Skip to main content
Top
Published in: CNS Drugs 12/2011

01-12-2011 | Review Article

Monoamine Oxidase B Inhibitors for the Treatment of Parkinson’s Disease

A Review of Symptomatic and Potential Disease-Modifying Effects

Author: Prof. Anthony H. V. Schapira

Published in: CNS Drugs | Issue 12/2011

Login to get access

Abstract

Parkinson’s disease is a disorder characterized pathologically by progressive neurodegeneration of the dopaminergic cells of the nigrostriatal pathway. Although the resulting dopamine deficiency is the cause of the typical motor features of Parkinson’s disease (bradykinesia, rigidity, tremor), additional non-motor symptoms appear at various timepoints and are the result of non-dopamine nerve degeneration. Monoamine oxidase B (MAO-B) inhibitors are used in the symptomatic treatment of Parkinson’s disease as they increase synaptic dopamine by blocking its degradation. Two MAO-B inhibitors, selegiline and rasagiline, are currently licensed in Europe and North America for the symptomatic improvement of early Parkinson’s disease and to reduce off-time in patients with more advanced Parkinson’s disease and motor fluctuations related to levodopa. A third MAO-B inhibitor (safinamide), which also combines additional non-dopaminergic properties of potential benefit to Parkinson’s disease, is currently under development in phase III clinical trials as adjuvant therapy to either a dopamine agonist or levodopa.
MAO-B inhibitors have also been studied extensively for possible neuroprotective or disease-modifying actions. There is considerable laboratory evidence that MAO-B inhibitors do exert some neuroprotective properties, at least in the Parkinson’s disease models currently available. However, these models have significant limitations and caution is required in assuming that such results may easily be extrapolated to clinical trials. Rasagiline 1 mg/day has been shown to provide improved motor control in terms of Unified Parkinson’s Disease Rating Scale (UPDRS) score at 18 months in those patients with early disease who began the drug 9 months before a second group. There are a number of possible explanations for this effect that may include a disease-modifying action; however, the US FDA recently declined an application for the licence of rasagiline to be extended to cover disease modification.
Literature
1.
go back to reference Schapira AH, Olanow CW. Drug selection and timing of initiation of treatment in early Parkinson’s disease. Ann Neurol 2008 Dec; 64 Suppl. 2: S47–55PubMedCrossRef Schapira AH, Olanow CW. Drug selection and timing of initiation of treatment in early Parkinson’s disease. Ann Neurol 2008 Dec; 64 Suppl. 2: S47–55PubMedCrossRef
2.
go back to reference Birkmayer W, Riederer P, Youdim MB, et al. The potentiation of the anti akinetic effect after L-dopa treatment by an inhibitor of MAO-B, Deprenil. J Neural Transm 1975; 36(3–4): 303–26PubMedCrossRef Birkmayer W, Riederer P, Youdim MB, et al. The potentiation of the anti akinetic effect after L-dopa treatment by an inhibitor of MAO-B, Deprenil. J Neural Transm 1975; 36(3–4): 303–26PubMedCrossRef
3.
go back to reference Birkmayer W, Riederer P, Ambrozi L, et al. Implications of combined treatment with ‘Madopar’ and L-deprenil in Parkinson’s disease: a long-term study. Lancet 1977 Feb 26; 1(8009): 439–43PubMedCrossRef Birkmayer W, Riederer P, Ambrozi L, et al. Implications of combined treatment with ‘Madopar’ and L-deprenil in Parkinson’s disease: a long-term study. Lancet 1977 Feb 26; 1(8009): 439–43PubMedCrossRef
4.
go back to reference Lees AJ, Shaw KM, Kohout LJ, et al. Deprenyl in Parkinson’s disease. Lancet 1977 Oct 15; 2(8042): 791–5PubMedCrossRef Lees AJ, Shaw KM, Kohout LJ, et al. Deprenyl in Parkinson’s disease. Lancet 1977 Oct 15; 2(8042): 791–5PubMedCrossRef
5.
6.
go back to reference Schapira AH. Safinamide in the treatment of Parkinson’s disease. Expert Opin Pharmacother 2010 Sep; 11(13): 2261–8PubMedCrossRef Schapira AH. Safinamide in the treatment of Parkinson’s disease. Expert Opin Pharmacother 2010 Sep; 11(13): 2261–8PubMedCrossRef
7.
go back to reference The Parkinson Study Group. Effect of lazabemide on the progression of disability in early Parkinson’s disease. Ann Neurol 1996 Jul; 40(1): 99–107CrossRef The Parkinson Study Group. Effect of lazabemide on the progression of disability in early Parkinson’s disease. Ann Neurol 1996 Jul; 40(1): 99–107CrossRef
8.
go back to reference Kamada T, Chow T, Hiroi T, et al. Metabolism of selegiline hydrochloride, a selective monoamine b-type inhibitor, in human liver microsomes. Drug Metab Pharmacokinet 2002; 17(3): 199–206PubMedCrossRef Kamada T, Chow T, Hiroi T, et al. Metabolism of selegiline hydrochloride, a selective monoamine b-type inhibitor, in human liver microsomes. Drug Metab Pharmacokinet 2002; 17(3): 199–206PubMedCrossRef
9.
