KNS-760704 [(6R)-4,5,6,7-tetrahydro-N6-propyl-2, 6-benzothiazole-diamine dihydrochloride monohydrate] for the treatment of amyotrophic lateral sclerosis

CNS Neuroscience and Therapeutics

Volumn 14, Issue 3, 2008, Pages 215-226

  Gribkoff, Valentin K ^a   Bozik, Michael E ^a  

^a Knopp Neurosciences Inc   (United States)

Author keywords

(R) (+) pramipexole; Benzothiazole; Enantiomer; KNS 760704; Mirapex ; Mitochondria; Neuroprotection; Pramipexole; Rilutek

Indexed keywords

4,5,6,7 TETRAHYDRO N6 PROPYL 2,6 BENZOTHIAZOLEDIAMINE; BENZOTHIAZOLE DERIVATIVE; DOPAMINE RECEPTOR; KNS 760704; PRAMIPEXOLE; REACTIVE OXYGEN METABOLITE; RILUZOLE;

ABSENCE OF SIDE EFFECTS; AMYOTROPHIC LATERAL SCLEROSIS; APOPTOSIS; CAUSE OF DEATH; CELL ASSAY; CELL SURVIVAL; CLINICAL TRIAL; CONCENTRATION RESPONSE; DISEASE COURSE; DISEASE MODEL; DISORDERS OF MITOCHONDRIAL FUNCTIONS; DRUG ACTIVITY; DRUG BLOOD LEVEL; DRUG EFFICACY; DRUG MECHANISM; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SAFETY; DRUG TOLERABILITY; HUMAN; IN VITRO STUDY; IN VIVO STUDY; MITOCHONDRION; MOTONEURON; NERVE DEGENERATION; NEUROPROTECTION; NONHUMAN; PARKINSON DISEASE; RESPIRATORY FAILURE; REVIEW; SINGLE DRUG DOSE; UNSPECIFIED SIDE EFFECT;

AMYOTROPHIC LATERAL SCLEROSIS; ANIMALS; BENZOTHIAZOLES; DOPAMINE AGONISTS; HUMANS; MITOCHONDRIA; NEUROPROTECTIVE AGENTS; STEREOISOMERISM;

EID: 49849097899     PISSN: 17555930     EISSN: 17555949     Source Type: Journal    
DOI: 10.1111/j.1755-5949.2008.00048.x     Document Type: Review

References (119)

