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Entacapone/Tolcapone/Opicapone for Treating Parkinson’s Disease

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NeuroPsychopharmacotherapy

Abstract

Compounds, which inhibit enzyme activity of catechol-O-methyltransferease, are commonly employed in combination with levodopa/dopadecarboxylase inhibitor formulations in patients with Parkinson’s disease. They ameliorate wearing-off symptoms by prolongation of the peripheral half-life of levodopa, increase of the peripheral levodopa bioavailability, and decline of peripheral ups and downs of levodopa in plasma. Three catechol-O-methyltransferase inhibitors are currently approved. Two of them, the peripherally acting entacapone and, additionally, also centrally acting tolcapone induce a fluctuating enzyme inhibition and aks for more frequent daily oral intake. Opicapone provides a more continuous decline of enzyme activity and must be taken one time daily only. All marketed agents are predominantly used for the treatment of wearing off phenomena in patients with Parkinson’s disease. Inhibitors of catechol-O-methyltransferase do not improve levodopa associated dyskinesia but they reduce number of intakes of oral formulations, which contain levodopa plus a dopa decarboxylase inhibitor.

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References

  • Adler CH, Singer C, O’Brien C, Hauser RA, Lew MF, Marek KL, et al. Randomized, placebo-controlled study of tolcapone in patients with fluctuating Parkinson disease treated with levodopa-carbidopa. Tolcapone Fluctuator Study Group III. Arch Neurol. 1998;55(8):1089–95.

    CAS  PubMed  Google Scholar 

  • Agid Y, Destee A, Durif F, Montastruc JL, Pollak P. Tolcapone, bromocriptine, and Parkinson’s disease. French Tolcapone Study Group. Lancet. 1997;350(9079):712–3.

    CAS  PubMed  Google Scholar 

  • Agid Y, Destee A, Durif F, Montastruc JL, Pedarriosse AM, Deptula D, et al. Efficacy and tolerability of tolcapone compared with bromocriptine in levodopa-treated parkinsonian patients. Mov Disord. 1999;14(1):38–44.

    Google Scholar 

  • Agid Y, Oertel W, Factor S. Entacapone to tolcapone switch study: multicenter double-blind, randomized, active-controlled trial in advanced Parkinson’s disease. Mov Disord. 2005;20:S94.

    Google Scholar 

  • Almeida L, Rocha JF, Falcao A, Palma PN, Loureiro AI, Pinto R, et al. Pharmacokinetics, pharmacodynamics and tolerability of opicapone, a novel catechol-O-methyltransferase inhibitor, in healthy subjects: prediction of slow enzyme-inhibitor complex dissociation of a short-living and very long-acting inhibitor. Clin Pharmacokinet. 2013;52(2):139–51.

    CAS  PubMed  Google Scholar 

  • Apud JA, Mattay V, Chen J, Kolachana BS, Callicott JH, Rasetti R, et al. Tolcapone improves cognition and cortical information processing in normal human subjects. Neuropsychopharmacology. 2007;32(5):1011–20.

    CAS  PubMed  Google Scholar 

  • Baas H, Beiske AG, Ghika J, Jackson M, Oertel WH, Poewe W, et al. Catechol-O-methyltransferase inhibition with tolcapone reduces the “wearing off” phenomenon and levodopa requirements in fluctuating parkinsonian patients. J Neurol Neurosurg Psychiatry. 1997;63(4):421–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bonifacio MJ, Sutcliffe JS, Torrao L, Wright LC, Soares-da-Silva P. Brain and peripheral pharmacokinetics of levodopa in the cynomolgus monkey following administration of opicapone, a third generation nitrocatechol COMT inhibitor. Neuropharmacology. 2014;77:334–41.

    CAS  PubMed  Google Scholar 

  • Borges N. Tolcapone in Parkinson’s disease: liver toxicity and clinical efficacy. Expert Opin Drug Saf. 2005;4(1):69–73.