go back to reference Mandel S, Weinreb O, Amit T, et al. Mechanism of neuroprotective action of the anti-Parkinson drug rasagiline and its derivatives. Brain Res Brain Res Rev 2005 Apr; 48(2): 379–87PubMedCrossRef Mandel S, Weinreb O, Amit T, et al. Mechanism of neuroprotective action of the anti-Parkinson drug rasagiline and its derivatives. Brain Res Brain Res Rev 2005 Apr; 48(2): 379–87PubMedCrossRef
10.
go back to reference Bar AO, Amit T, Youdim MB. Contrasting neuroprotective and neurotoxic actions of respective metabolites of anti-Parkinson drugs rasagiline and selegiline. Neurosci Lett 2004 Jan 30; 355(3): 169–72CrossRef Bar AO, Amit T, Youdim MB. Contrasting neuroprotective and neurotoxic actions of respective metabolites of anti-Parkinson drugs rasagiline and selegiline. Neurosci Lett 2004 Jan 30; 355(3): 169–72CrossRef
11.
go back to reference Youdim MB, Gross A, Finberg JP. Rasagiline [N-propargyl-1R(+)-aminoindan], a selective and potent inhibitor of mitochondrial monoamine oxidase B. Br J Pharmacol 2001 Jan; 132(2): 500–6PubMedCrossRef Youdim MB, Gross A, Finberg JP. Rasagiline [N-propargyl-1R(+)-aminoindan], a selective and potent inhibitor of mitochondrial monoamine oxidase B. Br J Pharmacol 2001 Jan; 132(2): 500–6PubMedCrossRef
12.
go back to reference Chen JJ, Swope DM. Clinical pharmacology of rasagiline: a novel, second-generation propargylamine for the treatment of Parkinson disease. J Clin Pharmacol 2005 Aug; 45(8): 878–94PubMedCrossRef Chen JJ, Swope DM. Clinical pharmacology of rasagiline: a novel, second-generation propargylamine for the treatment of Parkinson disease. J Clin Pharmacol 2005 Aug; 45(8): 878–94PubMedCrossRef
13.
go back to reference Youdim MB, Amit T, Bar-Am O, et al. Amyloid processing and signal transduction properties of antiparkinson-antialzheimer neuroprotective drugs rasagiline and TV3326. Ann N Y Acad Sci 2003 May; 993: 378–86PubMedCrossRef Youdim MB, Amit T, Bar-Am O, et al. Amyloid processing and signal transduction properties of antiparkinson-antialzheimer neuroprotective drugs rasagiline and TV3326. Ann N Y Acad Sci 2003 May; 993: 378–86PubMedCrossRef
14.
go back to reference Binda C, Wang J, Pisani L, et al. Structures of human monoamine oxidase B complexes with selective noncovalent inhibitors: safinamide and coumarin analogs. J Med Chem 2007 Nov 15; 50(23): 5848–52PubMedCrossRef Binda C, Wang J, Pisani L, et al. Structures of human monoamine oxidase B complexes with selective noncovalent inhibitors: safinamide and coumarin analogs. J Med Chem 2007 Nov 15; 50(23): 5848–52PubMedCrossRef
15.
go back to reference Marzo A, Dal BL, Monti NC, et al. Pharmacokinetics and pharmacodynamics of safinamide, a neuroprotectant with antiparkinsonian and anticonvulsant activity. Pharmacol Res 2004 Jul; 50(1): 77–85PubMedCrossRef Marzo A, Dal BL, Monti NC, et al. Pharmacokinetics and pharmacodynamics of safinamide, a neuroprotectant with antiparkinsonian and anticonvulsant activity. Pharmacol Res 2004 Jul; 50(1): 77–85PubMedCrossRef
16.
go back to reference Caccia C, Salvati P, Rossetti S, et al. Safinamide: modulation of dopaminergic and glutamatergic systems. Move Disord 2008; 23(1): S22–3 Caccia C, Salvati P, Rossetti S, et al. Safinamide: modulation of dopaminergic and glutamatergic systems. Move Disord 2008; 23(1): S22–3
17.
go back to reference Ives NJ, Stowe RL, Marro J, et al. Monoamine oxidase type B inhibitors in early Parkinson’s disease: meta-analysis of 17 randomised trials involving 3525 patients. BMJ 2004 Sep 11; 329(7466): 593PubMedCrossRef Ives NJ, Stowe RL, Marro J, et al. Monoamine oxidase type B inhibitors in early Parkinson’s disease: meta-analysis of 17 randomised trials involving 3525 patients. BMJ 2004 Sep 11; 329(7466): 593PubMedCrossRef
18.
go back to reference The Parkinson Study Group. A controlled trial of rasagiline in early Parkinson disease: the TEMPO Study. Arch Neurol 2002 Dec; 59(12): 1937–43CrossRef The Parkinson Study Group. A controlled trial of rasagiline in early Parkinson disease: the TEMPO Study. Arch Neurol 2002 Dec; 59(12): 1937–43CrossRef
19.
go back to reference The Parkinson Study Group. A controlled, randomized, delayed-start study of rasagiline in early Parkinson disease. Arch Neurol 2004 Apr; 61(4): 561–6CrossRef The Parkinson Study Group. A controlled, randomized, delayed-start study of rasagiline in early Parkinson disease. Arch Neurol 2004 Apr; 61(4): 561–6CrossRef
20.