1. Boillee S, Vande VC, Cleveland DW. ALS: A disease of motor neurons and their nonneuronal neighbors. Neuron 2006 52 : 39 59.
2. Brooks BR. Natural history of ALS: Symptoms, strength, pulmonary function, and disability. Neurology 1996 47 : S71 S81.
3. Jackson CE, Bryan WW. Amyotrophic lateral sclerosis. Semin Neurol 1998 18 : 27 39.
4. Palmowski A, Jost WH, Prudlo J, Osterhage J, Kasmann B, Schimrigk K, Ruprecht KW. Eye movement in amyotrophic lateral sclerosis: A longitudinal study. Ger J Ophthalmol 1995 4 : 355 362.
5. Irwin D, Lippa CF, Swearer JM. Cognition and amyotrophic lateral sclerosis (ALS). Am J Alzheimers Dis Other Demen 2007 22 : 300 312.
6. Arai T, Hasegawa M, Akiyama H, Ikeda K, Nonaka T, Mori H, Mann O, Tsuchiya K, Yoshida M, Hashizame Y, et al. TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Biochem Biophys Res Commun 2006 351 : 602 611.
7. Dickson DW, Josephs KA, Mador-Ortiz C. TDP-43 in differential diagnosis of motor neuron disorders. Acta Neuropathol 2007 114 : 71 79.
8. Beghi E, Logroscino G, Chio A, Hardiman O, Mitchell D, Swingler R, Traynor BJ. The epidemiology of ALS and the role of population-based registries. Biochim Biophys Acta 2006 1762 : 1150 1157.
9. Brooks BR. Clinical epidemiology of amyotrophic lateral sclerosis. Neurol Clin 1996 14 : 399 420.
10. Strong M, Rosenfeld J. Amyotrophic lateral sclerosis: A review of current concepts. Amyotroph Lateral Scler Other Motor Neuron Disord 2003 4 : 136 143.
11. Brown RH, Jr. Amyotrophic lateral sclerosis. Insights from genetics Arch Neurol 1997 54 : 1246 1250.
12. Bruijn LI, Miller TM, Cleveland DW. Unraveling the mechanisms involved in motor neuron degeneration in ALS. Annu Rev Neurosci 2004 27 : 723 749.
13. Cleveland DW, Rothstein JD. From Charcot to Lou Gehrig: Deciphering selective motor neuron death in ALS. Nat Rev Neurosci 2001 2 : 806 819.
14. Majoor-Krakauer D, Willems PJ, Hofman A. Genetic epidemiology of amyotrophic lateral sclerosis. Clin Genet 2003 63 : 83 101.
15. Rosen DR, Bowling AC, Patterson D, Usdin TB, Sapp P, Mezey E, McKenna-Yasek D, O'Regan J, Rahmani Z, Ferrante RJ, et al. A frequent ala 4 to val superoxide dismutase-1 mutation is associated with a rapidly progressive familial amyotrophic lateral sclerosis. Hum Mol Genet 1994 3 : 981 987.
16. Wong PC, Pardo CA, Borchelt DR, Lee MK, Copeland NG, Jenkins NA, Sisodia SS, Cleveland DW, Price DL. An adverse property of a familial ALS-linked SOD1 mutation causes motor neuron disease characterized by vacuolar degeneration of mitochondria. Neuron 1995 14 : 1105 1116.
17. Mackenzie IR, Bigio EH, Ince PG, Geser F, Neumann M, Cairns NJ, Kwong LK, Forman MS, Ravits J, Stewart H, et al. Pathological TDP-43 distinguishes sporadic amyotrophic lateral sclerosis from amyotrophic lateral sclerosis with SOD1 mutations. Ann Neurol 2007 61 : 427 434.
18. Sreedharan J, Blair IP, Tripathi VB, Hu X, Vance C, Rogelj B, Ackerley S, Durnall JC, William KL, Buratti E, et al. TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science 2008 319 : 1668 1672.
19. Tan CF, Eguchi H, Tagawa A, Onodera O, Iwasaki T, Tsujino A, Nishizawa M, Kakita A, Takahashi H. TDP-43 immunoreactivity in neuronal inclusions in familial amyotrophic lateral sclerosis with or without SOD1 gene mutation. Acta Neuropathol 2007 113 : 535 542.