    CAS  PubMed  Google Scholar 

  • Brooks DJ, Sagar H. Entacapone is beneficial in both fluctuating and non-fluctuating patients with Parkinson’s disease: a randomised, placebo controlled, double blind, six month study. J Neurol Neurosurg Psychiatry. 2003;74(8):1071–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Brooks DJ, Agid Y, Eggert K, Widner H, Ostergaard K, Holopainen A. Treatment of end-of-dose wearing-off in parkinson’s disease: stalevo (levodopa/carbidopa/entacapone) and levodopa/DDCI given in combination with Comtess/Comtan (entacapone) provide equivalent improvements in symptom control superior to that of traditional levodopa/DDCI treatment. Eur Neurol. 2005;53(4):197–202.

    CAS  PubMed  Google Scholar 

  • Ceravolo R, Piccini P, Bailey DL, Jorga KM, Bryson H, Brooks DJ. 18F-dopa PET evidence that tolcapone acts as a central COMT inhibitor in Parkinson’s disease. Synapse. 2002;43(3):201–7.

    CAS  PubMed  Google Scholar 

  • Deane KH, Spieker S, Clarke CE. Catechol-O-methyltransferase inhibitors versus active comparators for levodopa-induced complications in Parkinson’s disease. Cochrane Database Syst Rev. 2004;4:CD004553.

    Google Scholar 

  • Dingemanse J, Jorga KM, Schmitt M, Gieschke R, Fotteler B, Zurcher G, et al. Integrated pharmacokinetics and pharmacodynamics of the novel catechol-O-methyltransferase inhibitor tolcapone during first administration to humans. Clin Pharmacol Ther. 1995;57(5):508–17.

    CAS  PubMed  Google Scholar 

  • Dupont E, Burgunder JM, Findley LJ, Olsson JE, Dorflinger E. Tolcapone added to levodopa in stable parkinsonian patients: a double-blind placebo-controlled study. Tolcapone in Parkinson’s Disease Study Group II (TIPS II). Mov Disord. 1997;12(6):928–34.

    CAS  PubMed  Google Scholar 

  • Factor SA, Molho ES, Feustel PJ, Brown DL, Evans SM. Long-term comparative experience with tolcapone and entacapone in advanced Parkinson’s disease. Clin Neuropharmacol. 2001;24(5):295–9.

    CAS  PubMed  Google Scholar 

  • Feirreira JJ, Rocha JF, Falcao A, Pinto R, Nunes T. Effect of opicapone multiple-dose regimens on levodopa pharmacokinetics, motor response, and erythrocyte-COMT activity in Parkinson’s patients co-administered with levodopa/dopa-decarboxylase inhibitor. J Neurol Sci. 2013;333:e109–51.

    Google Scholar 

  • Gervas JJ, Muradas V, Bazan E, Aguado EG, de Yebenes JG. Effects of 3-OM-dopa on monoamine metabolism in rat brain. Neurology. 1983;33(3):278–82.

    CAS  PubMed  Google Scholar 

  • Goncalves D, Alves G, Soares-da-Silva P, Falcao A. Bioanalytical chromatographic methods for the determination of catechol-O-methyltransferase inhibitors in rodents and human samples: a review. Anal Chim Acta. 2012;710:17–32.

    CAS  PubMed  Google Scholar 

  • Goncalves D, Alves G, Fortuna A, Soares-da-Silva P, Falcao A. An HPLC-DAD method for the simultaneous quantification of opicapone (BIA 9-1067) and its active metabolite in human plasma. Analyst. 2013;138(8):2463–9.

    CAS  PubMed  Google Scholar 

  • Grosset D. Therapy adherence issues in Parkinson’s disease. J Neurol Sci. 2010;289(1–2):115–8.

    PubMed  Google Scholar 

  • Guttman M, Leger G, Reches A, Evans A, Kuwabara H, Cedarbaum JM, et al. Administration of the new COMT inhibitor OR-611 increases striatal uptake of fluorodopa. Mov Disord. 1993;8(3):298–304.

    CAS  PubMed  Google Scholar 

  • Hauser RA. Levodopa/carbidopa/entacapone (Stalevo). Neurology. 2004;62(1 Suppl 1):S64–71.

    CAS  PubMed  Google Scholar 

  • Hauser RA, Molho E, Shale H, Pedder S, Dorflinger EE. A pilot evaluation of the tolerability, safety, and efficacy of tolcapone alone and in combination with oral selegiline in untreated Parkinson’s disease patients. Tolcapone De Novo Study Group. Mov Disord. 1998;13(4):643–7.