go back to reference Hauser RA, Lew MF, Hurtig HI, et al. Long-term outcome of early versus delayed rasagiline treatment in early Parkinson’s disease. Mov Disord 2009 Mar 15; 24(4): 564–73PubMedCrossRef Hauser RA, Lew MF, Hurtig HI, et al. Long-term outcome of early versus delayed rasagiline treatment in early Parkinson’s disease. Mov Disord 2009 Mar 15; 24(4): 564–73PubMedCrossRef
21.
go back to reference Olanow CW, Rascol O, Hauser R, et al. A double-blind, delayed-start trial of rasagiline in Parkinson’s disease. N Engl J Med 2009 Sep 24; 361(13): 1268–78PubMedCrossRef Olanow CW, Rascol O, Hauser R, et al. A double-blind, delayed-start trial of rasagiline in Parkinson’s disease. N Engl J Med 2009 Sep 24; 361(13): 1268–78PubMedCrossRef
22.
go back to reference The 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 Feb; 62(2): 241–8CrossRef The 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 Feb; 62(2): 241–8CrossRef
23.
go back to reference Rascol O, Brooks DJ, Melamed E, et al. 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 Mar 12; 365(9463): 947–54PubMedCrossRef Rascol O, Brooks DJ, Melamed E, et al. 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 Mar 12; 365(9463): 947–54PubMedCrossRef
24.
go back to reference Stocchi F, Arnold G, Onofrj M, et al. Improvement of motor function in early Parkinson disease by safinamide. Neurology 2004 Aug 24; 63(4): 746–8PubMedCrossRef Stocchi F, Arnold G, Onofrj M, et al. Improvement of motor function in early Parkinson disease by safinamide. Neurology 2004 Aug 24; 63(4): 746–8PubMedCrossRef
25.
go back to reference Stocchi F, Vacca L, Grassini P, et al. Symptom relief in Parkinson disease by safinamide: biochemical and clinical evidence of efficacy beyond MAO-B inhibition. Neurology 2006 Oct 10; 67(7 Suppl. 2): S24–9PubMedCrossRef Stocchi F, Vacca L, Grassini P, et al. Symptom relief in Parkinson disease by safinamide: biochemical and clinical evidence of efficacy beyond MAO-B inhibition. Neurology 2006 Oct 10; 67(7 Suppl. 2): S24–9PubMedCrossRef
26.
go back to reference Sharma T, Stocchi F, Schapira AH, et al. Satinamide treatment improves cognition in Parkinson’s disease [abstract]. Move Disord 2007 Sep; 22(12): 29 Sharma T, Stocchi F, Schapira AH, et al. Satinamide treatment improves cognition in Parkinson’s disease [abstract]. Move Disord 2007 Sep; 22(12): 29
28.
go back to reference EMD Serono. MOTION, Safinamide in Early IPD, as Addon to Dopamine Agonist [ClinicalTrials.gov identifier NCT00605683]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2010 Sep 16] EMD Serono. MOTION, Safinamide in Early IPD, as Addon to Dopamine Agonist [ClinicalTrials.gov identifier NCT00605683]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://​www.​clinicaltrials.​gov [Accessed 2010 Sep 16]
29.
go back to reference EMD Serono. Safinamide in Idiopathic Parkinson’s Disease (IPD) With Motor Fluctuations, as add-on to Levodopa (SETTLE) [ClinicalTrials.govidentifierNCT00627640]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2010 Sep 16] EMD Serono. Safinamide in Idiopathic Parkinson’s Disease (IPD) With Motor Fluctuations, as add-on to Levodopa (SETTLE) [ClinicalTrials.govidentifierNCT00627640]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://​www.​clinicaltrials.​gov [Accessed 2010 Sep 16]
30.
go back to reference Heikkila RE, Manzino L, Cabbat FS, et al. Protection against the dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine by monoamine oxidase inhibitors. Nature 1984 Oct 4; 311(5985): 467–9PubMedCrossRef Heikkila RE, Manzino L, Cabbat FS, et al. Protection against the dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine by monoamine oxidase inhibitors. Nature 1984 Oct 4; 311(5985): 467–9PubMedCrossRef
31.
go back to reference Schapira AH, Cooper JM, Dexter D, et al. Mitochondrial complex I deficiency in Parkinson’s disease [letter]. Lancet 1989 Jun 3; 1(8649): 1269PubMedCrossRef Schapira AH, Cooper JM, Dexter D, et al. Mitochondrial complex I deficiency in Parkinson’s disease [letter]. Lancet 1989 Jun 3; 1(8649): 1269PubMedCrossRef
32.
go back to reference Schapira AH, Cooper JM, Dexter D, et al. Mitochondrial complex I deficiency in Parkinson’s disease. J Neurochem 1990 Mar; 54(3): 823–7PubMedCrossRef Schapira AH, Cooper JM, Dexter D, et al. Mitochondrial complex I deficiency in Parkinson’s disease. J Neurochem 1990 Mar; 54(3): 823–7PubMedCrossRef
33.