20. Van Deerlin VM, Leverenz JB, Bekris LM, Bird TD, Yuan W, Elman LB, Clay D, Wood EM, Chen-Plotkin AS, Martinez-Lage M, et al. TARDBP mutations in amyotrophic lateral sclerosis with TDP-43 neuropathology: A genetic and histopathological analysis. Lancet Neurol 2008 7 : 409 416.
21. Zelko IN, Mariani TJ, Folz RJ. Superoxide dismutase multigene family: A comparison of the CuZn-SOD (SOD1), Mn-SOD (SOD2), and EC-SOD (SOD3) gene structures, evolution, and expression. Free Radic Biol Med 2002 33 : 337 349.
22. Borchelt DR, Guarnieri M, Wong PC, Lee MK, Slunt HS, Xu ZS, Sisodia SS, Price DL, Cleveland DW. Superoxide dismutase 1 subunits with mutations linked to familial amyotrophic lateral sclerosis do not affect wild-type subunit function. J Biol Chem 1995 270 : 3234 3238.
23. Borchelt DR, Lee MK, Slunt HS, Guarnieri M, Xu ZS, Wong PC, Brown RH Jr., Prize DL, Sisodia SS, Cleveland DW. Superoxide dismutase 1 with mutations linked to familial amyotrophic lateral sclerosis possesses significant activity. Proc Natl Acad Sci U S A 1994 91 : 8292 8296.
24. Bruijn LI, Houseweart MK, Kato S, Anderson KL, Anderson SD, Ohama E, et al. Aggregation and motor neuron toxicity of an ALS-linked SOD1 mutant independent from wild-type SOD1. Science 1998 281 : 1851 1854.
25. Furukawa Y, O'Halloran TV. Posttranslational modifications in Cu,Zn-superoxide dismutase and mutations associated with amyotrophic lateral sclerosis. Antioxid Redox Signal 2006 8 : 847 867.
26. Potter SZ, Valentine JS. The perplexing role of copper-zinc superoxide dismutase in amyotrophic lateral sclerosis (Lou Gehrig's disease). J Biol Inorg Chem 2003 8 : 373 380.
27. Rakhit R, Chakrabartty A. Structure, folding, and misfolding of Cu, Zn superoxide dismutase in amyotrophic lateral sclerosis. Biochim Biophys Acta 2006 1762 : 1025 1037.
28. Valentine JS, Hart PJ. Misfolded CuZnSOD and amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A 2003 100 : 3617 3622.
29. Williamson TL, Corson LB, Huang L, Burlingame A, Liu J, Bruijn LI, Cleveland DW. Toxicity of ALS-linked SOD1 mutants. Science 2000 288 : 399.
30. Wood JD, Beaujeux TP, Shaw PJ. Protein aggregation in motor neurone disorders. Neuropathol Appl Neurobiol 2003 29 : 529 545.
31. Bruijn LI, Cleveland DW. Mechanisms of selective motor neuron death in ALS: Insights from transgenic mouse models of motor neuron disease. Neuropathol Appl Neurobiol 1996 22 : 373 387.
32. Cleveland DW, Bruijn LI, Wong PC, Marszalek JR, Vechio JD, Lee MK, Xu XS, Borchelt DR, Sisodia SS, Price DL. Mechanisms of selective motor neuron death in transgenic mouse models of motor neuron disease. Neurology 1996 47 : S54 S61.
33. Julien JP, Kriz J. Transgenic mouse models of amyotrophic lateral sclerosis. Biochim Biophys Acta 2006 1762 : 1013 1024.
34. Ludolph AC, Meyer T, Riepe MW. The role of excitotoxicity in ALS - what is the evidence? J Neurol 2000 247 (Suppl. 1 I7 16.
35. Przedborski S. Programmed cell death in amyotrophic lateral sclerosis: A mechanism of pathogenic and therapeutic importance. Neurologist 2004 10 : 1 7.
36. Valentine JS. Do oxidatively modified proteins cause ALS? Free Radic Biol Med 2002 33 : 1314 1320.
37. Dupuis L, Gonzalez de Aguilar JL, Oudart H, de TM, Barbeito L, Loeffler JP. Mitochondria in amyotrophic lateral sclerosis: A trigger and a target. Neurodegener Dis 2004 1 : 245 254.