    CAS  PubMed  Google Scholar 

  • Hauser RA, Panisset G, Abbruzzese G, Manzione L, Dronamraju R, Kakarieka A. Double-blind trial of levodopa/carbidopa/entacapone versus levodopa/carbidopa in early Parkinson’s disease. Mov Disord. 2008;24:39–48.

    Google Scholar 

  • Hauser RA, Panisset M, Abbruzzese G, Mancione L, Dronamraju N, Kakarieka A. Double-blind trial of levodopa/carbidopa/entacapone versus levodopa/carbidopa in early Parkinson’s disease. Mov Disord. 2009;24(4):541–50.

    PubMed  Google Scholar 

  • Jorga KM. Pharmacokinetics, pharmacodynamics, and tolerability of tolcapone: a review of early studies in volunteers. Neurology. 1998;50(5 Suppl 5):S31–8.

    CAS  PubMed  Google Scholar 

  • Kaakkola S. Clinical pharmacology, therapeutic use and potential of COMT inhibitors in Parkinson’s disease. Drugs. 2000;59(6):1233–50.

    CAS  PubMed  Google Scholar 

  • Kaakkola S, Gordin A, Mannisto PT. General properties and clinical possibilities of new selective inhibitors of catechol O-methyltransferase. Gen Pharmacol. 1994;25(5):813–24.

    CAS  PubMed  Google Scholar 

  • Kieburtz K, Hubble J. Benefits of COMT inhibitors in levodopa-treated parkinsonian patients: results of clinical trials. Neurology. 2000;55(11 Suppl 4):S42–5.

    CAS  PubMed  Google Scholar 

  • Kiss LE, Soares-da-Silva P. Medicinal chemistry of catechol O-methyltransferase (COMT) inhibitors and their therapeutic utility. J Med Chem. 2014;57(21):8692–717.

    CAS  PubMed  Google Scholar 

  • Kiss LE, Ferreira HS, Torrao L, Bonifacio MJ, Palma PN, Soares-da-Silva P, et al. Discovery of a long-acting, peripherally selective inhibitor of catechol-O-methyltransferase. J Med Chem. 2010;53(8):3396–411.

    CAS  PubMed  Google Scholar 

  • Koller W, Lees A, Doder M, Hely M. Randomized trial of tolcapone versus pergolide as add-on to levodopa therapy in Parkinson’s disease patients with motor fluctuations. Mov Disord. 2001;16(5):858–66.

    CAS  PubMed  Google Scholar 

  • Koller W, Guarnieri M, Hubble J, Rabinowicz AL, Silver D. An open-label evaluation of the tolerability and safety of Stalevo (carbidopa, levodopa and entacapone) in Parkinson’s disease patients experiencing wearing-off. J Neural Transm. 2005;112(2):221–30.

    CAS  PubMed  Google Scholar 

  • Kurth MC, Adler CH, Hilaire MS, Singer C, Waters C, LeWitt P, et al. Tolcapone improves motor function and reduces levodopa requirement in patients with Parkinson’s disease experiencing motor fluctuations: a multicenter, double-blind, randomized, placebo-controlled trial. Tolcapone Fluctuator Study Group I. Neurology. 1997;48(1):81–7.

    CAS  PubMed  Google Scholar 

  • Lees AJ, Ferreira JJ, Costa R, Rocha JF, Oliveira C, Lopes N. Efficacy and safety of opicapone, a new COMT-inhibitor, for the treatment of motor fluctuations in Parkinson’s disease patients: BIPARK-II study. J Neurol Sci. 2013;333:e109–51.

    Google Scholar 

  • Maltete D, Cottard AM, Mihout B, Costentin J. Erythrocytes catechol-O-methyl transferase activity is up-regulated after a 3-month treatment by entacapone in parkinsonian patients. Clin Neuropharmacol. 2011;34(1):21–3.

    CAS  PubMed  Google Scholar 

  • Mannisto PT. Catechol O-methyltransferase: characterization of the protein, its gene, and the preclinical pharmacology of COMT inhibitors. Adv Pharmacol. 1998;42:324–8.

