Advertisement

Monoamine oxidase-B inhibitors in the treatment of Parkinson’s disease: clinical–pharmacological aspects

  • Peter Riederer
  • Thomas Müller
Neurology and Preclinical Neurological Studies - Review Article

Abstract

This invited narrative review emphasizes the role of MAO-B inhibition in the drug portfolio for dopamine substitution in patients with Parkinson’s disease. Neuronal and glial MAO-B inhibition contributes to more stable levels of dopamine and other biogenic amines in the synaptic cleft. Accordingly, symptomatic effects of MAO-B inhibition for a limited amelioration of impaired motor behaviour and wearing-off phenomena in patients with Parkinson’s disease are well proven, even when MAO-B inhibitors are only applied together with dopamine agonists. Delay of disease progression by MAO-B inhibition is under debate despite positive experimental findings. This discussion does not consider, that levodopa, respectively, dopamine agonists, are substrates, respectively, inhibitors of the ABCB1 (P-gp, MDR1, and CD243) transporter system. It supports toxin efflux over the blood–brain barrier. ABCB1 transporters have a limited capacity. MAO-B inhibitors do not weaken it. Treatment with MAO-B inhibitors is advantageous as it enables sparing of dopamine agonist and levodopa dosing.

Keywords

Monoamine oxidase Selegiline Rasagiline Safinamide ABCB1 transporter 

References

  1. Apetauerova D, Scala SA, Hamill RW, Simon DK, Pathak S, Ruthazer R, Standaert DG, Yacoubian TA (2016) CoQ10 in progressive supranuclear palsy: a randomized, placebo-controlled, double-blind trial. Neurol Neuroimmunol Neuroinflamm 3:e266CrossRefPubMedPubMedCentralGoogle Scholar
  2. Barone P, Fernandez HH, Ferreira J, Müller T, Saint-Hilaire M, Stacy M, Tolosa E, Anand R (2013) Safinamide as an add-on therapy to a stable dose of a single dopamine agonist: results from a randomized, placebo-controlled, 24-week multicenter trial in early idiopathic Parkinson disease (PD) patients (MOTION Study). Neurology 80:P01–P061Google Scholar
  3. Bartels AL, van Berckel BN, Lubberink M, Luurtsema G, Lammertsma AA, Leenders KL (2008a) Blood–brain barrier P-glycoprotein function is not impaired in early Parkinson’s disease. Parkinsonism Relat Disord 14:505–508CrossRefPubMedGoogle Scholar
  4. Bartels AL, Willemsen AT, Kortekaas R, de Jong BM, de Vries R, de Klerk O, van Oostrom JC, Portman A, Leenders KL (2008b) Decreased blood–brain barrier P-glycoprotein function in the progression of Parkinson’s disease, PSP and MSA. J Neural Transm 115:1001–1009CrossRefPubMedPubMedCentralGoogle Scholar
  5. Beal MF, Oakes D, Shoulson I, Henchcliffe C, Galpern WR, Haas R, Juncos JL, Nutt JG, Voss TS, Ravina B, Shults CM, Helles K, Snively V, Lew MF, Griebner B, Watts A, Gao S, Pourcher E, Bond L, Kompoliti K, Agarwal P, Sia C, Jog M, Cole L, Sultana M, Kurlan R, Richard I, Deeley C, Waters CH, Figueroa A, Arkun A, Brodsky M, Ondo WG, Hunter CB, Jimenez-Shahed J, Palao A, Miyasaki JM, So J, Tetrud J, Reys L, Smith K, Singer C, Blenke A, Russell DS, Cotto C, Friedman JH, Lannon M, Zhang L, Drasby E, Kumar R, Subramanian T, Ford DS, Grimes DA, Cote D, Conway J, Siderowf AD, Evatt ML, Sommerfeld B, Lieberman AN, Okun MS, Rodriguez RL, Merritt S, Swartz CL, Martin WR, King P, Stover N, Guthrie S, Watts RL, Ahmed A, Fernandez HH, Winters A, Mari Z, Dawson TM, Dunlop B, Feigin AS, Shannon B, Nirenberg MJ, Ogg M, Ellias SA, Thomas CA, Frei K, Bodis-Wollner I, Glazman S, Mayer T, Hauser RA, Pahwa R, Langhammer A, Ranawaya R, Derwent L, Sethi KD, Farrow B, Prakash R, Litvan I, Robinson A, Sahay A, Gartner M, Hinson VK, Markind S, Pelikan M, Perlmutter JS, Hartlein J, Molho E, Evans S, Adler CH, Duffy A, Lind M, Elmer L, Davis K, Spears J, Wilson S, Leehey MA, Hermanowicz N, Niswonger S, Shill HA, Obradov S, Rajput