Deuterium-substituted l-DOPA displays increased behavioral potency and dopamine output in an animal model of Parkinson’s disease: comparison with the effects produced by l-DOPA and an MAO-B inhibitor

Journal of Neural Transmission

Volumn 122, Issue 2, 2015, Pages 259-272

  Malmlöf, Torun ^a   Feltmann, Kristin ^a   Konradsson Geuken, Åsa ^a   Schneider, Frank ^b   Alken, Rudolf Giesbert ^c   Svensson, Torgny H ^a   Schilström, Björn ^a  

^a KAROLINSKA INSTITUTE   (Sweden)

^b CDRD Berolina AB   (Germany)

^c BiRDS Pharma GmbH   (Germany)

Author keywords

Deuterium; Dopamine; l DOPA; Metabolism; Parkinson s disease; Selegiline

Indexed keywords

ADRENERGIC RECEPTOR STIMULATING AGENT; ANTIPARKINSON AGENT; DEUTERIUM; DOPAMINE; LEVODOPA; MONOAMINE OXIDASE INHIBITOR; OXIDOPAMINE; SELEGILINE; TYROSINE 3 MONOOXYGENASE;

ANIMAL; ANIMAL BEHAVIOR; BRAIN; DISEASE MODEL; DRUG EFFECTS; FORELIMB; MALE; METABOLISM; MICRODIALYSIS; MOTOR ACTIVITY; PARKINSON DISEASE; PATHOLOGY; PATHOPHYSIOLOGY; RAT; WISTAR RAT;

ADRENERGIC AGENTS; ANIMALS; ANTIPARKINSON AGENTS; BEHAVIOR, ANIMAL; BRAIN; DEUTERIUM; DISEASE MODELS, ANIMAL; DOPAMINE; FORELIMB; LEVODOPA; MALE; MICRODIALYSIS; MONOAMINE OXIDASE INHIBITORS; MOTOR ACTIVITY; OXIDOPAMINE; PARKINSON DISEASE; RATS; RATS, WISTAR; SELEGILINE; TYROSINE 3-MONOOXYGENASE;

EID: 84939873977     PISSN: 03009564     EISSN: 14351463     Source Type: Journal    
DOI: 10.1007/s00702-014-1247-6     Document Type: Article

References (66)