    CAS  PubMed  Google Scholar 

  • Mannisto PT, Tuomainen P, Tuominen RK. Different in vivo properties of three new inhibitors of catechol O-methyltransferase in the rat. Br J Pharmacol. 1992;105(3):569–74.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Martignoni E, Cosentino M, Ferrari M, Porta G, Mattarucchi E, Marino F, et al. Two patients with COMT inhibitor-induced hepatic dysfunction and UGT1A9 genetic polymorphism. Neurology. 2005;65(11):1820–2.

    CAS  PubMed  Google Scholar 

  • Müller T. Tolcapone in the management of Parkinson’s disease. Aging Health. 2006; 2(5). https://doi.org/10.2217/1745509X.2.5.709

  • Müller T. Levodopa/carbidopa and entacapone in the treatment of Parkinson’s disease: efficacy, safety and patient preference. Patient Prefer Adherence. 2009;3:51–9.

    PubMed  PubMed Central  Google Scholar 

  • Müller T. Entacapone. Expert Opin Drug Metab Toxicol. 2010;6(8):983–93.

    PubMed  Google Scholar 

  • Müller T, Woitalla D, Schulz D, Peters S, Kuhn W, Przuntek H. Tolcapone increases maximum concentration of levodopa. J Neural Transm. 2000;107(1):113–9.

    CAS  PubMed  Google Scholar 

  • Müller T, Erdmann C, Muhlack S, Bremen D, Przuntek H, Goetze O, et al. Pharmacokinetic behaviour of levodopa and 3-O-methyldopa after repeat administration of levodopa/carbidopa with and without entacapone in patients with Parkinson’s disease. J Neural Transm. 2006;11:1441–8.

    Google Scholar 

  • Myllyla V, Haapaniemi T, Kaakkola S, Kinnunen E, Hartikainen P, Nuutinen J, et al. Patient satisfaction with switching to Stalevo: an open-label evaluation in PD patients experiencing wearing-off (Simcom study). Acta Neurol Scand. 2006;114(3):181–6.

    CAS  PubMed  Google Scholar 

  • Napolitano A, Zurcher G, Da Prada M. Effects of tolcapone, a novel catechol-O-methyltransferase inhibitor, on striatal metabolism of l-dopa and dopamine in rats. Eur J Pharmacol. 1995;273(3):215–21.

    CAS  PubMed  Google Scholar 

  • Nunes T, Rocha JF, Pinto R, Machado R, Wright LC, Falcao A, et al. Pharmacokinetics, pharmacodynmics and tolerability of opicapone, a novel COMT inhibitor, during first administration to healthy male subjects. Parkinsonism Relat Disord. 2012;18S2:S81–S159. Ref Type: Abstract.

    Google Scholar 

  • Nutt JG, Woodward WR, Gancher ST, Merrick D. 3-O-methyldopa and the response to levodopa in Parkinson’s disease. Ann Neurol. 1987;21(6):584–8.

    CAS  PubMed  Google Scholar 

  • Nyholm D, Johansson A, Lennernas H, Askmark H. Levodopa infusion combined with entacapone or tolcapone in Parkinson disease: a pilot trial. Eur J Neurol. 2012;19(6):820–6.

    CAS  PubMed  Google Scholar 

  • Olanow CW, Kieburtz K, Stern M, Watts R, Langston JW, Guarnieri M, et al. Double-blind, placebo-controlled study of entacapone in levodopa-treated patients with stable Parkinson disease. Arch Neurol. 2004;61(10):1563–8.

    CAS  PubMed  Google Scholar 

  • Onofrj M, Thomas A, Iacono D, Di Iorio A, Bonanni L. Switch-over from tolcapone to entacapone in severe Parkinson’s disease patients. Eur Neurol. 2001;46(1):11–6.

    CAS  PubMed  Google Scholar 

  • Palma PN, Bonifacio MJ, Loureiro AI, Soares-da-Silva P. Computation of the binding affinities of catechol-O-methyltransferase inhibitors: multisubstate relative free energy calculations. J Comput Chem. 2012;33(9):970–86.