A, Cowper M, Lessig S, Song D, Fontaine D, Zadikoff C, Williams K, Blindauer KA, Bergholte J, Propsom CS, Stacy MA, Field J, Mihaila D, Chilton M, Uc EY, Sieren J, Simon DK, Kraics L, Silver A, Boyd JT, Hamill RW, Ingvoldstad C, Young J, Thomas K, Kostyk SK, Wojcieszek J, Pfeiffer RF, Panisset M, Beland M, Reich SG, Cines M, Zappala N, Rivest J, Zweig R, Lumina LP, Hilliard CL, Grill S, Kellermann M, Tuite P, Rolandelli S, Kang UJ, Young J, Rao J, Cook MM, Severt L, Boyar K (2014) A randomized clinical trial of high-dosage coenzyme Q10 in early Parkinson disease: no evidence of benefit. JAMA Neurol 71:543–552CrossRefPubMedGoogle Scholar
  6. Calzetti S, Negrotti A, Cassio A (1995) l-deprenyl as an adjunct to low-dose bromocriptine in early Parkinson’s disease: a short-term, double-blind, and prospective follow-up study. Clin Neuropharmacol 18:250–257CrossRefPubMedGoogle Scholar
  7. de Rijk MC, Launer LJ, Berger K, Breteler MM, Dartigues JF, Baldereschi M, Fratiglioni L, Lobo A, Martinez-Lage J, Trenkwalder C, Hofman A (2000) Prevalence of Parkinson’s disease in Europe: a collaborative study of population-based cohorts. Neurologic Diseases in the Elderly Research Group. Neurology 54:S21–S23PubMedGoogle Scholar
  8. Dutheil F, Beaune P, Tzourio C, Loriot MA, Elbaz A (2010) Interaction between ABCB1 and professional exposure to organochlorine insecticides in Parkinson disease. Arch Neurol 67:739–745CrossRefPubMedGoogle Scholar
  9. Ekesbo A, Rydin E, Torstenson R, Sydow O, Laengstrom B, Tedroff J (1999) Dopamine autoreceptor function is lost in advanced Parkinson’s disease. Neurology 52:120–125CrossRefPubMedGoogle Scholar
  10. Fuller RW, Clemens JA, Hynes MD III (1982) Degree of selectivity of pergolide as an agonist at presynaptic versus postsynaptic dopamine receptors: implications for prevention or treatment of tardive dyskinesia. J Clin Psychopharmacol 2:371–375CrossRefPubMedGoogle Scholar
  11. Garcia-Ruiz PJ, Martinez Castrillo JC, Alonso-Canovas A, Herranz BA, Vela L, Sanchez AP, Mata M, Olmedilla GN, Mahillo Fernandez I (2014) Impulse control disorder in patients with Parkinson’s disease under dopamine agonist therapy: a multicentre study. J Neurol Neurosurg Psychiatry 85:840–844CrossRefPubMedGoogle Scholar
  12. Götz ME, Gerstner A, Harth R, Dirr A, Janetzky B, Kuhn W, Riederer P, Gerlach M (2000) Altered redox state of platelet coenzyme Q10 in Parkinson’s disease. J Neural Transm 107:41–48CrossRefPubMedGoogle Scholar
  13. Gregory AM, Buysse DJ, Willis TA, Rijsdijk FV, Maughan B, Rowe R, Cartwright S, Barclay NL, Eley TC (2011) Associations between sleep quality and anxiety and depression symptoms in a sample of young adult twins and siblings. J Psychosom Res 71:250–255CrossRefPubMedGoogle Scholar
  14. Hauser RA, Silver D, Choudhry A, Eyal E, Isaacson S (2014) Randomized, controlled trial of rasagiline as an add-on to dopamine agonists in Parkinson’s disease. Mov Disord 29:1028–1034CrossRefPubMedGoogle Scholar
  15. Häussermann P, Kuhn W, Przuntek H, Müller T (2001) Integrity of the blood-cerebrospinal fluid barrier in early Parkinson’s disease. Neurosci Lett 300:182–184CrossRefPubMedGoogle Scholar
  16. Korchounov A, Winter Y, Rossy W (2012) Combined beneficial effect of rasagiline on motor function and depression in de novo PD. Clin Neuropharmacol 35:121–124CrossRefPubMedGoogle Scholar
  17. Kovacs N, Janszky J, Nagy F (2011) Cost effectiveness of rasagiline and pramipexole as treatment strategies in early Parkinson’s disease in the UK setting: an economic Markov model evaluation. Drugs Aging 28:161–162CrossRefPubMedGoogle Scholar
  18. Kronstrand R, Ahlner J, Dizdar N, Larson G (2003) Quantitative analysis of desmethylselegiline, methamphetamine, and amphetamine in hair and plasma from Parkinson patients on long-term selegiline medication. J Anal Toxicol 27:135–141CrossRefPubMedGoogle Scholar
