{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T22:10:38Z","timestamp":1793139038104,"version":"4.5.0"},"reference-count":67,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,11,6]],"date-time":"2023-11-06T00:00:00Z","timestamp":1699228800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,11,6]],"date-time":"2023-11-06T00:00:00Z","timestamp":1699228800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100013126","name":"FP Pharmaceutical Corporation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013126","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Monoamine oxidase B (MAO-B) inhibitors are used to control Parkinson\u2019s disease (PD). Selegiline, rasagiline, and safinamide are widely used as MAO-B inhibitors worldwide. Although these drugs inhibit MAO-B, there are pharmacological and chemical differences, such as the inhibitory activity, the non-dopaminergic properties in safinamide, and the amphetamine-like structure in selegiline. MAO-B inhibitors may differ in adverse events (AEs). However, differences in actual practical clinics are not fully investigated. A retrospective study was conducted using FAERS, the largest database of spontaneous adverse events. AE signals for MAO-B inhibitors, including selegiline, rasagiline, and safinamide, were detected using the reporting odds ratio method and compared. Hypocomplementemia, hepatic cyst, hepatic function abnormal, liver disorder and cholangitis were detected for selegiline as drug-specific signals. The amphetamine effect was not confirmed for any of the three MAO-B inhibitors. The tyramine reaction was detected as an AE signal only for rasagiline. Moreover, the REM sleep behavior disorder was not detected as an AE signal for safinamide, suggesting that non-dopaminergic effects might be beneficial. Considering the differences in AEs for MAO-B inhibitors will assist with the appropriate PD medication.<\/jats:p>","DOI":"10.1038\/s41598-023-44142-2","type":"journal-article","created":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T10:02:21Z","timestamp":1699351341000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Safety comparisons among monoamine oxidase inhibitors against Parkinson\u2019s disease using FDA adverse event reporting system"],"prefix":"10.1038","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0973-6773","authenticated-orcid":false,"given":"Hiroto","family":"Asano","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8988-9453","authenticated-orcid":false,"given":"Yu-Shi","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9886-1447","authenticated-orcid":false,"given":"Asuka","family":"Hatabu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0044-0722","authenticated-orcid":false,"given":"Tatsuya","family":"Takagi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikiko","family":"Ueda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8299-4464","authenticated-orcid":false,"given":"Kenji","family":"Ikeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,11,6]]},"reference":[{"key":"44142_CR1","doi-asserted-by":"publisher","DOI":"10.3389\/fpubh.2021.776847","volume":"9","author":"Z Ou","year":"2021","unstructured":"Ou, Z. et al. Global trends in the incidence, prevalence, and years lived with disability of Parkinson\u2019s disease in 204 countries\/territories from 1990 to 2019. Front. Public Health 9, 776847 (2021).","journal-title":"Front. Public Health"},{"key":"44142_CR2","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1001\/jama.2019.22360","volume":"323","author":"MJ Armstrong","year":"2020","unstructured":"Armstrong, M. J. & Okun, M. S. Diagnosis and treatment of Parkinson disease: A review. JAMA 323, 548\u2013560 (2020).","journal-title":"JAMA"},{"key":"44142_CR3","doi-asserted-by":"publisher","first-page":"340","DOI":"10.3389\/fphar.2016.00340","volume":"7","author":"JPM Finberg","year":"2016","unstructured":"Finberg, J. P. M. & Rabey, J. M. Inhibitors of MAO-A and MAO-B in psychiatry and neurology. Front. Pharmacol. 