    CAS  PubMed  Google Scholar 

  • Parkinson Study Group. Entacapone improves motor fluctuations in levodopa-treated Parkinson’s disease patients. Ann Neurol. 1997;42(5):747–55.

    Google Scholar 

  • Poewe WH, Deuschl G, Gordin A, Kultalahti ER, Leinonen M. Efficacy and safety of entacapone in Parkinson’s disease patients with suboptimal levodopa response: a 6-month randomized placebo-controlled double-blind study in Germany and Austria (Celomen study). Acta Neurol Scand. 2002;105(4):245–55.

    CAS  PubMed  Google Scholar 

  • Rajput AH, Martin W, Saint-Hilaire MH, Dorflinger E, Pedder S. Tolcapone improves motor function in parkinsonian patients with the “wearing-off” phenomenon: a double-blind, placebo-controlled, multicenter trial. Neurology. 1997;49(4):1066–71.

    CAS  PubMed  Google Scholar 

  • Rajput AH, Martin W, Saint-Hilaire MH, Dorflinger E, Pedder S. Tolcapone improves motor function in parkinsonian patients with the “wearing-off” phenomenon: a double-blind, placebo-controlled, multicenter trial. Neurology. 1998;50(5 Suppl 5):S54–9.

    CAS  PubMed  Google Scholar 

  • Richy FF, Pietri G, Moran KA, Senior E, Makaroff LE. Compliance with pharmacotherapy and direct healthcare costs in patients with Parkinson’s disease: a retrospective claims database analysis. Appl Health Econ Health Policy. 2013;11(4):395–406.

    PubMed  PubMed Central  Google Scholar 

  • Rinne UK, Larsen JP, Siden A, Worm-Petersen J. Entacapone enhances the response to levodopa in parkinsonian patients with motor fluctuations. Nomecomt Study Group. Neurology. 1998;51(5):1309–14.

    CAS  PubMed  Google Scholar 

  • Rocha JF, Almeida L, Falcao A, Palma PN, Loureiro AI, Pinto R, et al. Opicapone: a short lived and very long acting novel catechol-O-methyltransferase inhibitor following multiple dose administration in healthy subjects. Br J Clin Pharmacol. 2013;76(5):763–75.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ruottinen HM, Rinne UK. A double-blind pharmacokinetic and clinical dose-response study of entacapone as an adjuvant to levodopa therapy in advanced Parkinson’s disease. Clin Neuropharmacol. 1996a;19(4):283–96.

    CAS  PubMed  Google Scholar 

  • Ruottinen HM, Rinne UK. Effect of one month’s treatment with peripherally acting catechol-O-methyltransferase inhibitor, entacapone, on pharmacokinetics and motor response to levodopa in advanced parkinsonian patients. Clin Neuropharmacol. 1996b;19(3):222–33.

    CAS  PubMed  Google Scholar 

  • Ruottinen HM, Rinne UK. Entacapone prolongs levodopa response in a one month double blind study in parkinsonian patients with levodopa related fluctuations. J Neurol Neurosurg Psychiatry. 1996c;60(1):36–40.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Russ H, Muller T, Woitalla D, Rahbar A, Hahn J, Kuhn W. Detection of tolcapone in the cerebrospinal fluid of parkinsonian subjects. Naunyn Schmiedeberg’s Arch Pharmacol. 1999;360(6):719–20.

    CAS  Google Scholar 

  • Sawle GV, Burn DJ, Morrish PK, Lammertsma AA, Snow BJ, Luthra S, et al. The effect of entacapone (OR-611) on brain [18F]-6-l-fluorodopa metabolism: implications for levodopa therapy of Parkinson’s disease. Neurology. 1994;44(7):1292–7.

    CAS  PubMed  Google Scholar 

  • Sedek G, Jorga K, Schmitt M, Burns RS, Leese P. Effect of tolcapone on plasma levodopa concentrations after coadministration with levodopa/carbidopa to healthy volunteers. Clin Neuropharmacol. 1997;20(6):531–41.

    CAS  PubMed  Google Scholar 

  • Seeberger LC, Hauser RA. Levodopa/carbidopa/entacapone in Parkinson’s disease. Expert Rev Neurother. 2009;9(7):929–40.

