Abstract
Biogenic amine turnover employs the enzymes catechol-O-methyltransferase and monoamine oxidase in neuronal and glial cells. Inhibition of these enzymes elevates biogenic amine levels in the synaptic cleft. Selegiline is a selective, irreversible monoamine oxidase-B inhibitor. Its gastrointestinal absorption is fast, the maximum concentration is reached within 1 h. Main metabolites of selegiline are desmethylselegiline, methamphetamine and L-amphetamine. Symptomatic benefits of selegiline on motor symptoms in patients with Parkinson’s disease are weak. Intervals and severity of off-periods reduce after addition of selegiline, in particular during chronic levodopa intake. Selegiline increases life expectancy in levodopa-treated patients. Selegiline is administered once or twice daily, in 5 mg tablets up to 10 mg, mostly 7.5 mg. Selegiline long-term trials demonstrate, in summary, that combination of selegiline and levodopa may provide a greater clinical benefit and less progression than levodopa alone, even when levodopa without selegiline is taken at substantially higher doses.
References
Barrett JS, Hochadel TJ, Morales RJ, Rohatagi S, DeWitt KE, Watson SK, et al. Pharmacokinetics and safety of a selegiline transdermal system relative to single-dose oral administration in the elderly. Am J Ther. 1996;3(10):688–98.
Birkmayer W, Riederer P. Deprenyl prolongs the therapeutic efficacy of combined l-DOPA in Parkinson’s disease. Adv Neurol. 1984;40:475–81.
Birkmayer W, Knoll J, Riederer P, Youdim MB, Hars V, Marton J. Increased life expectancy resulting from addition of l-deprenyl to Madopar treatment in Parkinson’s disease: a long term study. J Neural Transm. 1985;64(2):113–27.
Fabbrini G, Abbruzzese G, Marconi S, Zappia M. Selegiline: a reappraisal of its role in Parkinson disease. Clin Neuropharmacol. 2012;35(3):134–40.
Fernandez HH, Chen JJ. Monoamine oxidase-B inhibition in the treatment of Parkinson’s disease. Pharmacotherapy. 2007;27(12 Pt 2):174S–85S.
Fox HH. The chemical approach to the control of tuberculosis. Science. 1952;116(3006):129–34.
Giladi N, McDermott MP, Fahn S, Przedborski S, Jankovic J, Stern M, et al. Freezing of gait in PD: prospective assessment in the DATATOP cohort. Neurology. 2001;56(12):1712–21.
Goetz CG, Leurgans S, Raman R. Placebo-associated improvements in motor function: comparison of subjective and objective sections of the UPDRS in early Parkinson’s disease. Mov Disord. 2002;17(2):283–8.
Hauser RA, Koller WC, Hubble JP, Malapira T, Busenbark K, Olanow CW. Time course of loss of clinical benefit following withdrawal of levodopa/carbidopa and bromocriptine in early Parkinson’s disease. Mov Disord. 2000;15(3):485–9.
Jankovic J, McDermott M, Carter J, Gauthier S, Goetz C, Golbe L, et al. Variable expression of Parkinson’s disease: a base-line analysis of the DATATOP cohort. The Parkinson Study Group. Neurology. 1990;40(10):1529–34.
Laine K, Anttila M, Huupponen R, Maki-Ikola O, Heinonen E. Multiple-dose pharmacokinetics of selegiline and desmethylselegiline suggest saturable tissue binding. Clin Neuropharmacol. 2000;23(1):22–7.
Larsen JP, Boas J, Erdal JE. Does selegiline modify the progression of early Parkinson’s disease? Results from a five-year study. The Norwegian-Danish Study Group. Eur J Neurol. 1999;6(5):539–47.
LeWitt P, Oakes D, Cui L. The need for levodopa as an end point of Parkinson’s disease progression in a clinical trial of selegiline and alpha-tocopherol. Parkinson Study Group. Mov Disord. 1997;12(2):183–9.
Mahmood I. Clinical pharmacokinetics and pharmacodynamics of selegiline. An update. Clin Pharmacokinet. 1997;33(2):91–102.
Mahmood I, Marinac JS, Willsie S, Mason WD. Pharmacokinetics and relative bioavailability of selegiline in healthy volunteers. Biopharm Drug Dispos. 1995;16(7):535–45.
Marras C, McDermott MP, Rochon PA, Tanner CM, Naglie G, Rudolph A, et al. Survival in Parkinson disease: thirteen-year follow-up of the DATATOP cohort. Neurology. 2005;64(1):87–93.
Olanow CW, Hauser RA, Gauger L, Malapira T, Koller W, Hubble J, et al. The effect of deprenyl and levodopa on the progression of Parkinson’s disease. Ann Neurol. 1995;38(5):771–7.
Palhagen S, Heinonen EH, Hagglund J, Kaugesaar T, Kontants H, Maki-Ikola O, et al. Selegiline delays the onset of disability in de novo parkinsonian patients. Swedish Parkinson Study Group. Neurology. 1998;51(2):520–5.
Palhagen S, Heinonen E, Hagglund J, Kaugesaar T, Maki-Ikola O, Palm R. Selegiline slows the progression of the symptoms of Parkinson disease. Neurology. 2006;66(8):1200–6.
Parkinson Study Group. Impact of deprenyl and tocopherol treatment on Parkinson’s disease in DATATOP patients requiring levodopa. Ann Neurol. 1996;39(1):37–45.
Przuntek H, Conrad B, Dichgans J, Kraus PH, Krauseneck P, Pergande G, et al. SELEDO: a 5-year long-term trial on the effect of selegiline in early Parkinsonian patients treated with levodopa. Eur J Neurol. 1999;6(2):141–50.
Riederer P, Lachenmayer L, Laux G. Clinical applications of MAO-inhibitors. Curr Med Chem. 2004;11(15):2033–43.
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Riederer, P., Müller, T. (2020). Selegiline 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_237-1
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