1. Arai R, Karasawa N, Geffard M, Nagatsu I (1995) l-DOPA is converted to dopamine in serotonergic fibers of the striatum of the rat: a double-labeling immunofluorescence study. Neurosci Lett 195:195–198
2. Arai R, Karasawa N, Kurokawa K, Kanai H, Horiike K, Ito A (2002) Differential subcellular location of mitochondria in rat serotonergic neurons depends on the presence and the absence of monoamine oxidase type B. Neuroscience 114:825–835
3. Azzaro AJ, Demarest KT (1982) Inhibitory effects of type A and type B monoamine oxidase inhibitors on synaptosomal accumulation of [3H]dopamine: a reflection of antidepressant potency. Biochem Pharmacol 31:2195–2197
4. Barnum CJ, Bhide N, Lindenbach D, Surrena MA, Goldenberg AA, Tignor S, Klioueva A, Walters H, Bishop C (2012) Effects of noradrenergic denervation on l-DOPA-induced dyskinesia and its treatment by alpha- and beta-adrenergic receptor antagonists in hemiparkinsonian rats. Pharmacol Biochem Behav 100:607–615
5. Bartl J, Müller T, Grünblatt E, Gerlach M, Riederer P (2014) Chronic monoamine oxidase-B inhibitor treatment blocks monoamine oxidase-A enzyme activity. J Neural Transm 121:379–383
6. Brown EE, Damsma G, Cumming P, Fibiger HC (1991) Interstitial 3-methoxytyramine reflects striatal dopamine release: an in vivo microdialysis study. J Neurochem 57:701–707
7. Butcher SP, Fairbrother IS, Kelly JS, Arbuthnott GW (1990) Effects of selective monoamine oxidase inhibitors on the in vivo release and metabolism of dopamine in the rat striatum. J Neurochem 55:981–988
8. Cenci MA, Whishaw IQ, Schallert T (2002) Animal models of neurological deficits: how relevant is the rat? Nat Rev Neurosci 3:574–579
9. Colzi A, D’Agostini F, Cesura AM, Borroni E, Da Prada M (1993) Monoamine oxidase-A inhibitors and dopamine metabolism in rat caudatus: evidence that an increased cytosolic level of dopamine displaces reversible monoamine oxidase-A inhibitors in vivo. J Pharmacol Exp Ther 265:103–111
10. Di Chiara G, Tanda G, Carboni E (1996) Estimation of in vivo neurotransmitter release by brain microdialysis: the issue of validity. Behav Pharmacol 7:640–657
11. Encarnacion EV, Hauser RA (2008) Levodopa-induced dyskinesias in Parkinson’s disease: etiology, impact on quality of life, and treatments. Eur Neurol 60:57–66
12. Fagervall I, Ross SB (1986) A and B forms of monoamine oxidase within the monoaminergic neurons of the rat brain. J Neurochem 47:569–576
13. Finberg JP, Wang J, Goldstein DS, Kopin IJ, Bankiewicz KS (1995) Influence of selective inhibition of monoamine oxidase A or B on striatal metabolism of l-DOPA in hemiparkinsonian rats. J Neurochem 65:1213–1220
14. Fulceri F, Biagioni F, Ferrucci M, Lazzeri G, Bartalucci A, Galli V, Ruggieri S, Paparelli A, Fornai F (2007) Abnormal involuntary movements (AIMs) following pulsatile dopaminergic stimulation: severe deterioration and morphological correlates following the loss of locus coeruleus neurons. Brain Res 1135:219–229
15. Hefti F, Melamed E, Wurtman RJ (1981) The site of dopamine formation in rat striatum after l-dopa administration. J Pharmacol Exp Ther 217:189–197
16. Heinonen EH, Rinne UK (1989) Selegiline in the treatment of Parkinson’s disease. Acta Neurol Scand Suppl 126:103–111
17. Ives NJ, Stowe RL, Marro J, Counsell C, Macleod A, Clarke CE, Gray R, Wheatley K (2004) Monoamine oxidase type B inhibitors in early Parkinson’s disease: meta-analysis of 17 randomised trials involving 3525 patients. BMJ 329:593
18. Jahng JW, Houpt TA, Wessel TC, Chen K, Shih JC, Joh TH (1997) Localization of monoamine oxidase A and B mRNA in the rat brain by in situ hybridization. Synapse 25:30–36
19. Kannari K, Tanaka H, Maeda T, Tomiyama M, Suda T, Matsunaga M (2000) Reserpine pretreatment prevents increases in extracellular striatal dopamine following l-DOPA administration in rats with nigrostriatal denervation. J Neurochem 74:263–269
20. Kannari K, Shen H, Arai A, Tomiyama M, Baba M (2006) Reuptake of l-DOPA-derived extracellular dopamine in the striatum with dopaminergic denervation via serotonin transporters. Neurosci Lett 402:62–65
21. Karhunen T, Tilgmann C, Ulmanen I, Panula P (1995) Catechol-O-methyltransferase (COMT) in rat brain: immunoelectron microscopic study with an antiserum against rat recombinant COMT protein. Neurosci Lett 187:57–60
22. Karoum F, Chuang LW, Eisler T, Calne DB, Liebowitz MR, Quitkin FM, Klein DF, Wyatt RJ (1982) Metabolism of (-) deprenyl to amphetamine and methamphetamine may be responsible for deprenyl’s therapeutic benefit: a biochemical assessment. Neurology 32:503–509