go back to reference Owen AD, Schapira AH, Jenner P, et al. Oxidative stress and Parkinson’s disease. Ann N Y Acad Sci 1996 Jun 15; 786: 217–23PubMedCrossRef Owen AD, Schapira AH, Jenner P, et al. Oxidative stress and Parkinson’s disease. Ann N Y Acad Sci 1996 Jun 15; 786: 217–23PubMedCrossRef
34.
go back to reference Schapira AH. Oxidative stress in Parkinson’s disease. Neuropathol Appl Neurobiol 1995 Feb; 21(1): 3–9PubMedCrossRef Schapira AH. Oxidative stress in Parkinson’s disease. Neuropathol Appl Neurobiol 1995 Feb; 21(1): 3–9PubMedCrossRef
35.
go back to reference Morgan-Hughes JA, Sweeney MG, Cooper JM, et al. Mitochondrial DNA (mtDNA) diseases: correlation of genotype to phenotype. Biochim Biophys Acta 1995 May 24; 1271(1): 135–40PubMedCrossRef Morgan-Hughes JA, Sweeney MG, Cooper JM, et al. Mitochondrial DNA (mtDNA) diseases: correlation of genotype to phenotype. Biochim Biophys Acta 1995 May 24; 1271(1): 135–40PubMedCrossRef
36.
go back to reference Schapira AH, Cooper JM, Morgan-Hughes JA, et al. Molecular basis of mitochondrial myopathies: polypeptide analysis in complex-I deficiency. Lancet 1988 Mar 5; 1(8584): 500–3PubMedCrossRef Schapira AH, Cooper JM, Morgan-Hughes JA, et al. Molecular basis of mitochondrial myopathies: polypeptide analysis in complex-I deficiency. Lancet 1988 Mar 5; 1(8584): 500–3PubMedCrossRef
37.
go back to reference Tatton WG, Greenwood CE. Rescue of dying neurons: a new action for deprenyl in MPTP parkinsonism. J Neurosci Res 1991 Dec; 30(4): 666–72PubMedCrossRef Tatton WG, Greenwood CE. Rescue of dying neurons: a new action for deprenyl in MPTP parkinsonism. J Neurosci Res 1991 Dec; 30(4): 666–72PubMedCrossRef
38.
go back to reference Matsubara K, Senda T, Uezono T, et al. L-deprenyl prevents the cell hypoxia induced by dopaminergic neurotoxins, MPP(+) and beta-carbolinium: a microdialysis study in rats. Neurosci Lett 2001 Apr 20; 302(2–3): 65–8PubMedCrossRef Matsubara K, Senda T, Uezono T, et al. L-deprenyl prevents the cell hypoxia induced by dopaminergic neurotoxins, MPP(+) and beta-carbolinium: a microdialysis study in rats. Neurosci Lett 2001 Apr 20; 302(2–3): 65–8PubMedCrossRef
39.
go back to reference Kupsch A, Sautter J, Gotz ME, et al. 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): 985–1009PubMedCrossRef Kupsch A, Sautter J, Gotz ME, et al. 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): 985–1009PubMedCrossRef
40.
go back to reference Gerlach M, Foley P, Riederer P. The relevance of preclinical studies for the treatment of Parkinson’s disease. J Neurol 2003 Feb; 250 Suppl. 1:I31–4PubMedCrossRef Gerlach M, Foley P, Riederer P. The relevance of preclinical studies for the treatment of Parkinson’s disease. J Neurol 2003 Feb; 250 Suppl. 1:I31–4PubMedCrossRef
41.
go back to reference Koutsilieri E, O’Callaghan JF, Chen TS, et al. Selegiline enhances survival and neurite outgrowth of MPP(+)-treated dopaminergic neurons. Eur J Pharmacol 1994 Nov 15; 269(3): R3–4PubMedCrossRef Koutsilieri E, O’Callaghan JF, Chen TS, et al. Selegiline enhances survival and neurite outgrowth of MPP(+)-treated dopaminergic neurons. Eur J Pharmacol 1994 Nov 15; 269(3): R3–4PubMedCrossRef
42.
go back to reference Koutsilieri E, Chen TS, Rausch WD, et al. Selegiline is neuroprotective in primary brain cultures treated with 1-methyl-4-phenylpyridinium. Eur J Pharmacol 1996 Jun 13; 306(1–3): 181–6PubMedCrossRef Koutsilieri E, Chen TS, Rausch WD, et al. Selegiline is neuroprotective in primary brain cultures treated with 1-methyl-4-phenylpyridinium. Eur J Pharmacol 1996 Jun 13; 306(1–3): 181–6PubMedCrossRef
43.
go back to reference Mytilineou C, Radcliffe P, Leonardi EK, et al. L-deprenyl protects mesencephalic dopamine neurons from glutamate receptor-mediated toxicity in vitro. J Neurochem 1997 Jan; 68(1): 33–9PubMedCrossRef Mytilineou C, Radcliffe P, Leonardi EK, et al. L-deprenyl protects mesencephalic dopamine neurons from glutamate receptor-mediated toxicity in vitro. J Neurochem 1997 Jan; 68(1): 33–9PubMedCrossRef
44.
go back to reference Maruyama W, Naoi M. Neuroprotection by (−)-deprenyl and related compounds. Mech Ageing Dev 1999 Nov; 111(2–3): 189–200PubMedCrossRef Maruyama W, Naoi M. Neuroprotection by (−)-deprenyl and related compounds. Mech Ageing Dev 1999 Nov; 111(2–3): 189–200PubMedCrossRef
45.
