.89590.0d"},{"key":"ref019","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20160"},{"key":"ref020","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2016.11.009"},{"key":"ref021","doi-asserted-by":"publisher","DOI":"10.3233\/JPD-179001"},{"key":"ref022","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.117.190975"},{"key":"ref023","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(19)30400-4"},{"key":"ref024","doi-asserted-by":"publisher","DOI":"10.1007\/s10534-018-0131-5"},{"key":"ref025","doi-asserted-by":"publisher","DOI":"10.1002\/mds.108"},{"key":"ref026","doi-asserted-by":"publisher","DOI":"10.1007\/s11481-018-09831-0"},{"key":"ref027","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf3934"},{"key":"ref028","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25341"},{"key":"ref029","doi-asserted-by":"publisher","DOI":"10.1186\/alzrt175"},{"key":"ref030","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.57"},{"key":"ref031","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.18.10920"},{"key":"ref032","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2016.11.022"},{"key":"ref033","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.193241"},{"key":"ref034","doi-asserted-by":"publisher","DOI":"10.1016\/0163-7258(90)90092-G"},{"key":"ref035","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-003-0835-z"},{"key":"ref036","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042-7158.1984.tb06941.x"},{"key":"ref037","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26424"},{"key":"ref038","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.17.5.427"},{"key":"ref039","first-page":"189","volume":"12","author":"Folstein MF","year":"1975","journal-title":"A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res"},{"key":"ref040","unstructured":"Food and Drug Administration. VENTOLIN HFA (albuterol sulfate) Inhalation Aerosol, www.fda.gov\/medwatch. (2014)."},{"key":"ref041","doi-asserted-by":"publisher","DOI":"10.5694\/j.1326-5377.1972.tb46911.x"},{"key":"ref042","doi-asserted-by":"publisher","DOI":"10.1002\/ange.19800921138"},{"key":"ref043","doi-asserted-by":"publisher","DOI":"10.1016\/j.ddtec.2016.07.004"},{"key":"ref044","unstructured":"Highlights of Prescribing Information - Ventolin HFA, dailymed https:\/\/dailymed.nlm.nih.gov\/dailymed\/fda\/fdaDrugXsl.cfm?setid=938ab43d-bf4c-477f-b918-aabe738d562b&type=display (2021)."},{"key":"ref045","doi-asserted-by":"publisher","DOI":"10.1248\/bpb1978.8.385"},{"key":"ref046","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2021.102873"},{"key":"ref047","doi-asserted-by":"publisher","DOI":"10.1002\/trc2.12257"},{"key":"ref048","doi-asserted-by":"publisher","DOI":"10.1126\/science.181.4100.682"},{"key":"ref049","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-011-2405-2"},{"key":"ref050","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291700014392"},{"key":"ref051","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3628"},{"key":"ref052","volume-title":"Handbook of Experimental Pharmacology","author":"Matt RA"},{"key":"ref053","doi-asserted-by":"publisher","DOI":"10.1016\/j.bjane.2021.06.027"},{"key":"ref054","first-page":"2012","author":"Chen X","journal-title":"Adv Pharmacol Sci"},{"key":"ref055","unstructured":"SchmittJAJ. Serotonin, caffeine and cognition: psychopharmacological studies in human cognitive functioning. PhD Thesis, Maastricht University, 2001."},{"key":"ref056","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1985.tb05120.x"},{"key":"ref057","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1979.tb00454.x"},{"key":"ref058","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1991.122"},{"key":"ref059","author":"van Steveninck AL","year":"1993","journal-title":"PhD Thesis, State University Leiden"},{"key":"ref060","doi-asserted-by":"publisher","DOI":"10.1097\/00004714-199808000-00007"},{"key":"ref061","doi-asserted-by":"publisher","DOI":"10.1159\/000195765"},{"key":"ref062","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2007.10.003"},{"key":"ref063","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.25.11.1065"},{"issue":"1","key":"ref064","first-page":"69S","volume":"18","author":"Borland RG","year":"1984","journal-title":"Br J Clin Pharmacol"},{"key":"ref065","first-page":"27p","volume":"218","author":"Wright BM","year":"1971","journal-title":"J Physiol"},{"key":"ref066","doi-asserted-by":"publisher","DOI":"10.1111\/j.2044-8341.1974.tb02285.x"},{"key":"ref067","doi-asserted-by":"publisher","DOI":"10.1177\/026988119601000208"},{"key":"ref068","doi-asserted-by":"publisher","DOI":"10.1016\/0009-9236(95)90194-9"},{"key":"ref069","doi-asserted-by":"publisher","DOI":"10.1007\/BF02244655"},{"key":"ref070","doi-asserted-by":"publisher","DOI":"10.1159\/000343478"}],"container-title":["Journal of Parkinson\u2019s Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JPD-240039","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.3233\/JPD-240039","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JPD-240039","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T04:53:44Z","timestamp":1777611224000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.3233\/JPD-240039"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,22]]},"references-count":70,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,9,3]]}},"alternative-id":["10.3233\/JPD-240039"],"URL":"https:\/\/doi.org\/10.3233\/jpd-240039","relation":{},"ISSN":["1877-7171","1877-718X"],"issn-type":[{"value":"1877-7171","type":"print"},{"value":"1877-718X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,22]]}}}