Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Neurology
Published in: BMC Neurology 1/2011

Open Access 01-12-2011 | Debate

Controversies in Neurology: why monoamine oxidase B inhibitors could be a good choice for the initial treatment of Parkinson's disease

Authors: Matthias Löhle, Heinz Reichmann

Published in: BMC Neurology | Issue 1/2011

Login to get access

Abstract

Background

Early initiation of pharmacotherapy in Parkinson's disease (PD) is nowadays widely advocated by experts since the delay of treatment has shown to be associated with a significant deterioration of health related quality of life in affected patients. Due to marked advances in PD treatment during the last decades, physicians are nowadays fortunately equipped with a variety of substances that can effectively ameliorate emerging motor symptoms of the disease, among them levodopa, dopamine agonists and monoamine oxidase type B (MAO-B) inhibitors. Despite numerous drug intervention trials in early PD, there is however still ongoing controversy among neurologists which substance to use for the initial treatment of the disease.

Discussion

In multiple studies, MAO-B inhibitors, such as selegiline and rasagiline, have shown to provide mild symptomatic effects, delay the need for levodopa, and to reduce the incidence of motor fluctuations. Although their symptomatic efficacy is inferior compared to dopamine agonists and levodopa, MAO-B inhibitors undoubtedly have fewer side effects and are easy to administer. In contrary to their competitors, MAO-B inhibitors may furthermore offer a chance for disease modification, which so far remains a major unmet need in the management of PD and eventually makes them ideal candidates for the early treatment of the disease.