go back to reference Maruyama W, Nitta A, Shamoto-Nagai M, et al. N-propargyl-1 (R)-aminoindan, rasagiline, increases glial cell line-derived neurotrophic factor (GDNF) in neuroblastoma SH-SY5Y cells through activation of NF-kappaB transcription factor. Neurochem Int 2004 May; 44(6): 393–400PubMedCrossRef Maruyama W, Nitta A, Shamoto-Nagai M, et al. N-propargyl-1 (R)-aminoindan, rasagiline, increases glial cell line-derived neurotrophic factor (GDNF) in neuroblastoma SH-SY5Y cells through activation of NF-kappaB transcription factor. Neurochem Int 2004 May; 44(6): 393–400PubMedCrossRef
46.
go back to reference Youdim MB, Weinstock M. Molecular basis of neuroprotective activities of rasagiline and the anti-Alzheimer drug TV3326 [(N-propargyl-(3R)aminoindan-5-YL)-ethyl methyl carbamate]. Cell Mol Neurobiol 2001 Dec; 21(6): 555–73PubMedCrossRef Youdim MB, Weinstock M. Molecular basis of neuroprotective activities of rasagiline and the anti-Alzheimer drug TV3326 [(N-propargyl-(3R)aminoindan-5-YL)-ethyl methyl carbamate]. Cell Mol Neurobiol 2001 Dec; 21(6): 555–73PubMedCrossRef
47.
go back to reference Youdim MB, Wadia A, Tatton W, et al. The anti-Parkinson drug rasagiline and its cholinesterase inhibitor derivatives exert neuroprotection unrelated to MAO inhibition in cell culture and in vivo. Ann N Y Acad Sci 2001 Jun; 939: 450–8PubMedCrossRef Youdim MB, Wadia A, Tatton W, et al. The anti-Parkinson drug rasagiline and its cholinesterase inhibitor derivatives exert neuroprotection unrelated to MAO inhibition in cell culture and in vivo. Ann N Y Acad Sci 2001 Jun; 939: 450–8PubMedCrossRef
48.
go back to reference Maruyama W, Weinstock M, Youdim MB, et al. Antiapoptotic action of anti-Alzheimer drug, TV3326 [(N-propargyl)-(3R)-aminoindan-5-yl]-ethyl methyl carbamate, a novel cholinesterase-monoamine oxidase inhibitor. Neurosci Lett 2003 May 8; 341(3): 233–6PubMedCrossRef Maruyama W, Weinstock M, Youdim MB, et al. Antiapoptotic action of anti-Alzheimer drug, TV3326 [(N-propargyl)-(3R)-aminoindan-5-yl]-ethyl methyl carbamate, a novel cholinesterase-monoamine oxidase inhibitor. Neurosci Lett 2003 May 8; 341(3): 233–6PubMedCrossRef
49.
go back to reference Bonneh-Barkay D, Ziv N, Finberg JP. Characterization of the neuroprotective activity of rasagiline in cerebellar granule cells. Neuropharmacology 2005 Mar; 48(3): 406–16PubMedCrossRef Bonneh-Barkay D, Ziv N, Finberg JP. Characterization of the neuroprotective activity of rasagiline in cerebellar granule cells. Neuropharmacology 2005 Mar; 48(3): 406–16PubMedCrossRef
50.
go back to reference Finberg JP, Takeshima T, Johnston JM, et al. Increased survival of dopaminergic neurons by rasagiline, a monoamine oxidase B inhibitor. Neuroreport 1998 Mar 9; 9(4): 703–7PubMedCrossRef Finberg JP, Takeshima T, Johnston JM, et al. Increased survival of dopaminergic neurons by rasagiline, a monoamine oxidase B inhibitor. Neuroreport 1998 Mar 9; 9(4): 703–7PubMedCrossRef
51.
go back to reference Sabi Sagi Y, Mandel S, Amit T, et al. Activation of tyrosine kinase receptor signaling pathway by rasagiline facilitates neurorescue and restoration of nigrostriatal dopamine neurons in post-MPTP-induced parkinsonism. Neurobiol Dis 2007 Jan; 25(1): 35–44CrossRef Sabi Sagi Y, Mandel S, Amit T, et al. Activation of tyrosine kinase receptor signaling pathway by rasagiline facilitates neurorescue and restoration of nigrostriatal dopamine neurons in post-MPTP-induced parkinsonism. Neurobiol Dis 2007 Jan; 25(1): 35–44CrossRef
52.
go back to reference Zhu W, Xie W, Pan T, et al. Comparison of neuroprotective and neurorestorative capabilities of rasagiline and selegiline against lactacystin-induced nigrostriatal dopaminergic degeneration. J Neurochem 2008 Jun; 105(5): 1970–8PubMedCrossRef Zhu W, Xie W, Pan T, et al. Comparison of neuroprotective and neurorestorative capabilities of rasagiline and selegiline against lactacystin-induced nigrostriatal dopaminergic degeneration. J Neurochem 2008 Jun; 105(5): 1970–8PubMedCrossRef
53.