    CAS  PubMed  Google Scholar 

  • Sethi KD, Hauser RA, Isaacson SH, McClain T. Levodopa/carbidopa/entacapone 200/50/200 mg (Stalevo 200) in the treatment of Parkinson’s disease: a case series. Cases J. 2009;2:7134.

    PubMed  PubMed Central  Google Scholar 

  • Stocchi F, Kieburtz K, Rascol O, Poewe W, Jankovic J, Tolosa E, et al. Initiating levodopa/carbidopa therapy with and without entacapone in early Parkinson’s disease: the Stride-PD Study. Ann Neurol. 2010;68:18–27.

    CAS  PubMed  Google Scholar 

  • Tuomainen P, Reenila I, Mannisto PT. Validation of assay of catechol-O-methyltransferase activity in human erythrocytes. J Pharm Biomed Anal. 1996;14(5):515–23.

    CAS  PubMed  Google Scholar 

  • Waters C. Practical issues with COMT inhibitors in Parkinson’s disease. Neurology. 2000;55(11 Suppl 4):S57–9.

    CAS  PubMed  Google Scholar 

  • Waters CH, Kurth M, Bailey P, Shulman LM, LeWitt P, Dorflinger E, et al. Tolcapone in stable Parkinson’s disease: efficacy and safety of long-term treatment. The Tolcapone Stable Study Group. Neurology. 1997;49(3):665–71.

    CAS  PubMed  Google Scholar 

  • Waters CH, Kurth M, Bailey P, Shulman LM, LeWitt P, Dorflinger E, et al. Tolcapone in stable Parkinson’s disease: efficacy and safety of long-term treatment. Tolcapone Stable Study Group. Neurology. 1998;50(5 Suppl 5):S39–45.

    CAS  PubMed  Google Scholar 

  • Zurcher G, Keller HH, Kettler R, Borgulya J, Bonetti EP, Eigenmann R, et al. Ro 40-7592, a novel, very potent, and orally active inhibitor of catechol-O-methyltransferase: a pharmacological study in rats. Adv Neurol. 1990;53:497–503.

    CAS  PubMed  Google Scholar 

  • Zurcher G, Dingemanse J, Da Prada M. Potent COMT inhibition by Ro 40-7592 in the periphery and in the brain. Preclinical and clinical findings. Adv Neurol. 1993;60:641–7.

    CAS  PubMed  Google Scholar 

  • Zurcher G, Da Prada M, Dingemanse J. Assessment of catechol-O-methyltransferase activity and its inhibition in erythrocytes of animals and humans. Biomed Chromatogr. 1996;10(1):32–6.

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Neurology, St. Joseph Hospital Berlin-Weißensee, Berlin, Germany

    Thomas Müller

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  1. Thomas Müller
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Correspondence to Thomas Müller .

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Editors and Affiliations

  1. Dept Psychiatry , Psychosomatics & Psychotherapy, University of Würzburg, Medical School Clinical Neurochemistry, Würzburg, Germany

    Peter Riederer

  2. Inst für Psychologische Medizin, Haag, Bayern, Germany

    Gerd Laux

  3. Department of Psychiatry, University of Toronto Department of Psychiatry, Toronto, ON, Canada

    Benoit Mulsant

  4. Center Translational Res Neurol Diseases, Dalian Med Uni Shanghai Inst Health Sc Center Translational Res Neurol Diseases, Dalian, China

    Weidong Le

  5. Fujita Health University School Medicine, Toyoake, Aichi, Japan

    Toshiharu Nagatsu

Section Editor information

  1. Center for Research Promotion and Support, Fujita Health University School of Medicine, Toyoake, Aichi, Japan

    Toshiharu Nagatsu

  2. Department of Physiological Chemistry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan

    Akira Nakashima

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Müller, T. (2020). Entacapone/Tolcapone/Opicapone for Treating Parkinson’s Disease. In: Riederer, P., Laux, G., Mulsant, B., Le, W., Nagatsu, T. (eds) NeuroPsychopharmacotherapy. Springer, Cham. https://doi.org/10.1007/978-3-319-56015-1_230-1

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