The effect of deprenyl and levodopa on the progression of Parkinson's disease

We have performed a 14‐month, prospective, randomized, double‐blind, placebo‐controlled study to evaluate the effect of deprenyl and levodopa/carbidopa (Sinemet) on the progression of signs and symptoms in patients with mild Parkinson's disease (PD). One hundred one untreated PD patients were randomly assigned to one of the following four treatment groups: Group I, deprenyl + Sinemet; Group II, placebo‐deprenyl + Sinemet; Group III, deprenyl + bromocriptine; and Group IV, placebo‐deprenyl + bromocriptine. The final visit was performed at 14 months, i.e., 2 months after withdrawal of deprenyl or its placebo and 7 days after withdrawal of Sinemet or bromocriptine. Deterioration in Unified Parkinson's Disease Rating Score (UPDRS) between untreated baseline and final visits was used as an index of disease progression. Placebo‐treated patients deteriorated by 5.8 ± 1.4 points, while deprenyl‐treated patients deteriorated by 0.4 ± 1.3 points (p < 0.001). This effect was sufficiently powerful that a significant deprenyl effect could be detected in the subgroup of 41 patients randomized to Sinemet (p < 0.01) as well as in the 23 patients who completed a 14‐day washout of Sinemet or bromocriptine (p < 0.05). No difference in the extent of deterioration was detected in patients randomized to Sinemet versus bromocriptine. This study demonstrates that deprenyl attenuates deterioration in UPDRS score in patients with early PD. These findings are not readily explained by the drug's symptomatic effects and are consistent with the hypothesis that deprenyl has a neuroprotective effect.

[1]  D. Holland,et al.  (−)‐Deprenyl Reduces PC12 Cell Apoptosis by Inducing New Protein Synthesis , 1994, Journal of neurochemistry.

[2]  C. Olanow A radical hypothesis for neurodegeneration , 1993, Trends in Neurosciences.

[3]  D. Murphy,et al.  Apparent antioxidant effect of l-deprenyl on hydroxyl radical formation and nigral injury elicited by MPP+ in vivo. , 1993, European journal of pharmacology.

[4]  J. Haines,et al.  Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis , 1993, Nature.

[5]  M. Brin,et al.  Effects of tocopherol and deprenyl on the progression of disability in early Parkinson's disease. , 1993, The New England journal of medicine.

[6]  C. Marsden,et al.  New insights into the cause of Parkinson's disease , 1992, Neurology.

[7]  C. W. Olanow,et al.  Neuromelanin-containing neurons of the substantia nigra accumulate iron and aluminum in Parkinson's disease: a LAMMA study , 1992, Brain Research.

[8]  C. Olanow A Rationale for Dopamine Agonists as Primary Therapy for Parkinson’s Disease , 1992, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques.

[9]  W. Tatton,et al.  Rescue of dying neurons: A new action for deprenyl in MPTP parkinsonism , 1991, Journal of neuroscience research.

[10]  P Riederer,et al.  Selective Increase of Iron in Substantia Nigra Zona Compacta of Parkinsonian Brains , 1991, Journal of neurochemistry.

[11]  C. Olanow Oxidation reactions in Parkinson's disease , 1990, Neurology.

[12]  F. Hefti,et al.  Toxicity of 6‐hydroxydopamine and dopamine for dopaminergic neurons in culture , 1990, Journal of neuroscience research.

[13]  A. Grace,et al.  Compensations after lesions of central dopaminergic neurons: some clinical and basic implications , 1990, Trends in Neurosciences.

[14]  C. Marsden,et al.  Mitochondrial Complex I Deficiency in Parkinson's Disease , 1990, Lancet.

[15]  P. Riederer,et al.  Is Parkinson's disease a progressive siderosis of substantia nigra resulting in iron and melanin induced neurodegeneration? , 1989, Acta neurologica Scandinavica. Supplementum.

[16]  Y. Kagawa,et al.  Deficiencies in complex I subunits of the respiratory chain in Parkinson's disease. , 1989, Biochemical and biophysical research communications.

[17]  J. Langston,et al.  The effect of deprenyl (selegiline) on the natural history of Parkinson's disease. , 1989, Science.

[18]  C. Marsden,et al.  Increased Nigral Iron Content and Alterations in Other Metal Ions Occurring in Brain in Parkinson's Disease , 1989, Journal of neurochemistry.

[19]  Peter Riederer,et al.  Transition Metals, Ferritin, Glutathione, and Ascorbic Acid in Parkinsonian Brains , 1989, Journal of neurochemistry.

[20]  C. Marsden,et al.  Basal Lipid Peroxidation in Substantia Nigra Is Increased in Parkinson's Disease , 1989, Journal of neurochemistry.

[21]  G. Cohen,et al.  Exposure of striatal [corrected] synaptosomes to L-dopa increases levels of oxidized glutathione. , 1988, The Journal of pharmacology and experimental therapeutics.

[22]  C. D. Arnett,et al.  Turnover of Brain Monoamine Oxidase Measured In Vivo by Positron Emission Tomography Using l‐[11C]Deprenyl , 1987, Journal of neurochemistry.

[23]  B. Halliwell,et al.  Oxygen radicals and the nervous system , 1985, Trends in Neurosciences.

[24]  M. Yahr,et al.  Pargyline and deprenyl prevent the neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in monkeys. , 1984, European journal of pharmacology.

[25]  R. Clavier,et al.  Nigrostriatal Dopaminergic Neurons Remain Undamaged in Rats Given High Doses of l‐DOPA and Carbidopa Chronically , 1984, Journal of neurochemistry.

[26]  D. Godin,et al.  Parkinson's disease: A disorder due to nigral glutathione deficiency? , 1982, Neuroscience Letters.

[27]  R. Wurtman,et al.  Long‐term administration of L‐DOPA does not damage dopaminergic neurons in the mouse , 1981, Neurology.

[28]  K. Jellinger,et al.  Brain dopamine and the syndromes of Parkinson and Huntington. Clinical, morphological and neurochemical correlations. , 1973, Journal of the neurological sciences.

[29]  W. Tatton,et al.  Reduction of neuronal apoptosis by small molecules: Promise for new approaches to neurological therapy , 1996 .

[30]  C. Olanow,et al.  An introduction to the free radical hypothesis in Parkinson's disease , 1992, Annals of neurology.

[31]  J. Langston,et al.  Oxidation reactions in Parkinson's disease. Discussion , 1990 .

[32]  Anthony E. Lang,et al.  Effect of deprenyl on the progression of disability in early Parkinson's disease. , 1989, The New England journal of medicine.

[33]  N. Quinn,et al.  Preservation of the substanitia nigra and locus coeruleus in a patient receiving levodopa (2 kg) plus decarboxylase inhibitor over a four‐year period , 1986, Movement disorders : official journal of the Movement Disorder Society.

[34]  M. M. Maier Hoehn Parkinsonism treated with levodopa: progression and mortality. , 1983, Journal of neural transmission. Supplementum.