7, 340 (2016).","journal-title":"Front. Pharmacol."},{"key":"44142_CR4","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1038\/npp.2014.214","volume":"40","author":"JS Fowler","year":"2015","unstructured":"Fowler, J. S. et al. Evidence that formulations of the selective MAO-B inhibitor, selegiline, which bypass first-pass metabolism, also inhibit MAO-A in the human brain. Neuropsychopharmacology 40, 650\u2013657 (2015).","journal-title":"Neuropsychopharmacology"},{"key":"44142_CR5","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1007\/s00702-019-02082-0","volume":"127","author":"T T\u00e1bi","year":"2020","unstructured":"T\u00e1bi, T., V\u00e9csei, L., Youdim, M. B., Riederer, P. & Sz\u00f6k\u0151, \u00c9. Selegiline: A molecule with innovative potential. J. Neural Transm. 127, 831\u2013842 (2020).","journal-title":"J. Neural Transm."},{"key":"44142_CR6","volume-title":"StatPearls","author":"J Moore","year":"2022","unstructured":"Moore, J., Saadabadi, J. & Selegiline, A. StatPearls (StatPearls Publishing, 2022)."},{"key":"44142_CR7","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1007\/s40520-019-01232-4","volume":"32","author":"D-Q Jiang","year":"2020","unstructured":"Jiang, D.-Q., Li, M.-X., Jiang, L.-L., Chen, X.-B. & Zhou, X.-W. Comparison of selegiline and levodopa combination therapy versus levodopa monotherapy in the treatment of Parkinson\u2019s disease: A meta-analysis. Aging Clin. Exp. Res. 32, 769\u2013779 (2020).","journal-title":"Aging Clin. Exp. Res."},{"key":"44142_CR8","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1007\/BF00634237","volume":"331","author":"JR Fozard","year":"1985","unstructured":"Fozard, J. R., Zreika, M., Robin, M. & Palfreyman, M. G. The functional consequences of inhibition of monoamine oxidase type B: Comparison of the pharmacological properties of L-deprenyl and MDL 72145. Naunyn. Schmiedebergs Arch. Pharmacol. 331, 186\u2013193 (1985).","journal-title":"Naunyn. Schmiedebergs Arch. Pharmacol."},{"key":"44142_CR9","doi-asserted-by":"publisher","first-page":"1075","DOI":"10.1016\/0091-3057(92)90484-W","volume":"43","author":"C Okuda","year":"1992","unstructured":"Okuda, C., Segal, D. S. & Kuczenski, R. Deprenyl alters behavior and caudate dopamine through an amphetamine-like action. Pharmacol. Biochem. Behav. 43, 1075\u20131080 (1992).","journal-title":"Pharmacol. Biochem. Behav."},{"key":"44142_CR10","first-page":"841","volume":"259","author":"G Engberg","year":"1991","unstructured":"Engberg, G., Elebring, T. & Nissbrandt, H. Deprenyl (selegiline), a selective MAO-B inhibitor with active metabolites; effects on locomotor activity, dopaminergic neurotransmission and firing rate of nigral dopamine neurons. J. Pharmacol. Exp. Ther. 259, 841\u2013847 (1991).","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"44142_CR11","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1136\/jnnp.63.2.228","volume":"63","author":"A Churchyard","year":"1997","unstructured":"Churchyard, A., Mathias, C. J., Boonkongchuen, P. & Lees, A. J. Autonomic effects of selegiline: Possible cardiovascular toxicity in Parkinson\u2019s disease. J. Neurol. Neurosurg. Psychiatry 63, 228\u2013234 (1997).","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"44142_CR12","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1111\/j.1600-0404.2005.00294.x","volume":"111","author":"R Stryjer","year":"2005","unstructured":"Stryjer, R., Klein, C., Treves, T. A. & Rabey, J. M. The effects of acute loading with levodopa and levodopa with selegiline on blood pressure and plasma norepinephrine levels in chronic Parkinson\u2019s disease patients. Acta Neurol. Scand. 111, 89\u201394 (2005).","journal-title":"Acta Neurol. Scand."