Summary

MAO-B inhibitors may constitute a preferable therapeutic option for early PD, mainly due to their favourable safety profile and their putative neuroprotective capabilities. Since the symptomatic effects of MAO-B inhibitors are comparatively mild, dopamine agonists and levodopa should however be considered for initial treatment in those PD patients, in whom robust and immediate symptomatic relief needs to be prioritized.
Literature
1.
Alves G, Forsaa EB, Pedersen KF, Dreetz Gjerstad M, Larsen JP: Epidemiology of Parkinson's disease. J Neurol. 2008, 255 (Suppl 5): 18-32.CrossRefPubMed
2.
Grosset D, Taurah L, Burn DJ, MacMahon D, Forbes A, Turner K, Bowron A, Walker R, Findley L, Foster O, et al: A multicentre longitudinal observational study of changes in self reported health status in people with Parkinson's disease left untreated at diagnosis. J Neurol Neurosurg Psychiatry. 2007, 78 (5): 465-469.CrossRefPubMed
3.
Schapira AH, Obeso J: Timing of treatment initiation in Parkinson's disease: a need for reappraisal?. Ann Neurol. 2006, 59 (3): 559-562. 10.1002/ana.20789.CrossRefPubMed
4.
Parkinson Study Group: Effects of tocopherol and deprenyl on the progression of disability in early Parkinson's disease. N Engl J Med. 1993, 328 (3): 176-183.CrossRef
5.
Parkinson Study Group: A controlled trial of rasagiline in early Parkinson disease: the TEMPO Study. Arch Neurol. 2002, 59 (12): 1937-1943. 10.1001/archneur.59.12.1937.CrossRef
6.
Parkinson Study Group: A controlled, randomized, delayed-start study of rasagiline in early Parkinson disease. Arch Neurol. 2004, 61 (4): 561-566. 10.1001/archneur.61.4.561.CrossRef
7.
Olanow CW, Rascol O, Hauser R, Feigin PD, Jankovic J, Lang A, Langston W, Melamed E, Poewe W, Stocchi F, et al: A double-blind, delayed-start trial of rasagiline in Parkinson's disease. N Engl J Med. 2009, 361 (13): 1268-1278. 10.1056/NEJMoa0809335.CrossRefPubMed
8.
Allain H, Pollak P, Neukirch HC: Symptomatic effect of selegiline in de novo Parkinsonian patients. The French Selegiline Multicenter Trial. Mov Disord. 1993, 8 (Suppl 1): S36-40.CrossRefPubMed
9.
Palhagen S, Heinonen EH, Hagglund J, Kaugesaar T, Kontants H, Maki-Ikola O, Palm R, Turunen J: Selegiline delays the onset of disability in de novo parkinsonian patients. Swedish Parkinson Study Group. Neurology. 1998, 51 (2): 520-525.CrossRefPubMed
10.
Schrag A, Sampaio C, Counsell N, Poewe W: Minimal clinically important change on the unified Parkinson's disease rating scale. Mov Disord. 2006, 21 (8): 1200-1207. 10.1002/mds.20914.CrossRefPubMed
11.
Parkinson Study Group: Safety and efficacy of pramipexole in early Parkinson disease. A randomized dose-ranging study. Jama. 1997, 278 (2): 125-130.CrossRef
12.
Adler CH, Sethi KD, Hauser RA, Davis TL, Hammerstad JP, Bertoni J, Taylor RL, Sanchez-Ramos J, O'Brien CF: Ropinirole for the treatment of early Parkinson's disease. The Ropinirole Study Group. Neurology. 1997, 49 (2): 393-399.CrossRefPubMed
13.
Shannon KM, Bennett JP, Friedman JH: Efficacy of pramipexole, a novel dopamine agonist, as monotherapy in mild to moderate Parkinson's disease. The Pramipexole Study Group. Neurology. 1997, 49 (3): 724-728.CrossRefPubMed
14.
Parkinson Study Group: A controlled trial of rotigotine monotherapy in early Parkinson's disease. Arch Neurol. 2003, 60 (12): 1721-1728. 10.1001/archneur.60.12.1721.CrossRef
15.
