Desmethylselegiline, a metabolite of selegiline, is an irreversible inhibitor of monoamine oxidase type B in humans

Journal of Clinical Pharmacology

Volumn 37, Issue 7, 1997, Pages 602-609

  Heinonen, Esa H ^a,b   Anttila, Markku I ^a   Karnani, Hari L ^a   Nyman, Leena M ^a   Vuorinen, Jouni A ^a   Pyykkö, Kaija A ^a   Lammintausta, Risto A S ^a  

^a UNIVERSITY OF TURKU   (Finland)

^b ORION CORPORATION   (Finland)

Author keywords

[No Author keywords available]

Indexed keywords

DRUG METABOLITE; MONOAMINE OXIDASE INHIBITOR; SELEGILINE;

ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; CROSSOVER PROCEDURE; DOUBLE BLIND PROCEDURE; DRUG BIOAVAILABILITY; ENZYME INHIBITION; HUMAN; ORAL DRUG ADMINISTRATION; PARKINSON DISEASE; THROMBOCYTE ACTIVATION;

EID: 0030879007     PISSN: 00912700     EISSN: None     Source Type: Journal    
DOI: 10.1002/j.1552-4604.1997.tb04342.x     Document Type: Article

References (37)

1. Knoll J: The possible mechanisms of action of (-)deprenyl in Parkinson's disease. J. Neural Transm 1978; 43:177-198.
2. Riederer P, Youdim MBH, Rausch WD, Birkmayer W, Jellinger K, Seemann D: On the mode of action of L-Deprenyl in the human central nervous system. J. Neural Transm 1978; 43:217-226.
3. Myllylä VV, Sotaniemi KA, Vuorinen JA, Heinonen EH: Selegiline as initial treatment in de novo parkinsonian patients. Neurology 1992; 42:339-343.
4. Tetrud JW, Langston JW: The effect of deprenyl (selegiline) on the natural history of Parkinson's disease. Science 1989; 245:519-522.
5. The Parkinson Study Group: Effects of tocopherol and deprenyl on the progression of disability in early Parkinson's disease. N Engl J Med 1993; 328:176-183.
6. Allain H, Cougnard J, Neukirch H-C, the FSMT members: The French Selegiline Multicenter Trial (FSMT). Acta Neurol Scand 1991; 84 (suppl 136):73-78.
7. Chrisp P, Mammen GJ, Sorkin EM: Selegiline: a review of its pharmacology, symptomatic benefits and protective potential in Parkinson's disease. Drugs Aging 1991; 1:228-248.
8. Heinonen EH, Rinne UK: Selegiline in the treatment of Parkinson's disease. Acta Neurol Scand 1989; 80(126):103-111.
9. Finnegan KT, Skratt JJ, Irwin I, DeLanney LE, Langsten JW: Protection against DSP-4-induced neurotoxicity by deprenyl is not related to its inhibition of MAO B. Eur J Pharmacol 1990; 184:119-126.
10. Heikkila RE, Manzino L, Cabbat FS, Duvoisin RC: Protection against the dopaminergic neurotoxicitv of 1-methyl-4-phenyl-1,2,5.6-tetrahydropyridine by monoamine oxidase inhibitors. Nature 1984; 311:467-469.
11. Rinne JO, Röyttä M, Paljärvi L, Rummukainen J, Rinne UK: Selegiline (deprenyl) treatment and death of nigral neurons in Parkinson's disease. Neurology 1991; 41:859-861.
12. Salo PT, Tatton WG: Deprenyl reduces the death of motoneurons caused by axotomy. J Neurosci Res 1992; 31:394-400.
13. Tatton WG, Greenwood CE: Rescue of dying neurons: a new action for deprenyl in MPTP parkinsonism. J Neurosci Res 1991; 30:666-672.
14. Heinonen EH, Anttila M, Karnani H, Lammintausta R: Pharmacokinetics of selegiline after oral dosing. Mov Disord 1994; 9(suppl 1):P248.
15. Yoshida T, Yamada Y, Yamamoto T, Kuroiwa Y: Melabohsm of deprenyl, a selective monoamine oxidase (MAO) B inhibitor in rat: relationship of metabolism to MAO-B inhibitory potency. Xenobiotica 1986; 16:129-136.
16. Borbe HO, Niebch G, Nickel B: Kinetic evaluation of MAO-B-activity following oral administration of selegiline and desmethylselegiline in rat. J Neural Transm 1990; 32(suppl):131-137.
17. Murphy DL, Donelly CH: Monoamine oxidase in man: enzyme characteristics in human platelets, plasma and other tissues. Adv Biochem Psycopharmacol 1974; 12:71-86.