},{"key":"44142_CR13","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1097\/00002826-200009000-00006","volume":"23","author":"J-L Montastruc","year":"2000","unstructured":"Montastruc, J.-L. et al. Adverse drug reactions to selegiline[colon] a review of the French pharmacovigilance database. Clin. Neuropharmacol. 23, 271\u2013275 (2000).","journal-title":"Clin. Neuropharmacol."},{"key":"44142_CR14","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1007\/s00213-005-0200-7","volume":"183","author":"S Yasar","year":"2006","unstructured":"Yasar, S. et al. A comparison of drug-seeking behavior maintained by D-amphetamine, L-deprenyl (selegiline), and D-deprenyl under a second-order schedule in squirrel monkeys. Psychopharmacology (Berl) 183, 413\u2013421 (2006).","journal-title":"Psychopharmacology (Berl)"},{"key":"44142_CR15","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1124\/jpet.105.096263","volume":"317","author":"S Yasar","year":"2006","unstructured":"Yasar, S. et al. Metabolic transformation plays a primary role in the psychostimulant-like discriminative-stimulus effects of selegiline [(R)-(-)-deprenyl]. J. Pharmacol. Exp. Ther. 317, 387\u2013394 (2006).","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"44142_CR16","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1038\/sj.bjp.0703826","volume":"132","author":"MBH Youdim","year":"2001","unstructured":"Youdim, M. B. H., Gross, A. & Finberg, J. P. M. Rasagiline [N-propargyl-1R(+)-aminoindan], a selective and potent inhibitor of mitochondrial monoamine oxidase B. Br. J. Pharmacol. 132, 500\u2013506 (2001).","journal-title":"Br. J. Pharmacol."},{"key":"44142_CR17","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1007\/s00702-012-0927-3","volume":"120","author":"T M\u00fcller","year":"2013","unstructured":"M\u00fcller, T., Hoffmann, J. A., Dimpfel, W. & Oehlwein, C. Switch from selegiline to rasagiline is beneficial in patients with Parkinson\u2019s disease. J. Neural. Transm. 120, 761\u2013765 (2013).","journal-title":"J. Neural. Transm."},{"key":"44142_CR18","doi-asserted-by":"publisher","first-page":"1420","DOI":"10.1177\/0091270010369674","volume":"50","author":"T Goren","year":"2010","unstructured":"Goren, T., Adar, L., Sasson, N. & Weiss, Y. M. Clinical pharmacology tyramine challenge study to determine the selectivity of the monoamine oxidase type B (MAO-B) inhibitor rasagiline. J. Clin. Pharmacol. 50, 1420\u20131428 (2010).","journal-title":"J. Clin. Pharmacol."},{"key":"44142_CR19","unstructured":"DailyMed-AZILECT- rasagiline mesylate tablet. https:\/\/dailymed.nlm.nih.gov\/dailymed\/lookup.cfm?setid=a40d0e73-3f9f-4b01-979d-402c9cdaeb60"},{"key":"44142_CR20","doi-asserted-by":"publisher","first-page":"108","DOI":"10.17925\/ENR.2014.09.02.108","volume":"9","author":"J Kulisevsky","year":"2015","unstructured":"Kulisevsky, J. Emerging role of safinamide in Parkinson\u2019s disease therapy. Eur. Neurol. Rev. 9, 108 (2015).","journal-title":"Eur. Neurol. Rev."},{"key":"44142_CR21","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1080\/14656566.2017.1329819","volume":"18","author":"RM de Souza","year":"2017","unstructured":"de Souza, R. M. & Schapira, A. Safinamide for the treatment of Parkinson\u2019s disease. Expert Opin. Pharmacother. 18, 937\u2013943 (2017).","journal-title":"Expert Opin. Pharmacother."},{"key":"44142_CR22","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1002\/pds.1001","volume":"13","author":"KJ Rothman","year":"2004","unstructured":"Rothman, K. J., Lanes, S. & Sacks, S. T. The reporting odds ratio and its advantages over the proportional reporting ratio. Pharmacoepidemiol. Drug Saf. 13, 519\u2013523 (2004).","journal-title":"Pharmacoepidemiol. Drug Saf."