go back to reference Chau KY, Cooper JM, Schapira AH. Rasagiline protects against alpha-synuclein induced sensitivity to oxidative stress in dopaminergic cells. Neurochem Int 2010 Nov; 57(5): 525–9PubMedCrossRef Chau KY, Cooper JM, Schapira AH. Rasagiline protects against alpha-synuclein induced sensitivity to oxidative stress in dopaminergic cells. Neurochem Int 2010 Nov; 57(5): 525–9PubMedCrossRef
54.
go back to reference Youdim MB, Bar AO, Yogev-Falach M, et al. Rasagiline: neurodegeneration, neuroprotection, and mitochondrial permeability transition. J Neurosci Res 2005 Jan 1; 79(1–2): 172–9PubMedCrossRef Youdim MB, Bar AO, Yogev-Falach M, et al. Rasagiline: neurodegeneration, neuroprotection, and mitochondrial permeability transition. J Neurosci Res 2005 Jan 1; 79(1–2): 172–9PubMedCrossRef
55.
go back to reference Seaton TA, Cooper JM, Schapira AH. Cyclosporin inhibition of apoptosis induced by mitochondrial complex I toxins. Brain Res 1998 Oct 26; 809(1): 12–7PubMedCrossRef Seaton TA, Cooper JM, Schapira AH. Cyclosporin inhibition of apoptosis induced by mitochondrial complex I toxins. Brain Res 1998 Oct 26; 809(1): 12–7PubMedCrossRef
56.
go back to reference Weinreb O, Bar-Am O, Amit T, et al. Neuroprotection via pro-survival protein kinase C isoforms associated with Bcl-2 family members. FASEB J 2004 Sep; 18(12): 1471–3PubMed Weinreb O, Bar-Am O, Amit T, et al. Neuroprotection via pro-survival protein kinase C isoforms associated with Bcl-2 family members. FASEB J 2004 Sep; 18(12): 1471–3PubMed
57.
go back to reference Maruyama W, Akao Y, Youdim MB, et al. Transfection-enforced Bcl-2 overexpression and an anti-Parkinson drug, rasagiline, prevent nuclear accumulation of glyceraldehyde3-phosphate dehydrogenase induced by an endogenous dopaminergic neurotoxin, N-methyl(R)salsolinol. J Neurochem 2001 Aug; 78(4): 727–35PubMedCrossRef Maruyama W, Akao Y, Youdim MB, et al. Transfection-enforced Bcl-2 overexpression and an anti-Parkinson drug, rasagiline, prevent nuclear accumulation of glyceraldehyde3-phosphate dehydrogenase induced by an endogenous dopaminergic neurotoxin, N-methyl(R)salsolinol. J Neurochem 2001 Aug; 78(4): 727–35PubMedCrossRef
58.
go back to reference Blandini F, Armentero MT, Fancellu R, et al. Neuroprotective effect of rasagiline in a rodent model of Parkinson’s disease. Exp Neurol 2004 Jun; 187(2): 455–9PubMedCrossRef Blandini F, Armentero MT, Fancellu R, et al. Neuroprotective effect of rasagiline in a rodent model of Parkinson’s disease. Exp Neurol 2004 Jun; 187(2): 455–9PubMedCrossRef
59.
go back to reference Weinreb O, Bar-Am O, Prosolovich K, et al. Does 1-(R)-aminoindan possess neuroprotective properties against experimental Parkinson’s disease? Antioxid Redox Signal 2011 Mar 1; 14(5): 767–75PubMedCrossRef Weinreb O, Bar-Am O, Prosolovich K, et al. Does 1-(R)-aminoindan possess neuroprotective properties against experimental Parkinson’s disease? Antioxid Redox Signal 2011 Mar 1; 14(5): 767–75PubMedCrossRef
60.
go back to reference Bar-Am O, Weinreb O, Amit T, et al. The neuroprotective mechanism of 1-(R)-aminoindan, the major metabolite of the anti-parkinsonian drug rasagiline. J Neurochem 2010 Mar; 112(5): 1131–7PubMedCrossRef Bar-Am O, Weinreb O, Amit T, et al. The neuroprotective mechanism of 1-(R)-aminoindan, the major metabolite of the anti-parkinsonian drug rasagiline. J Neurochem 2010 Mar; 112(5): 1131–7PubMedCrossRef
61.
go back to reference Schapira AH. Challenges to the development of disease-modifying therapies in Parkinson’s disease. Eur J Neurol 2011 Mar; 18 Suppl. 1: 16–21CrossRef Schapira AH. Challenges to the development of disease-modifying therapies in Parkinson’s disease. Eur J Neurol 2011 Mar; 18 Suppl. 1: 16–21CrossRef
62.
go back to reference Schapira AH, Tolosa E. Molecular and clinical prodrome of Parkinson disease: implications for treatment. Nat Rev Neurol 2010 Jun; 6(6): 309–17PubMedCrossRef Schapira AH, Tolosa E. Molecular and clinical prodrome of Parkinson disease: implications for treatment. Nat Rev Neurol 2010 Jun; 6(6): 309–17PubMedCrossRef
63.
