{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T11:58:43Z","timestamp":1740139123076,"version":"3.37.3"},"reference-count":75,"publisher":"American Physiological Society","issue":"6","funder":[{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["17AIREA33660433"],"award-info":[{"award-number":["17AIREA33660433"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001463","name":"American Society of Nephrology","doi-asserted-by":"publisher","award":["C06RR0306551"],"award-info":[{"award-number":["C06RR0306551"]}],"id":[{"id":"10.13039\/100001463","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R15GM107949"],"award-info":[{"award-number":["R15GM107949"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R15HL154067"],"award-info":[{"award-number":["R15HL154067"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.physiology.org"],"crossmark-restriction":true},"short-container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"published-print":{"date-parts":[[2021,6,1]]},"abstract":"<jats:p>Donepezil is a centrally acting acetylcholinesterase (AChE) inhibitor with therapeutic potential in inflammatory diseases; however, the underlying autonomic and cholinergic mechanisms remain unclear. Here, we assessed effects of donepezil on mean arterial pressure (MAP), heart rate (HR), HR variability, and body temperature in conscious adult male C57BL\/6 mice to investigate the autonomic pathways involved. Central versus peripheral cholinergic effects of donepezil were assessed using pharmacological approaches including comparison with the peripherally acting AChE inhibitor, neostigmine. Drug treatments included donepezil (2.5 or 5\u2009mg\/kg sc), neostigmine methyl sulfate (80 or 240\u2009\u03bcg\/kg ip), atropine sulfate (5\u2009mg\/kg ip), atropine methyl bromide (5\u2009mg\/kg ip), or saline. Donepezil, at 2.5 and 5\u2009mg\/kg, decreased HR by 36\u2009\u00b1\u20094% and 44\u2009\u00b1\u20093% compared with saline ( n = 10, P &lt; 0.001). Donepezil, at 2.5 and 5\u2009mg\/kg, decreased temperature by 13\u2009\u00b1\u20092% and 22\u2009\u00b1\u20092% compared with saline ( n = 6, P &lt; 0.001). Modest ( P &lt; 0.001) increases in MAP were observed with donepezil after peak bradycardia occurred. Atropine sulfate and atropine methyl bromide blocked bradycardic responses to donepezil, but only atropine sulfate attenuated hypothermia. The pressor response to donepezil was similar in mice coadministered atropine sulfate; however, coadministration of atropine methyl bromide potentiated the increase in MAP. Neostigmine did not alter HR or temperature, but did result in early increases in MAP. Despite the marked bradycardia, donepezil did not increase normalized high-frequency HR variability. We conclude that donepezil causes marked bradycardia and hypothermia in conscious mice via the activation of muscarinic receptors while concurrently increasing MAP via autonomic and cholinergic pathways that remain to be elucidated.<\/jats:p>","DOI":"10.1152\/ajpregu.00360.2019","type":"journal-article","created":{"date-parts":[[2021,4,14]],"date-time":"2021-04-14T12:01:17Z","timestamp":1618401677000},"page":"R871-R884","update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Autonomic and cholinergic mechanisms mediating cardiovascular and temperature effects of donepezil in conscious mice"],"prefix":"10.1152","volume":"320","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0347-663X","authenticated-orcid":false,"given":"Aaron J.","family":"Polichnowski","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee"},{"name":"Center of Excellence in Inflammation, Infectious Disease and Immunity, East Tennessee State University, Johnson City, Tennessee"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geoffrey A.","family":"Williamson","sequence":"additional","affiliation":[{"name":"Department of Electrical and Computer Engineering, Illinois Institute of Technology, Chicago, Illinois"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tesha E.","family":"Blair","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0845-2488","authenticated-orcid":false,"given":"Donald B.","family":"Hoover","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee"},{"name":"Center of Excellence in Inflammation, Infectious Disease and Immunity, East Tennessee State University, Johnson City, Tennessee"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcna.2018.10.009"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14030"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/nm1124"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/nature01339"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1126\/science.1209985"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0600506103"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.93340"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2013.268573"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-014-0504-2"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2008.06.011"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pa.22.040182.002013"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/S0300-483X(99)00121-3"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.ntt.2006.10.004"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.2000.278.1.R215"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.2000.279.6.R2214"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0773.2001.d01-133.x"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1126\/science.6166045"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2013.00222"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2000.279.2.H733"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.2007.040733"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1007\/s00268-005-0073-2"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/8274903"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1177\/026988110001400301"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2004.11.042"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1097\/01.CCM.0B013E31816208B3"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2013.06.023"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0062679"},{"key":"B28","first-page":"216","volume":"133","author":"Long JP","year":"1961","journal-title":"J Pharmacol Exp Ther"},{"key":"B29","first-page":"146","volume":"257","author":"Padmanabha Pillai N","year":"1982","journal-title":"Arch Int Pharmacodyn Ther"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1186\/1471-230X-14-148"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2007.02.039"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1955.tb00882.x"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2010-100681"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0000000000000272"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.2008.04895.x"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2006.11.069"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2014.08.026"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.2003.02588.x"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1023\/a:1022844517200"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.02.022"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2015.03.006"},{"key":"B42","first-page":"3","volume":"58","author":"Pires W","year":"2007","journal-title":"J Physiol Pharmacol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.2174\/1570159x11311030006"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1000157"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1097\/00000441-198701000-00005"},{"volume-title":"StatPearls","year":"2021","author":"Pakala RS","key":"B46"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00362.2017"},{"key":"B48","doi-asserted-by":"crossref","first-page":"S89","DOI":"10.33549\/physiolres.930000.55.S1.89","volume":"55","author":"Bernatova I","year":"2006","journal-title":"Physiol Res"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/s0091-3057(03)00012-1"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01136.2003"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/j.autneu.2014.11.007"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00591.2014"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2016.06.070"},{"key":"B54","first-page":"179","volume":"48","author":"Buccafusco JJ","year":"1996","journal-title":"Pharmacol Rev"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0702678"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1016\/s0014-2999(98)00717-1"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00170.2009"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2005.12.009"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtherbio.2018.08.014"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1093\/ajh\/hpv017"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyg.2014.01040"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1007\/s12576-009-0071-5"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2013.00026"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1111\/psyp.13287"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1111\/anec.12148"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2002.017483"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2001.280.6.H2804"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.93.5.1043"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2011.00086"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.59.2.178"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1042\/cs0880103"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00361.2014"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.98.6.547"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1007\/s00421-009-1295-z"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.2001.281.3.R683"}],"container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.physiology.org\/doi\/pdf\/10.1152\/ajpregu.00360.2019","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,24]],"date-time":"2022-12-24T08:09:20Z","timestamp":1671869360000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.physiology.org\/doi\/10.1152\/ajpregu.00360.2019"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,1]]},"references-count":75,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,6,1]]}},"alternative-id":["10.1152\/ajpregu.00360.2019"],"URL":"https:\/\/doi.org\/10.1152\/ajpregu.00360.2019","relation":{},"ISSN":["0363-6119","1522-1490"],"issn-type":[{"type":"print","value":"0363-6119"},{"type":"electronic","value":"1522-1490"}],"subject":[],"published":{"date-parts":[[2021,6,1]]},"assertion":[{"value":"2019-12-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-04-09","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-04-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-06-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}