},{"key":"44142_CR23","unstructured":"FAERS Quarterly Data Extract Files. https:\/\/fis.fda.gov\/extensions\/FPD-QDE-FAERS\/FPD-QDE-FAERS.html"},{"key":"44142_CR24","unstructured":"DailyMed-AMPHETAMINE SULFATE-amphetamine tablet. https:\/\/dailymed.nlm.nih.gov\/dailymed\/drugInfo.cfm?setid=828c84a6-a317-4e4d-9521-0c3865ff732f"},{"key":"44142_CR25","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1093\/aje\/kwg068","volume":"157","author":"SK Van Den Eeden","year":"2003","unstructured":"Van Den Eeden, S. K. et al. Incidence of Parkinson\u2019s disease: Variation by age, gender, and race\/ethnicity. Am. J. Epidemiol. 157, 1015\u20131022 (2003).","journal-title":"Am. J. Epidemiol."},{"key":"44142_CR26","doi-asserted-by":"publisher","first-page":"601","DOI":"10.5414\/CP203798","volume":"58","author":"T Mabuchi","year":"2020","unstructured":"Mabuchi, T., Hosomi, K., Yokoyama, S. & Takada, M. Polypharmacy in three different spontaneous adverse drug event databases. Int. J. Clin. Pharmacol. Ther. 58, 601\u2013607 (2020).","journal-title":"Int. J. Clin. Pharmacol. Ther."},{"key":"44142_CR27","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1186\/s12883-017-0904-4","volume":"17","author":"G McLean","year":"2017","unstructured":"McLean, G., Hindle, J. V., Guthrie, B. & Mercer, S. W. Co-morbidity and polypharmacy in Parkinson\u2019s disease: Insights from a large Scottish primary care database. BMC Neurol. 17, 126 (2017).","journal-title":"BMC Neurol."},{"key":"44142_CR28","doi-asserted-by":"publisher","first-page":"990","DOI":"10.1002\/hep.30880","volume":"71","author":"K Kyritsi","year":"2020","unstructured":"Kyritsi, K. et al. Modulation of the tryptophan hydroxylase 1\/monoamine oxidase-A\/5-hydroxytryptamine\/5-hydroxytryptamine receptor 2A\/2B\/2C axis regulates biliary proliferation and liver fibrosis during cholestasis. Hepatology 71, 990\u20131008 (2020).","journal-title":"Hepatology"},{"key":"44142_CR29","first-page":"1480","volume":"29","author":"M Hidestrand","year":"2001","unstructured":"Hidestrand, M. et al. CYP2B6 and CYP2C19 as the major enzymes responsible for the metabolism of selegiline, a drug used in the treatment of Parkinson\u2019s disease, as revealed from experiments with recombinant enzymes. Drug Metab. Dispos. 29, 1480\u20131484 (2001).","journal-title":"Drug Metab. Dispos."},{"key":"44142_CR30","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1007\/s00702-022-02465-w","volume":"129","author":"WH Jost","year":"2022","unstructured":"Jost, W. H. A critical appraisal of MAO-B inhibitors in the treatment of Parkinson\u2019s disease. J. Neural. Transm. (Vienna) 129, 723\u2013736 (2022).","journal-title":"J. Neural. Transm. (Vienna)"},{"key":"44142_CR31","doi-asserted-by":"publisher","first-page":"69","DOI":"10.2133\/dmpk.16.69","volume":"16","author":"T Kubota","year":"2001","unstructured":"Kubota, T., Chiba, K. & Iga, T. Frequency distribution of CYP2C19, CYP2D6, and CYP2C9 mutant-alleles in several different populations. Drug Metab. Pharmacokinet. 16, 69\u201374 (2001).","journal-title":"Drug Metab. Pharmacokinet."},{"key":"44142_CR32","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1097\/WNF.0000000000000239","volume":"40","author":"Y Mizuno","year":"2017","unstructured":"Mizuno, Y. et al. A randomized double-blind placebo-controlled phase III trial of selegiline monotherapy for early Parkinson disease. Clin. Neuropharmacol. 40, 201\u2013207 (2017).","journal-title":"Clin. Neuropharmacol."},{"key":"44142_CR33","doi-asserted-by":"publisher","first-page":"385","DOI":"10.2165\/00002018-200629050-00003","volume":"29","author":"L Hazell","year":"2006","unstructured":"Hazell, L. & Shakir, S. A. W. Under-reporting of adverse drug reactions\u202f: A systematic review. Drug Saf. 29, 385\u2013396 (2006).","journal-title":"Drug Saf."