go back to reference Olanow CW, Kieburtz K, Schapira AH. Why have we failed to achieve neuroprotection in Parkinson’s disease? Ann Neurol 2008 Dec; 64 Suppl. 2: S101–10PubMedCrossRef Olanow CW, Kieburtz K, Schapira AH. Why have we failed to achieve neuroprotection in Parkinson’s disease? Ann Neurol 2008 Dec; 64 Suppl. 2: S101–10PubMedCrossRef
64.
go back to reference Olanow CW, Schapira AH, LeWitt PA, et al. TCH346 as a neuroprotective drug in Parkinson’s disease: a double-blind, randomised, controlled trial. Lancet Neurol 2006 Dec; 5(12): 1013–20PubMedCrossRef Olanow CW, Schapira AH, LeWitt PA, et al. TCH346 as a neuroprotective drug in Parkinson’s disease: a double-blind, randomised, controlled trial. Lancet Neurol 2006 Dec; 5(12): 1013–20PubMedCrossRef
65.
go back to reference Parkinson Study Group. Effect of deprenyl on the progression of disability in early Parkinson’s disease. N Engl J Med 1989 Nov 16; 321(20): 1364–71CrossRef Parkinson Study Group. Effect of deprenyl on the progression of disability in early Parkinson’s disease. N Engl J Med 1989 Nov 16; 321(20): 1364–71CrossRef
66.
go back to reference LeWitt PA. Clinical trials of neuroprotection for Parkinson’s disease. Neurology 2004 Oct 12; 63(7 Suppl. 2): S23–31PubMedCrossRef LeWitt PA. Clinical trials of neuroprotection for Parkinson’s disease. Neurology 2004 Oct 12; 63(7 Suppl. 2): S23–31PubMedCrossRef
67.
go back to reference Shoulson I, Oakes D, Fahn S, et al. Impact of sustained deprenyl (selegiline) in levodopa-treated Parkinson’s disease: a randomized placebo-controlled extension of the deprenyl and tocopherol antioxidative therapy of parkinsonism trial. Ann Neurol 2002 May; 51(5): 604–12PubMedCrossRef Shoulson I, Oakes D, Fahn S, et al. Impact of sustained deprenyl (selegiline) in levodopa-treated Parkinson’s disease: a randomized placebo-controlled extension of the deprenyl and tocopherol antioxidative therapy of parkinsonism trial. Ann Neurol 2002 May; 51(5): 604–12PubMedCrossRef
68.
go back to reference Jenner P. Preclinical evidence for neuroprotection with monoamine oxidase-B inhibitors in Parkinson’s disease. Neurology 2004 Oct 12; 63(7 Suppl. 2): S13–22PubMedCrossRef Jenner P. Preclinical evidence for neuroprotection with monoamine oxidase-B inhibitors in Parkinson’s disease. Neurology 2004 Oct 12; 63(7 Suppl. 2): S13–22PubMedCrossRef
69.
go back to reference Palhagen S, Heinonen E, Hagglund J, et al. Selegiline slows the progression of the symptoms of Parkinson disease. Neurology 2006 Apr 25; 66(8): 1200–6PubMedCrossRef Palhagen S, Heinonen E, Hagglund J, et al. Selegiline slows the progression of the symptoms of Parkinson disease. Neurology 2006 Apr 25; 66(8): 1200–6PubMedCrossRef
70.
go back to reference Parkinson Study Group. Effects of tocopherol and deprenyl on the progression of disability in early Parkinson’s disease: the Parkinson Study Group. N Engl J Med 1993 Jan 21; 328(3): 176–83CrossRef Parkinson Study Group. Effects of tocopherol and deprenyl on the progression of disability in early Parkinson’s disease: the Parkinson Study Group. N Engl J Med 1993 Jan 21; 328(3): 176–83CrossRef
71.
go back to reference Mally J, Kovacs AB, Stone TW. Delayed development of symptomatic improvement by (−)-deprenyl in Parkinson’s disease. J Neurol Sci 1995 Dec; 134(1–2): 143–5PubMedCrossRef Mally J, Kovacs AB, Stone TW. Delayed development of symptomatic improvement by (−)-deprenyl in Parkinson’s disease. J Neurol Sci 1995 Dec; 134(1–2): 143–5PubMedCrossRef
72.
go back to reference 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 Dec 16; 311(7020): 1602–7PubMedCrossRef 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 Dec 16; 311(7020): 1602–7PubMedCrossRef
73.
go back to reference Schapira AH. Molecular and clinical pathways to neuroprotection of dopaminergic drugs in Parkinson disease. Neurology 2009 Feb 17; 72(7 Suppl. ): S44–50PubMedCrossRef Schapira AH. Molecular and clinical pathways to neuroprotection of dopaminergic drugs in Parkinson disease. Neurology 2009 Feb 17; 72(7 Suppl. ): S44–50PubMedCrossRef
74.
go back to reference Schapira AH. Science, medicine, and the future: Parkinson’s disease. BMJ 1999 Jan 30; 318(7179): 311–4PubMedCrossRef Schapira AH. Science, medicine, and the future: Parkinson’s disease. BMJ 1999 Jan 30; 318(7179): 311–4PubMedCrossRef
75.
go back to reference Fahn S, Oakes D, Shoulson I, et al. Levodopa and the progression of Parkinson’s disease. N Engl J Med 2004 Dec 9; 351(24): 2498–508PubMedCrossRef Fahn S, Oakes D, Shoulson I, et al. Levodopa and the progression of Parkinson’s disease. N Engl J Med 2004 Dec 9; 351(24): 2498–508PubMedCrossRef
76.