Fahn S, Oakes D, Shoulson I, Kieburtz K, Rudolph A, Lang A, Olanow CW, Tanner C, Marek K: Levodopa and the progression of Parkinson's disease. N Engl J Med. 2004, 351 (24): 2498-2508.CrossRefPubMed
16.
Hauser RA, Auinger P, Oakes D: Levodopa response in early Parkinson's disease. Mov Disord. 2009, 24 (16): 2328-2336.PubMed
17.
Parkinson Study Group: Effect of lazabemide on the progression of disability in early Parkinson's disease. Ann Neurol. 1996, 40 (1): 99-107. 10.1002/ana.410400116.CrossRef
18.
Tetrud JW, Langston JW: The effect of deprenyl (selegiline) on the natural history of Parkinson's disease. Science. 1989, 245 (4917): 519-522. 10.1126/science.2502843.CrossRefPubMed
19.
Myllyla VV, Sotaniemi KA, Vuorinen JA, Heinonen EH: Selegiline as initial treatment in de novo parkinsonian patients. Neurology. 1992, 42 (2): 339-343.CrossRefPubMed
20.
Ives NJ, Stowe RL, Marro J, Counsell C, Macleod A, Clarke CE, Gray R, Wheatley K: Monoamine oxidase type B inhibitors in early Parkinson's disease: meta-analysis of 17 randomised trials involving 3525 patients. BMJ. 2004, 329 (7466): 593-10.1136/bmj.38184.606169.AE.CrossRefPubMedPubMedCentral
21.
Myllyla VV, Sotaniemi KA, Hakulinen P, Maki-Ikola O, Heinonen EH: Selegiline as the primary treatment of Parkinson's disease--a long-term double-blind study. Acta Neurol Scand. 1997, 95 (4): 211-218. 10.1111/j.1600-0404.1997.tb00101.x.CrossRefPubMed
22.
Caraceni T, Musicco M: Levodopa or dopamine agonists, or deprenyl as initial treatment for Parkinson's disease. A randomized multicenter study. Parkinsonism Relat Disord. 2001, 7 (2): 107-114. 10.1016/S1353-8020(00)00023-7.CrossRefPubMed
23.
Rascol O, Brooks DJ, Korczyn AD, De DPP, Clarke CE, Lang AE: A five-year study of the incidence of dyskinesia in patients with early Parkinson's disease who were treated with ropinirole or levodopa. N Engl J Med. 2000, 342: 1484-1491. 10.1056/NEJM200005183422004.CrossRefPubMed
24.
Parkinson Study Group CALM Cohort Investigators: Long-term effect of initiating pramipexole vs levodopa in early Parkinson disease. Arch Neurol. 2009, 66 (5): 563-570.CrossRef
25.
Holloway RG, Shoulson I, Fahn S, Kieburtz K, Lang A, Marek K, McDermott M, Seibyl J, Weiner W, Musch B, et al: Pramipexole vs levodopa as initial treatment for Parkinson disease: a 4-year randomized controlled trial. Arch Neurol. 2004, 61 (7): 1044-1053.PubMed
26.
Poewe WH, Lees AJ, Stern GM: Low-dose L-dopa therapy in Parkinson's disease: a 6-year follow-up study. Neurology. 1986, 36 (11): 1528-1530.CrossRefPubMed
27.
Martin WR, Sloan JW, Sapira JD, Jasinski DR: Physiologic, subjective, and behavioral effects of amphetamine, methamphetamine, ephedrine, phenmetrazine, and methylphenidate in man. Clin Pharmacol Ther. 1971, 12 (2): 245-258.CrossRefPubMed
28.
Churchyard A, Mathias CJ, Boonkongchuen P, Lees AJ: Autonomic effects of selegiline: possible cardiovascular toxicity in Parkinson's disease. J Neurol Neurosurg Psychiatry. 1997, 63 (2): 228-234. 10.1136/jnnp.63.2.228.CrossRefPubMedPubMedCentral
29.
Yasar S, Goldberg JP, Goldberg SR: Are metabolites of l-deprenyl (selegiline) useful or harmful? Indications from preclinical research. J Neural Transm Suppl. 1996, 48: 61-73.PubMed
30.
Yasar S, Justinova Z, Lee SH, Stefanski R, Goldberg SR, Tanda G: Metabolic transformation plays a primary role in the psychostimulant-like discriminative-stimulus effects of selegiline [(R)-(-)-deprenyl]. J Pharmacol Exp Ther. 2006, 317 (1): 387-394.CrossRefPubMed
31.