18. Elsworth JD, Glover V, Reynolds GP, Sandler M, Lees AJ, Phuapradit P, et al: Deprenyl administration in man: a selective monoamine oxidase B inhibitor without the 'cheese effect'. Psychopharmacology 1978; 57:33-38.
19. Liebowitz MR, Karoum F, Quitkin FM, Davies SO, Schwartz D, Levitt M, Linnoila M: Biochemical effects of L-deprenyl in atypical depressives. Biol Psychiatry 1985; 20:558-565.
20. Keller HH, Kettler R, Keller G, Da Prada M: Short acting novel MAO inhibitors: in vitro evidence of the reversibility of MAO inhibition by moclobemide and Ro-16-6491. Naunyn Schmiedebergs Arch Pharmacol 1987; 335:12-20.
21. Salonen JS: Determination of amine metabolites of selegiline in biological fluids by capillary gas chromatography. J Chromatogr 1990; 527:163-168.
22. Wallenstein S, Fisher AC: The analysis of the two-period repeated measurements crossover design with application to clinical trials. Biometrics 1977; 33:261-269.
23. Grieve AP: The two-period changeover design in clinical trials (letter). Biometrics 1982; 38:518.
24. Grizzle JE: The two-period changeover design and its use in clinical trials. Biometrics 1965; 21:467-480.
25. Donner A, Wells G: A comparison of confidence interval methods for the intraclass correlation coefficient. Boimetrics 1986; 42:401-412.
26. Birkmayer W, Riederer P, Ambrozi L, Youdim MBH: Implications of combined treatment with 'Madopar' and 1-deprenyl in Parkinson's disease. Lancet 1977; 1:439-443.
27. Lee DH, Mendoza M, Dvorozniak MT, Chung E, van Woert MH, Yahr MD: Platelet monoamine oxidase in Parkinson patients: effect of L-deprenyl therapy. J Neural Transm 1989; 1:189-194.
28. Stern GM, Lees AJ, Sandler M: Recent observations on the clinical pharmacology of (-)deprenyl. J Neural Transm 1978; 43:245-251.
29. Wajsbort J, Kartmazov K, Oppenheim B, Barkey R, Youdim MBH: The clinical and biochemical investigation of L-deprenyl in Parkinson's disease with special reference to the "on-off" effect. J Neural Transm 1982; 55:201-215.
30. Cesura AM, Pletscher A: The generation of monoamine oxidase inhibitors. In, Jucker E (ed.): Progress in Drug Research. Basel: Birkhäuser Verlag, 1992; 174-297.
31. Tatton W, Wadia J, Ju W, Zhang F, Holland D, Seniuk-Tatton N, Tai C: (-)-Deprenyl prevents mitochondrial depolarization and reduces programmed cell death in trophically-deprived cells. New Trends Clin Neuropharmacol 7(1):34-35.
32. Heinonen EH, Anttila MI, Lammintausta RAS: Pharmacokinetics and clinical pharmacology of selegiline. In, Szelenyi I (ed.): Inhibitors of Monoamine Oxidase B. Basel: Birkhäuser Verlag Ag, 1992; 201-213.
33. Heinonen EH, Anttila MI, Nyman LM, Pyykkö KA, Vuorinen JA, Lammintausta RAS: Inhibition of platelet monoamine oxidase type B by selegiline. J Clin Pharmacol 1997; 37:597-601.
34. Filinger EJ, Stefano FJE: Monoamine oxidase inhibition by d-amphetamine in ganglia and nerve endings. Experimentia 1982; 38:844-845.
35. Arai Y, Kim SK, Kinemuchi H, Tadano T, Satoh S-E, Satoh N, Kisara K: Inhibition of brain type A monoamine oxidase and 5-hydroxytryptamine uptake by two amphetamine metabolites, p-hydroxyamphetamine and p-hydroxynorephedrine. J Neurochem 1990; 55:403-408.
36. Mahmood I, Neau SH, Mason WD: An enzymatic assay for the MAO-B inhibitor selegiline in plasma. J Pharm Biomed Anal 1994; 12:895-899.
37. Mytilineou C, Radcliffe PM, Olanow CW: L-(-)-Desmethylselegiline, a metabolite of selegiline [L-(-)-deprenenyl], protects mesencephalic dopaminergic neurons from excitotoxicity in vitro. J Neurochem 1997; 68:434-436.