},{"key":"44142_CR34","doi-asserted-by":"publisher","first-page":"1937","DOI":"10.1001\/archneur.59.12.1937","volume":"59","author":"Parkinson Study Group","year":"2002","unstructured":"Parkinson Study Group. A controlled trial of rasagiline in early Parkinson disease: The TEMPO study. Arch. Neurol. 59, 1937\u20131943 (2002).","journal-title":"Arch. Neurol."},{"key":"44142_CR35","doi-asserted-by":"publisher","first-page":"916","DOI":"10.1002\/mds.20145","volume":"19","author":"MB Stern","year":"2004","unstructured":"Stern, M. B. et al. Double-blind, randomized, controlled trial of rasagiline as monotherapy in early Parkinson\u2019s disease patients. Mov. Disord. 19, 916\u2013923 (2004).","journal-title":"Mov. Disord."},{"key":"44142_CR36","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1001\/archneur.62.2.241","volume":"62","author":"Parkinson Study Group","year":"2005","unstructured":"Parkinson Study Group. A randomized placebo-controlled trial of rasagiline in levodopa-treated patients with parkinson disease and motor fluctuations: The PRESTO study. Arch. Neurol. 62, 241\u2013248 (2005).","journal-title":"Arch. Neurol."},{"key":"44142_CR37","doi-asserted-by":"publisher","first-page":"947","DOI":"10.1016\/S0140-6736(05)71083-7","volume":"365","author":"O Rascol","year":"2005","unstructured":"Rascol, O. et al. Rasagiline as an adjunct to levodopa in patients with Parkinson\u2019s disease and motor fluctuations (LARGO, lasting effect in adjunct therapy with rasagiline given once daily, study): A randomised, double-blind, parallel-group trial. Lancet 365, 947\u2013954 (2005).","journal-title":"Lancet"},{"key":"44142_CR38","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1001\/archneur.61.4.561","volume":"61","author":"Parkinson Study Group","year":"2004","unstructured":"Parkinson Study Group. a controlled, randomized, delayed-start study of rasagiline in early Parkinson disease. Arch. Neurol. 61, 561\u2013566 (2004).","journal-title":"Arch. Neurol."},{"key":"44142_CR39","doi-asserted-by":"publisher","first-page":"1268","DOI":"10.1056\/NEJMoa0809335","volume":"361","author":"CW Olanow","year":"2009","unstructured":"Olanow, C. W. et al. A double-blind, delayed-start trial of rasagiline in Parkinson\u2019s disease. N. Engl. J. Med. 361, 1268\u20131278 (2009).","journal-title":"N. Engl. J. Med."},{"key":"44142_CR40","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2020-046329","volume":"11","author":"X Zhang","year":"2021","unstructured":"Zhang, X., Guarin, D., Mohammadzadehhonarvar, N., Chen, X. & Gao, X. Parkinson\u2019s disease and cancer: A systematic review and meta-analysis of over 17 million participants. BMJ Open 11, e046329 (2021).","journal-title":"BMJ Open"},{"key":"44142_CR41","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1002\/pds.5422","volume":"31","author":"CB Johannes","year":"2022","unstructured":"Johannes, C. B. et al. The risk of melanoma with rasagiline compared with other antiparkinsonian medications: A retrospective cohort study in the United States medicare database. Pharmacoepidemiol. Drug Saf. 31, 643\u2013651 (2022).","journal-title":"Pharmacoepidemiol. Drug Saf."},{"key":"44142_CR42","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/j.brainresbull.2020.12.018","volume":"168","author":"H Wasan","year":"2021","unstructured":"Wasan, H., Singh, D. & Kh, R. Safinamide in neurological disorders and beyond: Evidence from preclinical and clinical studies. Brain Res. Bull. 168, 165\u2013177 (2021).","journal-title":"Brain Res. Bull."},{"key":"44142_CR43","doi-asserted-by":"publisher","first-page":"1716","DOI":"10.1002\/mds.21048","volume":"21","author":"JA de Marcaida","year":"2006","unstructured":"de Marcaida, J. A. et al. Effects of tyramine administration in Parkinson\u2019s disease patients treated with selective MAO-B inhibitor rasagiline. Mov. Disord. 21, 1716\u20131721 (2006).","journal-title":"Mov. Disord."