38. Bauer MF, Neupert W. Import of proteins into mitochondria: A novel pathomechanism for progressive neurodegeneration. J Inherit Metab Dis 2001 24 : 166 180.
39. Calabrese V, Lodi R, Tonon C, D'Agata V, Sapienza M, Scapagnini G, Mangiameli A, Pennisi G, Stella AM, Butterfield DA. Oxidative stress, mitochondrial dysfunction and cellular stress response in Friedreich's ataxia. J Neurol Sci 2005 233 : 145 162.
40. Emerit J, Edeas M, Bricaire F. Neurodegenerative diseases and oxidative stress. Biomed Pharmacother 2004 58 : 39 46.
41. Gallaher BW, Hille R, Raile K, Kiess W. Apoptosis: Live or die - hard work either way! Horm Metab Res 2001 33 : 511 519.
42. Gottlieb RA. Mitochondria: Execution central. FEBS Lett 2000 482 : 6 12.
43. Frey TG, Mannella CA. The internal structure of mitochondria. Trends Biochem Sci 2000 25 : 319 324.
44. Lloreta-Trull J, Serrano S. Biology and pathology of the mitochondrion. Ultrastruct Pathol 1998 22 : 357 367.
45. Mannella CA. Structure and dynamics of the mitochondrial inner membrane cristae. Biochim Biophys Acta 2006 1763 : 542 548.
46. Brand MD, Affourtit C, Esteves TC, Green K, Lambert AJ, Miwa S, Pakag JL, Parker N. Mitochondrial superoxide: Production, biological effects, and activation of uncoupling proteins. Free Radic Biol Med 2004 37 : 755 767.
47. Cai J, Yang J, Jones DP. Mitochondrial control of apoptosis: The role of cytochrome c. Biochim Biophys Acta 1998 1366 : 139 149.
48. McBride HM, Neuspiel M, Wasiak S. Mitochondria: More than just a powerhouse. Curr Biol 2006 16 : R551 R560.
49. Sherratt HS. Mitochondria: Structure and function. Rev Neurol (Paris) 1991 147 : 417 430.
50. Chen XJ, Butow RA. The organization and inheritance of the mitochondrial genome. Nat Rev Genet 2005 6 : 815 825.
51. Stuart JA, Brown MF. Mitochondrial DNA maintenance and bioenergetics. Biochim Biophys Acta 2006 1757 : 79 89.
52. Koehler CM. New developments in mitochondrial assembly. Annu Rev Cell Dev Biol 2004 20 : 309 335.
53. Howell N, Elson JL, Chinnery PF, Turnbull DM. mtDNA mutations and common neurodegenerative disorders. Trends Genet 2005 21 : 583 586.
54. Onyango IG, Khan SM. Oxidative stress, mitochondrial dysfunction, and stress signaling in Alzheimer's disease. Curr Alzheimer Res 2006 3 : 339 349.
55. Trushina E, McMurray CT. Oxidative stress and mitochondrial dysfunction in neurodegenerative diseases. Neuroscience 2007 145 : 1233 1248.
56. Xu Z, Jung C, Higgins C, Levine J, Kong J. Mitochondrial degeneration in amyotrophic lateral sclerosis. J Bioenerg Biomembr 2004 36 : 395 399.
57. dam-Vizi V. Production of reactive oxygen species in brain mitochondria: Contribution by electron transport chain and non-electron transport chain sources. Antioxid Redox Signal 2005 7 : 1140 1149.
58. Turrens JF. Mitochondrial formation of reactive oxygen species. J Physiol 2003 552 : 335 344.
59. Chan PH. Mitochondria and neuronal death/survival signaling pathways in cerebral ischemia. Neurochem Res 2004 29 : 1943 1949.
60. Robberecht W. Oxidative stress in amyotrophic lateral sclerosis. J Neurol 2000 247 (Suppl. 1 I1 I6.
61. Bernardi P, Krauskopf A, Basso E, Petronilli V, Blachly-Dyson E, Di LF, Forte MA. The mitochondrial permeability transition from in vitro artifact to disease target. FEBS J 2006 273 : 2077 2099.