23. Kastner A, Anglade P, Bounaix C, Damier P, Javoy-Agid F, Bromet N, Agid Y, Hirsch EC (1994) Immunohistochemical study of catechol-O-methyltransferase in the human mesostriatal system. Neuroscience 62:449–457
24. Kato T, Dong B, Ishii K, Kinemuchi H (1986) Brain dialysis: in vivo metabolism of dopamine and serotonin by monoamine oxidase A but not B in the striatum of unrestrained rats. J Neurochem 46:1277–1282
25. Kuczenski R, Segal DS (1992) Differential effects of amphetamine and dopamine uptake blockers (cocaine, nomifensine) on caudate and accumbens dialysate dopamine and 3-methoxytyramine. J Pharmacol Exp Ther 262:1085–1094
26. Kushner DJ, Baker A, Dunstall TG (1999) Pharmacological uses and perspectives of heavy water and deuterated compounds. Can J Physiol Pharmacol 77:79–88
27. Lai JC, Leung TK, Guest JF, Lim L, Davison AN (1980) The monoamine oxidase inhibitors clorgyline and L-deprenyl also affect the uptake of dopamine, noradrenaline and serotonin by rat brain synaptosomal preparations. Biochem Pharmacol 29:2763–2767
28. Lamensdorf I, Youdim MB, Finberg JP (1996) Effect of long-term treatment with selective monoamine oxidase A and B inhibitors on dopamine release from rat striatum in vivo. J Neurochem 67:1532–1539
29. Larsen JP, Boas J, Erdal JE (1999) Does selegiline modify the progression of early Parkinson’s disease? Results from a five-year study. The Norwegian-Danish Study Group. Eur J Neurol 6:539–547
30. Levitt P, Pintar JE, Breakefield XO (1982) Immunocytochemical demonstration of monoamine oxidase B in brain astrocytes and serotonergic neurons. Proc Natl Acad Sci USA 79:6385–6389
31. Li XM, Juorio AV, Paterson IA, Walz W, Zhu MY, Boulton AA (1992) Gene expression of aromatic L-amino acid decarboxylase in cultured rat glial cells. J Neurochem 59:1172–1175
32. Lindgren HS, Andersson DR, Lagerkvist S, Nissbrandt H, Cenci MA (2010) l-DOPA-induced dopamine efflux in the striatum and the substantia nigra in a rat model of Parkinson’s disease: temporal and quantitative relationship to the expression of dyskinesia. J Neurochem 112:1465–1476
33. Lopez-Real A, Rodriguez-Pallares J, Guerra MJ, Labandeira-Garcia JL (2003) Localization and functional significance of striatal neurons immunoreactive to aromatic L-amino acid decarboxylase or tyrosine hydroxylase in rat Parkinsonian models. Brain Res 969:135–146
34. Lundblad M, Andersson M, Winkler C, Kirik D, Wierup N, Cenci MA (2002) Pharmacological validation of behavioural measures of akinesia and dyskinesia in a rat model of Parkinson’s disease. Eur J Neurosci 15:120–132
35. Malmlöf T, Svensson TH, Schilström B (2008) Altered behavioural and neurochemical profile of l-DOPA following deuterium substitutions in the molecule. Exp Neurol 212:538–542
36. Malmlöf T, Rylander D, Alken RG, Schneider F, Svensson TH, Cenci MA, Schilström B (2010) Deuterium substitutions in the l-DOPA molecule improve its anti-akinetic potency without increasing dyskinesias. Exp Neurol 225:408–415
37. Melamed E, Hefti F, Pettibone DJ, Liebman J, Wurtman RJ (1981) Aromatic L-amino acid decarboxylase in rat corpus striatum: implications for action of l-dopa in parkinsonism. Neurology 31:651–655
38. Mercuri NB, Bernardi G (2005) The ‘magic’ of l-dopa: why is it the gold standard Parkinson’s disease therapy? Trends Pharmacol Sci 26:341–344
39. Miller DW, Abercrombie ED (1999) Role of high-affinity dopamine uptake and impulse activity in the appearance of extracellular dopamine in striatum after administration of exogenous l-DOPA: studies in intact and 6-hydroxydopamine-treated rats. J Neurochem 72:1516–1522
40. Mura A, Jackson D, Manley MS, Young SJ, Groves PM (1995) Aromatic L-amino acid decarboxylase immunoreactive cells in the rat striatum: a possible site for the conversion of exogenous l-DOPA to dopamine. Brain Res 704:51–60
41. Mura A, Linder JC, Young SJ, Groves PM (2000) Striatal cells containing aromatic L-amino acid decarboxylase: an immunohistochemical comparison with other classes of striatal neurons. Neuroscience 98:501–511
42. Nakamura K, Ahmed M, Barr E, Leiden JM, Kang UJ (2000) The localization and functional contribution of striatal aromatic L-amino acid decarboxylase to l-3,4-dihydroxyphenylalanine decarboxylation in rodent parkinsonian models. Cell Transplant 9:567–576