},{"key":"44142_CR44","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1016\/j.jocn.2021.07.011","volume":"91","author":"M Plastino","year":"2021","unstructured":"Plastino, M. et al. Effects of safinamide on REM sleep behavior disorder in Parkinson disease: A randomized, longitudinal, cross-over pilot study. J. Clin. Neurosci. 91, 306\u2013312 (2021).","journal-title":"J. Clin. Neurosci."},{"key":"44142_CR45","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1016\/j.smrv.2008.11.003","volume":"13","author":"A Iranzo","year":"2009","unstructured":"Iranzo, A., Santamaria, J. & Tolosa, E. The clinical and pathophysiological relevance of REM sleep behavior disorder in neurodegenerative diseases. Sleep Med. Rev. 13, 385\u2013401 (2009).","journal-title":"Sleep Med. Rev."},{"key":"44142_CR46","doi-asserted-by":"publisher","first-page":"714","DOI":"10.1016\/j.sleep.2013.02.004","volume":"14","author":"P-H Luppi","year":"2013","unstructured":"Luppi, P.-H., Cl\u00e9ment, O., Valencia Garcia, S., Brischoux, F. & Fort, P. New aspects in the pathophysiology of rapid eye movement sleep behavior disorder: The potential role of glutamate, gamma-aminobutyric acid, and glycine. Sleep Med. 14, 714\u2013718 (2013).","journal-title":"Sleep Med."},{"key":"44142_CR47","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1007\/s40801-022-00308-4","volume":"9","author":"G Ronconi","year":"2022","unstructured":"Ronconi, G. et al. Prescription pattern of monoamine oxidase B inhibitors combined with levodopa: A retrospective observational analysis of italian healthcare administrative databases. Drugs Real World Outcomes 9, 391\u2013401 (2022).","journal-title":"Drugs Real World Outcomes"},{"key":"44142_CR48","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1038\/mp.2008.90","volume":"14","author":"SM Berman","year":"2009","unstructured":"Berman, S. M., Kuczenski, R., McCracken, J. T. & London, E. D. Potential adverse effects of amphetamine treatment on brain and behavior: A review. Mol. Psychiatry 14, 123\u2013142 (2009).","journal-title":"Mol. Psychiatry"},{"key":"44142_CR49","first-page":"2343691","volume":"2016","author":"A Sinha","year":"2016","unstructured":"Sinha, A., Lewis, O., Kumar, R., Yeruva, S. L. H. & Curry, B. H. Adult ADHD medications and their cardiovascular implications. Case Rep. Cardiol. 2016, 2343691 (2016).","journal-title":"Case Rep. Cardiol."},{"key":"44142_CR50","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/0736-4679(89)90263-1","volume":"7","author":"RW Derlet","year":"1989","unstructured":"Derlet, R. W., Rice, P., Horowitz, B. Z. & Lord, R. V. Amphetamine toxicity: Experience with 127 cases. J. Emerg. Med. 7, 157\u2013161 (1989).","journal-title":"J. Emerg. Med."},{"key":"44142_CR51","first-page":"299","volume":"112","author":"H Kalant","year":"1975","unstructured":"Kalant, H. & Kalant, O. J. Death in amphetamine users: Causes and rates. Can. Med. Assoc. J. 112, 299\u2013304 (1975).","journal-title":"Can. Med. Assoc. J."},{"key":"44142_CR52","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1126\/science.166.3907.899","volume":"166","author":"JT Coyle","year":"1969","unstructured":"Coyle, J. T. & Snyder, S. H. Antiparkinsonian drugs: Inhibition of dopamine uptake in the corpus striatum as a possible mechanism of action. Science 166, 899\u2013901 (1969).","journal-title":"Science"},{"key":"44142_CR53","unstructured":"Centre, U. M. About VigiBase. https:\/\/who-umc.org\/vigibase\/"},{"key":"44142_CR54","unstructured":"VigiAccess. https:\/\/www.vigiaccess.org\/"},{"key":"44142_CR55","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1007\/s40264-019-00899-y","volume":"43","author":"U Vogel","year":"2020","unstructured":"Vogel, U. et al. Investigating overlap in signals from EVDAS, FAERS, and VigiBase\u00ae. Drug Saf. 43, 351\u2013362 (2020).","journal-title":"Drug Saf."