62. Crompton M, Virji S, Doyle V, Johnson N, Ward JM. The mitochondrial permeability transition pore. Biochem Soc Symp 1999 66 : 167 179.
63. Halestrap AP, McStay GP, Clarke SJ. The permeability transition pore complex: Another view. Biochimie 2002 84 : 153 166.
64. Javadov S, Karmazyn M. Mitochondrial permeability transition pore opening as an endpoint to initiate cell death and as a putative target for cardioprotection. Cell Physiol Biochem 2007 20 : 1 22.
65. Halestrap AP, Doran E, Gillespie JP, O'Toole A. Mitochondria and cell death. Biochem Soc Trans 2000 28 : 170 177.
66. Andrabi SA, Sayeed I, Siemen D, Wolf G, Horn TF. Direct inhibition of the mitochondrial permeability transition pore: A possible mechanism responsible for anti-apoptotic effects of melatonin. FASEB J 2004 18 : 869 871.
67. De MU, Basso E, Szabo I, Zoratti M. Electrophysiological characterization of the Cyclophilin D-deleted mitochondrial permeability transition pore. Mol Membr Biol 2006 23 : 521 530.
68. Sayeed I, Parvez S, Winkler-Stuck K, Seitz G, Trieu I, Wallesch CW, Schönfeld P, Siemen D. Patch clamp reveals powerful blockade of the mitochondrial permeability transition pore by the D2-receptor agonist pramipexole. FASEB J 2006 20 : 556 558.
69. Bernardi P, Broekemeier KM, Pfeiffer DR. Recent progress on regulation of the mitochondrial permeability transition pore; a cyclosporin-sensitive pore in the inner mitochondrial membrane. J Bioenerg Biomembr 1994 26 : 509 517.
70. Clarkson AN, Sutherland BA, Appleton I. The biology and pathology of hypoxia-ischemia: An update. Arch Immunol Ther Exp (Warsz) 2005 53 : 213 225.
71. Mattson MP, Culmsee C, Yu ZF. Apoptotic and antiapoptotic mechanisms in stroke. Cell Tissue Res 2000 301 : 173 187.
72. Sullivan PG, Rabchevsky AG, Waldmeier PC, Springer JE. Mitochondrial permeability transition in CNS trauma: Cause or effect of neuronal cell death? J Neurosci Res 2005 79 : 231 239.
73. Antonyuk S, Elam JS, Hough MA, Strange RW, Doucette PA, Rodriguez JA, Hayward LJ, Valentine JS, Hart PJ, Hasnain SS. Structural consequences of the familial amyotrophic lateral sclerosis SOD1 mutant His46Arg. Protein Sci 2005 14 : 1201 1213.
74. Furukawa Y, O'Halloran TV. Amyotrophic lateral sclerosis mutations have the greatest destabilizing effect on the apo- and reduced form of SOD1, leading to unfolding and oxidative aggregation. J Biol Chem 2005 280 : 17266 17274.
75. Watanabe M, Dykes-Hoberg M, Culotta VC, Price DL, Wong PC, Rothstein JD. Histological evidence of protein aggregation in mutant SOD1 transgenic mice and in amyotrophic lateral sclerosis neural tissues. Neurobiol Dis 2001 8 : 933 941.
76. Deng HX, Shi Y, Furukawa Y, Zhai H, Fu R, Liu E, Gorrie GH, Khan MS, Hung WY, Bigio EH, et al. Conversion to the amyotrophic lateral sclerosis phenotype is associated with intermolecular linked insoluble aggregates of SOD1 in mitochondria. Proc Natl Acad Sci U S A 2006 103 : 7142 7147.
77. Martin LJ, Chen K, Liu Z. Adult motor neuron apoptosis is mediated by nitric oxide and Fas death receptor linked by DNA damage and p53 activation. J Neurosci 2005 25 : 6449 6459.
78. Hirano A, Nakano I, Kurland LT, Mulder DW, Holley PW, Saccomanno G. Fine structural study of neurofibrillary changes in a family with amyotrophic lateral sclerosis. J Neuropathol Exp Neurol 1984 43 : 471 480.