Gill JR, Masson DT, Bartter FC: Effects of hydroxyamphetamine (paredrine) on the function of the sympathetic nervous system in normotensive subjects. J Pharmacol Exp Ther. 1967, 155 (2): 288-295.PubMed
32.
Schulz R, Antonin KH, Hoffmann E, Jedrychowski M, Nilsson E, Schick C, Bieck PR: Tyramine kinetics and pressor sensitivity during monoamine oxidase inhibition by selegiline. Clin Pharmacol Ther. 1989, 46 (5): 528-536. 10.1038/clpt.1989.181.CrossRefPubMed
33.
Mantle TJ, Tipton KF, Garrett NJ: Inhibition of monoamine oxidase by amphetamine and related compounds. Biochem Pharmacol. 1976, 25 (18): 2073-2077. 10.1016/0006-2952(76)90432-9.CrossRefPubMed
34.
Suzuki O, Hattori H, Asano M, Oya M, Katsumata Y: Inhibition of monoamine oxidase by d-methamphetamine. Biochem Pharmacol. 1980, 29 (14): 2071-2073. 10.1016/0006-2952(80)90493-1.CrossRefPubMed
35.
Chen JJ, Swope DM, Dashtipour K: Comprehensive review of rasagiline, a second-generation monoamine oxidase inhibitor, for the treatment of Parkinson's disease. Clin Ther. 2007, 29 (9): 1825-1849. 10.1016/j.clinthera.2007.09.021.CrossRefPubMed
36.
Lees AJ: Comparison of therapeutic effects and mortality data of levodopa and levodopa combined with selegiline in patients with early, mild Parkinson's disease. Parkinson's Disease Research Group of the United Kingdom. BMJ. 1995, 311 (7020): 1602-1607.CrossRefPubMedPubMedCentral
37.
Ben-Shlomo Y, Churchyard A, Head J, Hurwitz B, Overstall P, Ockelford J, Lees AJ: Investigation by Parkinson's Disease Research Group of United Kingdom into excess mortality seen with combined levodopa and selegiline treatment in patients with early, mild Parkinson's disease: further results of randomised trial and confidential inquiry. BMJ. 1998, 316 (7139): 1191-1196.CrossRefPubMedPubMedCentral
38.
Löhle M, Storch A: Orally disintegrating selegiline for the treatment of Parkinson's disease. Expert Opin Pharmacother. 2008, 9 (16): 2881-2891. 10.1517/14656566.9.16.2881.CrossRefPubMed
39.
Rascol O, Brooks DJ, Melamed E, Oertel W, Poewe W, Stocchi F, Tolosa E: Rasagiline as an adjunct to levodopa in patients with Parkinson's disease and motor fluctuations (LARGO, Lasting effect in Adjunct therapy with Rasagiline Given Once daily, study): a randomised, double-blind, parallel-group trial. Lancet. 2005, 365 (9463): 947-954. 10.1016/S0140-6736(05)71083-7.CrossRefPubMed
40.
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. 2005, 62 (2): 241-248.CrossRef
41.
Goren T, Adar L, Sasson N, Weiss YM: Clinical pharmacology tyramine challenge study to determine the selectivity of the monoamine oxidase type B (MAO-B) inhibitor rasagiline. J Clin Pharmacol. 2010, 50 (12): 1420-1428. 10.1177/0091270010369674.CrossRefPubMed
42.
Perez-Lloret S, Rascol O: Safety of rasagiline for the treatment of Parkinson's disease. Expert Opin Drug Saf. 2011, 10 (4): 633-643. 10.1517/14740338.2011.573784.CrossRefPubMed
43.
Richard IH, Kurlan R, Tanner C, Factor S, Hubble J, Suchowersky O, Waters C: Serotonin syndrome and the combined use of deprenyl and an antidepressant in Parkinson's disease. Parkinson Study Group. Neurology. 1997, 48 (4): 1070-1077.CrossRefPubMed
44.
Leopold NA, Polansky M, Hurka MR: Drug adherence in Parkinson's disease. Mov Disord. 2004, 19 (5): 513-517. 10.1002/mds.20041.CrossRefPubMed
45.
Grosset KA, Bone I, Grosset DG: Suboptimal medication adherence in Parkinson's disease. Mov Disord. 2005, 20 (11): 1502-1507. 10.1002/mds.20602.CrossRefPubMed
46.