  19. Laine K, Anttila M, Heinonen E, Helminen A, Huupponen R, Maki-Ikola O, Reinikainen K, Scheinin M (1997) Lack of adverse interactions between concomitantly administered selegiline and citalopram. Clin Neuropharmacol 20:419–433CrossRefPubMedGoogle Scholar
  20. Lecht S, Haroutiunian S, Hoffman A, Lazarovici P (2007) Rasagiline—a novel MAO B inhibitor in Parkinson’s disease therapy. Ther Clin Risk Manag 3:467–474PubMedPubMedCentralGoogle Scholar
  21. Mao A, Freeman KA, Tallarida RJ (1996) Transient loss of dopamine autoreceptor control in the presence of highly potent dopamine agonists. Life Sci 59:L317–L324CrossRefGoogle Scholar
  22. Mizuno Y, Hattori N, Kondo T, Nomoto M, Origasa H, Takahashi R, Yamamoto M, Yanagisawa N (2017) A Randomized double-blind placebo-controlled phase III trial of selegiline monotherapy for early Parkinson disease. Clin Neuropharmacol 40:201–207CrossRefPubMedPubMedCentralGoogle Scholar
  23. Muhlack S, Herrmann L, Salmen S, Müller T (2014) Fewer fluctuations, higher maximum concentration and better motor response of levodopa with catechol-O-methyltransferase inhibition. J Neural Transm 121:1357–1366CrossRefPubMedGoogle Scholar
  24. Müller T (2012) Drug therapy in patients with Parkinson’s disease. Transl Neurodegener 1:1–10CrossRefGoogle Scholar
  25. Müller T (2014) Pharmacokinetic/pharmacodynamic evaluation of rasagiline mesylate for Parkinson’s disease. Expert Opin Drug Metab Toxicol 10:1423–1432CrossRefPubMedGoogle Scholar
  26. Müller T, Foley P (2017) Clinical pharmacokinetics and pharmacodynamics of safinamide. Clin Pharmacokinet 56:251–261CrossRefPubMedGoogle Scholar
  27. Müller T, Eising EG, Reiners C, Przuntek H, Jacob M, Kuhn W (1997) 2-[123I]-iodolisuride SPET visualizes dopaminergic loss in de-novo parkinsonian patients: is it a marker of striatal pre-synaptic degeneration? Nucl Med Commun 18:1115–1121CrossRefPubMedGoogle Scholar
  28. Müller T, Hoffmann JA, Dimpfel W, Oehlwein C (2013) Switch from selegiline to rasagiline is beneficial in patients with Parkinson’s disease. J Neural Transm 120:761–765CrossRefPubMedGoogle Scholar
  29. Müller T, Öhm G, Eilert K, Möhr K, Rotter S, Haas T, Küchler M, Lütge S, Marg M, Rothe H (2017) Benefit on motor and non-motor behavior in a specialized unit for Parkinson’s disease. J Neural Transm 124:715–720CrossRefPubMedGoogle Scholar
  30. Nappi G, Martignoni E, Horowski R, Pacchetti C, Rainer E, Bruggi P, Runge I (1991) Lisuride plus selegiline in the treatment of early Parkinson’s disease. Acta Neurol Scand 83:407–410CrossRefPubMedGoogle Scholar
  31. Olanow CW, Rascol O, Hauser R, Feigin PD, Jankovic J, Lang A, Langston W, Melamed E, Poewe W, Stocchi F, Tolosa E (2009) A double-blind, delayed-start trial of rasagiline in Parkinson’s disease. N Engl J Med 361:1268–1278CrossRefPubMedGoogle Scholar
  32. Parkinson Study Group (1996) Impact of deprenyl and tocopherol treatment on Parkinson’s disease in DATATOP patients requiring levodopa. Ann Neurol 39:37–45CrossRefGoogle Scholar
  33. Pilleri M, Antonini A (2014) Novel levodopa formulations in the treatment of Parkinson’s disease. Expert Rev Neurother 14:143–149CrossRefPubMedGoogle Scholar
  34. Pingili R, Vemulapalli S, Mullapudi SS, Nuthakki S, Pendyala S, Kilaru N (2016) Pharmacokinetic interaction study between flavanones (hesperetin, naringenin) and rasagiline mesylate in wistar rats. Drug Dev Ind Pharm 42:1110–1117CrossRefPubMedGoogle Scholar
  35. Przuntek H, Conrad B, Dichgans J, Kraus PH, Krauseneck P, Pergande G, Rinne U, Schimrigk K, Schnitker J, Vogel HP (1999) SELEDO: a 5-year long-term trial on the effect of selegiline in early Parkinsonian patients treated with levodopa. Eur J Neurol 6:141–150CrossRefPubMedGoogle Scholar