go back to reference Nissinen H, Kuoppamaki M, Leinonen M, et al. Early versus delayed initiation of entacapone in levodopa-treated patients with Parkinson’s disease: a long-term, retrospective analysis. Eur J Neurol 2009 Dec; 16(12): 1305–11PubMedCrossRef Nissinen H, Kuoppamaki M, Leinonen M, et al. Early versus delayed initiation of entacapone in levodopa-treated patients with Parkinson’s disease: a long-term, retrospective analysis. Eur J Neurol 2009 Dec; 16(12): 1305–11PubMedCrossRef
77.
go back to reference Schapira AH, Bezard E, Brotchie J, et al. Novel pharmacological targets for the treatment of Parkinson’s disease. Nat Rev Drug Discov 2006 Oct; 5(10): 845–54PubMedCrossRef Schapira AH, Bezard E, Brotchie J, et al. Novel pharmacological targets for the treatment of Parkinson’s disease. Nat Rev Drug Discov 2006 Oct; 5(10): 845–54PubMedCrossRef
78.
go back to reference Schapira AH, Emre M, Jenner P, et al. Levodopa in the treatment of Parkinson’s disease. Eur J Neurol 2009 Sep; 16(9): 982–9PubMedCrossRef Schapira AH, Emre M, Jenner P, et al. Levodopa in the treatment of Parkinson’s disease. Eur J Neurol 2009 Sep; 16(9): 982–9PubMedCrossRef
79.
go back to reference Schapira AH. Neurobiology and treatment of Parkinson’s disease. Trends Pharmacol Sci 2009 Jan; 30(1): 41–7PubMedCrossRef Schapira AH. Neurobiology and treatment of Parkinson’s disease. Trends Pharmacol Sci 2009 Jan; 30(1): 41–7PubMedCrossRef
80.
go back to reference Schapira AH, Obeso J. Timing of treatment initiation in Parkinson’s disease: a need for reappraisal? Ann Neurol 2006 Mar; 59(3): 559–62PubMedCrossRef Schapira AH, Obeso J. Timing of treatment initiation in Parkinson’s disease: a need for reappraisal? Ann Neurol 2006 Mar; 59(3): 559–62PubMedCrossRef
81.
go back to reference Schapira AH. Movement disorders: advances in cause and treatment. Lancet Neurol 2010 Jan; 9(1): 6–7PubMedCrossRef Schapira AH. Movement disorders: advances in cause and treatment. Lancet Neurol 2010 Jan; 9(1): 6–7PubMedCrossRef
82.
go back to reference Rascol O, Fitzer-Attas CJ, Hauser R, et al. A double-blind, delayed-start trial of rasagiline in Parkinson’s disease (the ADAGIO study): prespecified and post-hoc analyses of the need for additional therapies, changes in UPDRS scores, and non-motor outcomes. Lancet Neurol 2011 May; 10(5): 415–23PubMedCrossRef Rascol O, Fitzer-Attas CJ, Hauser R, et al. A double-blind, delayed-start trial of rasagiline in Parkinson’s disease (the ADAGIO study): prespecified and post-hoc analyses of the need for additional therapies, changes in UPDRS scores, and non-motor outcomes. Lancet Neurol 2011 May; 10(5): 415–23PubMedCrossRef
83.
go back to reference Schapira AH, Schrag A. Parkinson disease: Parkinson disease clinical subtypes and their implications. Nat Rev Neurol 2011 May; 7(5): 247–8PubMedCrossRef Schapira AH, Schrag A. Parkinson disease: Parkinson disease clinical subtypes and their implications. Nat Rev Neurol 2011 May; 7(5): 247–8PubMedCrossRef
84.
go back to reference Schapira AH. Treatment options in the modern management of Parkinson disease. Arch Neurol 2007 Aug; 64(8): 1083–8PubMedCrossRef Schapira AH. Treatment options in the modern management of Parkinson disease. Arch Neurol 2007 Aug; 64(8): 1083–8PubMedCrossRef
85.
go back to reference Schapira AH, Agid Y, Barone P, et al. Perspectives on recent advances in the understanding and treatment of Parkinson’s disease. Eur J Neurol 2009 Oct; 16(10): 1090–9PubMedCrossRef Schapira AH, Agid Y, Barone P, et al. Perspectives on recent advances in the understanding and treatment of Parkinson’s disease. Eur J Neurol 2009 Oct; 16(10): 1090–9PubMedCrossRef
Metadata
Title
Monoamine Oxidase B Inhibitors for the Treatment of Parkinson’s Disease
A Review of Symptomatic and Potential Disease-Modifying Effects
Author
Prof. Anthony H. V. Schapira
Publication date
01-12-2011
Publisher
Springer International Publishing
Published in
CNS Drugs / Issue 12/2011
Print ISSN: 1172-7047
Electronic ISSN: 1179-1934
DOI
https://doi.org/10.2165/11596310-000000000-00000

Other articles of this Issue 12/2011

CNS Drugs 12/2011 Go to the issue

Acknowledgments

Acknowledgement

Adis Drug Profile

Tetrabenazine