Grosset D, Antonini A, Canesi M, Pezzoli G, Lees A, Shaw K, Cubo E, Martinez-Martin P, Rascol O, Negre-Pages L, et al: Adherence to antiparkinson medication in a multicenter European study. Mov Disord. 2009, 24 (6): 826-832. 10.1002/mds.22112.CrossRefPubMed
47.
Stocchi F: The hypothesis of the genesis of motor complications and continuous dopaminergic stimulation in the treatment of Parkinson's disease. Parkinsonism Relat Disord. 2009, 15 (Suppl 1): S9-S15.CrossRefPubMed
48.
Nilsson H, Ekberg O, Olsson R, Hindfelt B: Quantitative assessment of oral and pharyngeal function in Parkinson's disease. Dysphagia. 1996, 11 (2): 144-150. 10.1007/BF00417905.CrossRefPubMed
49.
Potulska A, Friedman A, Krolicki L, Spychala A: Swallowing disorders in Parkinson's disease. Parkinsonism Relat Disord. 2003, 9 (6): 349-353. 10.1016/S1353-8020(03)00045-2.CrossRefPubMed
50.
Virely P, Yarwood R: Zydis: a novel, fast dissolving dosage form. Manuf Chem. 1990, 36-37. 61
51.
Clarke A, Johnson ES, Mallard N, Corn TH, Johnston A, Boyce M, Warrington S, MacMahon DG: A new low-dose formulation of selegiline: clinical efficacy, patient preference and selectivity for MAO-B inhibition. J Neural Transm. 2003, 110 (11): 1257-1271. 10.1007/s00702-003-0042-6.CrossRefPubMed
52.
Löhle M, Reichmann H: Clinical neuroprotection in Parkinson's disease - still waiting for the breakthrough. J Neurol Sci. 2010, 289 (1-2): 104-114. 10.1016/j.jns.2009.08.025.CrossRefPubMed
53.
Hely MA, Morris JG, Reid WG, Trafficante R: Sydney Multicenter Study of Parkinson's disease: non-L-dopa-responsive problems dominate at 15 years. Mov Disord. 2005, 20 (2): 190-199. 10.1002/mds.20324.CrossRefPubMed
54.
Olanow CW: The scientific basis for the current treatment of Parkinson's disease. Annu Rev Med. 2004, 55: 41-60. 10.1146/annurev.med.55.091902.104422.CrossRefPubMed
55.
Cohen G, Pasik P, Cohen B, Leist A, Mytilineou C, Yahr MD: Pargyline and deprenyl prevent the neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in monkeys. Eur J Pharmacol. 1984, 106 (1): 209-210. 10.1016/0014-2999(84)90700-3.CrossRefPubMed
56.
Heikkila RE, Manzino L, Cabbat FS, Duvoisin RC: Protection against the dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine by monoamine oxidase inhibitors. Nature. 1984, 311 (5985): 467-469. 10.1038/311467a0.CrossRefPubMed
57.
Mytilineou C, Radcliffe P, Leonardi EK, Werner P, Olanow CW: L-deprenyl protects mesencephalic dopamine neurons from glutamate receptor-mediated toxicity in vitro. J Neurochem. 1997, 68 (1): 33-39.CrossRefPubMed
58.
Mytilineou C, Radcliffe PM, Olanow CW: L-(-)-desmethylselegiline, a metabolite of selegiline [L-(-)-deprenyl], protects mesencephalic dopamine neurons from excitotoxicity in vitro. J Neurochem. 1997, 68 (1): 434-436.CrossRefPubMed
59.
Mytilineou C, Leonardi EK, Radcliffe P, Heinonen EH, Han SK, Werner P, Cohen G, Olanow CW: Deprenyl and desmethylselegiline protect mesencephalic neurons from toxicity induced by glutathione depletion. J Pharmacol Exp Ther. 1998, 284 (2): 700-706.PubMed
60.
Finberg JP, Takeshima T, Johnston JM, Commissiong JW: Increased survival of dopaminergic neurons by rasagiline, a monoamine oxidase B inhibitor. Neuroreport. 1998, 9 (4): 703-707. 10.1097/00001756-199803090-00026.CrossRefPubMed
61.
Goggi J, Theofilopoulos S, Riaz SS, Jauniaux E, Stern GM, Bradford HF: The neuronal survival effects of rasagiline and deprenyl on fetal human and rat ventral mesencephalic neurones in culture. Neuroreport. 2000, 11 (18): 3937-3941. 10.1097/00001756-200012180-00007.CrossRefPubMed
62.