},{"key":"44142_CR56","doi-asserted-by":"publisher","first-page":"20025","DOI":"10.1038\/s41598-019-56525-5","volume":"9","author":"A Poleksic","year":"2019","unstructured":"Poleksic, A. & Xie, L. Database of adverse events associated with drugs and drug combinations. Sci. Rep. 9, 20025 (2019).","journal-title":"Sci. Rep."},{"key":"44142_CR57","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1186\/s12911-020-1053-z","volume":"20","author":"X Yao","year":"2020","unstructured":"Yao, X. et al. Mining and visualizing high-order directional drug interaction effects using the FAERS database. BMC Med. Inform. Decis. Mak. 20, 50 (2020).","journal-title":"BMC Med. Inform. Decis. Mak."},{"key":"44142_CR58","unstructured":"Research, C. for D. E. and. Good Pharmacovigilance Practices and Pharmacoepidemiologic Assessment. https:\/\/www.fda.gov\/regulatory-information\/search-fda-guidance-documents\/good-pharmacovigilance-practices-and-pharmacoepidemiologic-assessment (2020)."},{"key":"44142_CR59","unstructured":"ISO-ISO 3166\u2014Country Codes. ISO https:\/\/www.iso.org\/iso-3166-country-codes.html"},{"key":"44142_CR60","unstructured":"KEGG DRUG Database. https:\/\/www.genome.jp\/kegg\/drug\/"},{"key":"44142_CR61","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1093\/nar\/28.1.27","volume":"28","author":"M Kanehisa","year":"2000","unstructured":"Kanehisa, M. & Goto, S. KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 28, 27\u201330 (2000).","journal-title":"Nucleic Acids Res."},{"key":"44142_CR62","doi-asserted-by":"publisher","first-page":"1947","DOI":"10.1002\/pro.3715","volume":"28","author":"M Kanehisa","year":"2019","unstructured":"Kanehisa, M. Toward understanding the origin and evolution of cellular organisms. Protein Sci. 28, 1947\u20131951 (2019).","journal-title":"Protein Sci."},{"key":"44142_CR63","doi-asserted-by":"publisher","first-page":"D545","DOI":"10.1093\/nar\/gkaa970","volume":"49","author":"M Kanehisa","year":"2021","unstructured":"Kanehisa, M., Furumichi, M., Sato, Y., Ishiguro-Watanabe, M. & Tanabe, M. KEGG: Integrating viruses and cellular organisms. Nucleic Acids Res. 49, D545\u2013D551 (2021).","journal-title":"Nucleic Acids Res."},{"key":"44142_CR64","unstructured":"MedDRA. https:\/\/www.meddra.org\/"},{"key":"44142_CR65","unstructured":"UNSD\u2014Methodology. https:\/\/unstats.un.org\/unsd\/methodology\/m49\/"},{"key":"44142_CR66","doi-asserted-by":"publisher","first-page":"1402","DOI":"10.1002\/pds.4672","volume":"27","author":"C Fukazawa","year":"2018","unstructured":"Fukazawa, C., Hinomura, Y., Kaneko, M. & Narukawa, M. Significance of data mining in routine signal detection: Analysis based on the safety signals identified by the FDA. Pharmacoepidemiol. Drug Saf. 27, 1402\u20131408 (2018).","journal-title":"Pharmacoepidemiol. Drug Saf."},{"key":"44142_CR67","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1007\/BF01202268","volume":"12","author":"V Batagelj","year":"1995","unstructured":"Batagelj, V. & Bren, M. Comparing resemblance measures. J. Classif. 12, 73\u201390 (1995).","journal-title":"J. Classif."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-44142-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-44142-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-44142-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T10:05:21Z","timestamp":1699351521000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-44142-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,6]]},"references-count":67,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["44142"],"URL":"https:\/\/doi.org\/10.1038\/s41598-023-44142-2","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,6]]},"assertion":[{"value":"2 November 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 October 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 November 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"19272"}}