43. Navailles S, Bioulac B, Gross C, De Deurwaerdere P (2010) Serotonergic neurons mediate ectopic release of dopamine induced by l-DOPA in a rat model of Parkinson’s disease. Neurobiol Dis 38:136–143
44. Nevalainen N, Af Bjerken S, Lundblad M, Gerhardt GA, Strömberg I (2011) Dopamine release from serotonergic nerve fibers is reduced in l-DOPA-induced dyskinesia. J Neurochem 118:12–23
45. Nirenberg MJ, Chan J, Liu Y, Edwards RH, Pickel VM (1997) Vesicular monoamine transporter-2: immunogold localization in striatal axons and terminals. Synapse 26:194–198
46. Nutt JG (2008) Pharmacokinetics and pharmacodynamics of levodopa. Mov Disord 23(Suppl 3):S580–S584
47. Pålhagen S, Heinonen E, Hägglund J, Kaugesaar T, Maki-Ikola O, Palm R (2006) Selegiline slows the progression of the symptoms of Parkinson disease. Neurology 66:1200–1206
48. Paterson IA, Juorio AV, Berry MD, Zhu MY (1991) Inhibition of monoamine oxidase-B by (-)-deprenyl potentiates neuronal responses to dopamine agonists but does not inhibit dopamine catabolism in the rat striatum. J Pharmacol Exp Ther 258:1019–1026
49. Paxinos G, Watson C (2008) The rat brain in stereotaxic coordinates, 6th edn. Academic Press, San Diego
50. Reynolds GP, Elsworth JD, Blau K, Sandler M, Lees AJ, Stern GM (1978) Deprenyl is metabolized to methamphetamine and amphetamine in man. Br J Clin Pharmacol 6:542–544
51. Riederer P, Youdim MB (1986) Monoamine oxidase activity and monoamine metabolism in brains of parkinsonian patients treated with l-deprenyl. J Neurochem 46:1359–1365
52. Sader-Mazbar O, Loboda Y, Rabey MJ, Finberg JPM (2013) Increased l-dopa-derived dopamine following selective MAO-A or -B inhibition in rat striatum depleted of dopaminergic and serotonergic innervations. Br J Pharmacol 170:999–1013
53. Schrag A, Quinn N (2000) Dyskinesias and motor fluctuations in Parkinson’s disease. A community-based study. Brain 123(Pt 11):2297–2305
54. Schwarting RK, Huston JP (1996) The unilateral 6-hydroxyopamine lesion model in behavioral brain research. Analysis of functional deficits, recovery and treatments. Prog Neurobiol 50:275–331
55. Sharma JC, Macnamara L, Hasoon M, Vassallo M, Ross I (2006) Cascade of levodopa dose and weight-related dyskinesia in Parkinson’s disease (LD-WD-PD cascade). Parkinsonism Relat Disord 12:499–505
56. Sharma JC, Ross IN, Rascol O, Brooks D (2008) Relationship between weight, levodopa and dyskinesia: the significance of levodopa dose per kilogram body weight. Eur J Neurol 15:493–496
57. Stanley N, Salem A, Irvine RJ (2007) The effects of co-administration of 3,4-methylenedioxymethamphetamine (“ecstasy”) or para-methoxyamphetamine and moclobemide at elevated ambient temperatures on striatal 5-HT, body temperature and behavior in rats. Neuroscience 146:321–329
58. Tanaka H, Kannari K, Maeda T, Tomiyama M, Suda T, Matsunaga M (1999) Role of serotonergic neurons in l-DOPA-derived extracellular dopamine in the striatum of 6-OHDA-lesioned rats. Neuroreport 10:631–634
59. Tashiro Y, Kaneko T, Sugimoto T, Nagatsu I, Kikuchi H, Mizuno N (1989) Striatal neurons with aromatic L-amino acid decarboxylase-like immunoreactivity in the rat. Neurosci Lett 100:29–34
60. Ungerstedt U (1971) Postsynaptic supersensitivity after 6-hydroxy-dopamine induced degeneration of the nigro-striatal dopamine system. Acta Physiol Scand Suppl 367:69–93
61. Ungerstedt U (1976) 6-hydroxydopamine-inuced degeneration of the dopaminergic pathway: the turning syndrome. Pharmacol Ther B 2:37–40
62. Wachtel SR, Abercrombie ED (1994) L-3,4-dihydroxyphenylalanine-induced dopamine release in the striatum of intact and 6-hydroxydopamine-treated rats: differential effects of monoamine oxidase A and B inhibitors. J Neurochem 63:108–117
63. Waldmeier PC (1987) Amine oxidases and their endogenous substrates (with special reference to monoamine oxidase and the brain). J Neural Transm Suppl 23:55–72
64. Westlund KN, Denney RM, Rose RM, Abell CW (1988) Localization of distinct monoamine oxidase A and monoamine oxidase B cell populations in human brainstem. Neuroscience 25:439–456
65. Yamada H, Aimi Y, Nagatsu I, Taki K, Kud M, Arai R (2007) Immunohistochemical detection of l-DOPA-derived dopamine within serotonergic fibers in the striatum and the substantia nigra pars reticulata in Parkinsonian model rats. Neurosci Res 59:1–7
66. Yu PH, Bailey BA, Durden DA, Boulton AA (1986) Stereospecific deuterium substitution at the alpha-carbon position of dopamine and its effect on oxidative deamination catalyzed by MAO-A and MAO-B from different tissues. Biochem Pharmacol 35:1027–1036