Maruyama W, Akao Y, Youdim MB, Naoi M: Neurotoxins induce apoptosis in dopamine neurons: protection by N-propargylamine-1(R)- and (S)-aminoindan, rasagiline and TV1022. J Neural Transm Suppl. 2000, 171-186. 60
63.
Naoi M, Maruyama W, Youdim MB, Yu P, Boulton AA: Anti-apoptotic function of propargylamine inhibitors of type-B monoamine oxidase. Inflammopharmacology. 2003, 11 (2): 175-181. 10.1163/156856003765764344.CrossRefPubMed
64.
Blandini F, Armentero MT, Fancellu R, Blaugrund E, Nappi G: Neuroprotective effect of rasagiline in a rodent model of Parkinson's disease. Exp Neurol. 2004, 187 (2): 455-459. 10.1016/j.expneurol.2004.03.005.CrossRefPubMed
65.
Kupsch A, Sautter J, Gotz ME, Breithaupt W, Schwarz J, Youdim MB, Riederer P, Gerlach M, Oertel WH: Monoamine oxidase-inhibition and MPTP-induced neurotoxicity in the non-human primate: comparison of rasagiline (TVP 1012) with selegiline. J Neural Transm. 2001, 108 (8-9): 985-1009.CrossRefPubMed
66.
Parkinson Study Group: Effect of deprenyl on the progression of disability in early Parkinson's disease. N Engl J Med. 1989, 321 (20): 1364-1371.CrossRef
67.
Parkinson Study Group: Mortality in DATATOP: a multicenter trial in early Parkinson's disease. Ann Neurol. 1998, 43 (3): 318-325. 10.1002/ana.410430309.CrossRef
68.
Hauser RA, Lew MF, Hurtig HI, Ondo WG, Wojcieszek J, Fitzer-Attas CJ: Long-term outcome of early versus delayed rasagiline treatment in early Parkinson's disease. Mov Disord. 2009, 24 (4): 564-573. 10.1002/mds.22402.CrossRefPubMed
69.
Clarke CE: Are delayed-start design trials to show neuroprotection in Parkinson's disease fundamentally flawed?. Mov Disord. 2008, 23 (6): 784-789. 10.1002/mds.21918.CrossRefPubMed
70.
Parkinson SG: Dopamine transporter brain imaging to assess the effects of pramipexole vs levodopa on Parkinson disease progression. Jama. 2002, 287 (13): 1653-1661. 10.1001/jama.287.13.1653.CrossRef
71.
Whone AL, Watts RL, Stoessl AJ, Davis M, Reske S, Nahmias C, Lang AE, Rascol O, Ribeiro MJ, Remy P, et al: Slower progression of Parkinson's disease with ropinirole versus levodopa: The REAL-PET study. Ann Neurol. 2003, 54 (1): 93-101. 10.1002/ana.10609.CrossRefPubMed
72.
Ravina B, Eidelberg D, Ahlskog JE, Albin RL, Brooks DJ, Carbon M, Dhawan V, Feigin A, Fahn S, Guttman M, et al: The role of radiotracer imaging in Parkinson disease. Neurology. 2005, 64: 208-215. 10.1212/01.WNL.0000149403.14458.7F.CrossRefPubMed
Metadata
Title
Controversies in Neurology: why monoamine oxidase B inhibitors could be a good choice for the initial treatment of Parkinson's disease
Authors
Matthias Löhle
Heinz Reichmann
Publication date
01-12-2011
Publisher
BioMed Central
Published in
BMC Neurology / Issue 1/2011
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/1471-2377-11-112

Other articles of this Issue 1/2011

BMC Neurology 1/2011 Go to the issue

Research article

Cognitive function and quality of life in multiple sclerosis patients: a cross-sectional study

Research article

Gender-dependence of substituted judgment on quality of life in patients with dementia

Research article

Refractory migraine in a headache clinic population

Research article

Environmental factors in early childhood are associated with multiple sclerosis: a case-control study

Case report

Stuttered swallowing: Electric stimulation of the right insula interferes with water swallowing. A case report

Debate

Pros and cons of a prion-like pathogenesis in Parkinson's disease