  36. Przuntek H, Bittkau S, Bliesath H, Buttner U, Fuchs G, Glass J, Haller H, Klockgether T, Kraus P, Lachenmayer L, Müller D, Müller T, Rathay B, Sgonina J, Steinijans V, Teshmar E, Ulm G, Volc D (2002) Budipine provides additional benefit in patients with Parkinson disease receiving a stable optimum dopaminergic drug regimen. Arch Neurol 59:803–806CrossRefPubMedGoogle Scholar
  37. Przuntek H, Müller T, Riederer P (2004) Diagnostic staging of Parkinson’s disease: conceptual aspects. J Neural Transm 111:201–216CrossRefPubMedGoogle Scholar
  38. Rajput AH, Birdi S (1997) Epidemiology of Parkinson’s disease. Parkinsonism Relat Disord 3:175–186CrossRefPubMedGoogle Scholar
  39. Rascol O, Hauser RA, Stocchi F, Fitzer-Attas CJ, Sidi Y, Abler V, Olanow CW, Investigators AFU (2016) Long-term effects of rasagiline and the natural history of treated Parkinson’s disease. Mov Disord 31:1489–1496CrossRefPubMedGoogle Scholar
  40. Reynolds GP, Riederer P, Sandler M, Jellinger K, Seeman D (1978) Amphetamine and 2-phenylethylamine in post-mortem Parkinsonian brain after (-)deprenyl administration. J Neural Transm 43:271–277CrossRefPubMedGoogle Scholar
  41. Riederer P, Jellinger K, Danielczyk W, Seemann D, Ulm G, Reynolds GP, Birkmayer W, Koppel H (1983) Combination treatment with selective monoamine oxidase inhibitors and dopaminergic agonists in Parkinson’s disease: biochemical and clinical observations. Adv Neural 37:159–176Google Scholar
  42. Schapira AH, McDermott MP, Barone P, Comella CL, Albrecht S, Hsu HH, Massey DH, Mizuno Y, Poewe W, Rascol O, Marek K (2013) Pramipexole in patients with early Parkinson’s disease (PROUD): a randomised delayed-start trial. Lancet Neurol 12:747–755CrossRefPubMedPubMedCentralGoogle Scholar
  43. Sian-Hülsmann J, Mandel S, Youdim MB, Riederer P (2011) The relevance of iron in the pathogenesis of Parkinson’s disease. J Neurochem 118:939–957CrossRefPubMedGoogle Scholar
  44. Sian-Hülsmann J, Monoranu C, Strobel S, Riederer P (2015) Lewy bodies: a spectator or salient killer? CNS Neurol Disord Drug Targets 14:947–955CrossRefPubMedGoogle Scholar
  45. Szökő E, Tábi T, Riederer P, Vécsei L, Magyar K (2018) Pharmacological aspects of the neuroprotective effects of irreversible MAO-B inhibitors, selegiline and rasagiline, in Parkinson’s disease. J Neural Transm (Vienna).  https://doi.org/10.1007/s00702-018-1853-9
  46. Tanner CM, Ross GW, Jewell SA, Hauser RA, Jankovic J, Factor SA, Bressman S, Deligtisch A, Marras C, Lyons KE, Bhudhikanok GS, Roucoux DF, Meng C, Abbott RD, Langston JW (2009) Occupation and risk of parkinsonism: a multicenter case-control study. Arch Neurol 66:1106–1113CrossRefPubMedGoogle Scholar
  47. Taylor DJ (2008) Insomnia and depression. Sleep 31:447–448CrossRefPubMedPubMedCentralGoogle Scholar
  48. Thorpy M (2007) Therapeutic advances in narcolepsy. Sleep Med 8:427–440CrossRefPubMedGoogle Scholar
  49. Vautier S, Fernandez C (2009) ABCB1: the role in Parkinson’s disease and pharmacokinetics of antiparkinsonian drugs. Expert Opin Drug Metab Toxicol 5:1349–1358CrossRefPubMedGoogle Scholar
  50. Vautier S, Milane A, Fernandez C, Buyse M, Chacun H, Farinotti R (2008) Interactions between antiparkinsonian drugs and ABCB1/P-glycoprotein at the blood–brain barrier in a rat brain endothelial cell model. Neurosci Lett 442:19–23CrossRefPubMedGoogle Scholar
  51. Yoritaka A, Kawajiri S, Yamamoto Y, Nakahara T, Ando M, Hashimoto K, Nagase M, Saito Y, Hattori N (2015) Randomized, double-blind, placebo-controlled pilot trial of reduced coenzyme Q10 for Parkinson’s disease. Parkinsonism Relat Disord 21:911–916CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Center of Mental Health, Department of Psychiatry, Psychosomatics and PsychotherapyUniversity Hospital WürzburgWürzburgGermany
  2. 2.Department of NeurologySt. Joseph Hospital Berlin-WeißenseeBerlinGermany

Personalised recommendations