79. Kusaka H, Hirano A. Fine structure of anterior horns in patients without amyotrophic lateral sclerosis. J Neuropathol Exp Neurol 1985 44 : 430 438.
80. Echaniz-Laguna A, Zoll J, Ponsot E, N'guessan B, Tranchant C, Loeffler JP, Lampert E. Muscular mitochondrial function in amyotrophic lateral sclerosis is progressively altered as the disease develops: A temporal study in man. Exp Neurol 2006 198 : 25 30.
81. Swerdlow RH, Parks JK, Cassarino DS, Trimmer PA, Miller SW, Maguire DJ, Sheehan JP, Maguire RS, Pattee G, Juel VC, et al. Mitochondria in sporadic amyotrophic lateral sclerosis. Exp Neurol 1998 153 : 135 142.
82. Dhaliwal GK, Grewal RP. Mitochondrial DNA deletion mutation levels are elevated in ALS brains. Neuroreport 2000 11 : 2507 2509.
83. Spillane CB, Fletcher NC, Rountree SM, van den BH, Chanduloy S, Morgan JL, Keene FR. Benzothiazole bipyridine complexes of ruthenium(II) with cytotoxic activity. J Biol Inorg Chem 2007 12 : 797 807.
84. Oketani K, Nagakura N, Harada K, Inoue T. In vitro effects of E3040, a dual inhibitor of 5-lipoxygenase and thromboxane A(2) synthetase, on eicosanoid production. Eur J Pharmacol 2001 422 : 209 216.
85. Yildiz-Oren I, Yalcin I, ki-Sener E, Ucarturk N. Synthesis and structure-activity relationships of new antimicrobial active multisubstituted benzazole derivatives. Eur J Med Chem 2004 39 : 291 298.
86. Wahl F, Renou E, Mary V, Stutzmann JM. Riluzole reduces brain lesions and improves neurological function in rats after a traumatic brain injury. Brain Res 1997 756 : 247 255.
87. Plesnila N, von BL, Retiounskaia M, Engel D, Ardeshiri A, Zimmermann R, Hoffmann F, Landshamer S, Wagner E, Culmsee C. Delayed neuronal death after brain trauma involves p53-dependent inhibition of NF-kappaB transcriptional activity. Cell Death Differ 2007 14 : 1529 1541.
88. Klunk WE, Engler H, Nordberg A, Wang Y, Blomqvist G, Holt DP, Bergström M, Savitcheva I, Huang GF, Estrada S, et al. Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound-B. Ann Neurol 2004 55 : 306 319.
89. Heiser V, Engemann S, Brocker W, Dunkel I, Boeddrich A, Waelter S, Nordhoff E, Lurz R, Schugardt N, Rautenberg S, et al. Identification of benzothiazoles as potential polyglutamine aggregation inhibitors of Huntington's disease by using an automated filter retardation assay. Proc Natl Acad Sci U S A 99 Suppl 2002 4 : 16400 16406.
90. Doble A. The pharmacology and mechanism of action of riluzole. Neurology 1996 47 : S233 S241.
91. Hockly E, Tse J, Barker AL, Moolman DL, Beunard JL, Revington AP, Holt K, Sunshine S, Moffitt H, Sathasivam K, et al. Evaluation of the benzothiazole aggregation inhibitors riluzole and PGL-135 as therapeutics for Huntington's disease. Neurobiol Dis 2006 21 : 228 236.
92. Iwasaki Y, Ikeda K, Kinoshita M. Molecular and cellular mechanism of glutamate receptors in relation to amyotrophic lateral sclerosis. Curr Drug Targets CNS Neurol Disord 2002 1 : 511 518.
93. Hebert T, Drapeau P, Pradier L, Dunn RJ. Block of the rat brain IIA sodium channel alpha subunit by the neuroprotective drug riluzole. Mol Pharmacol 1994 45 : 1055 1060.
94. Huang CS, Song JH, Nagata K, Yeh JZ, Narahashi T. Effects of the neuroprotective agent riluzole on the high voltage-activated calcium channels of rat dorsal root ganglion neurons. J Pharmacol Exp Ther 1997 282 : 1280 1290.
95. Mathie A, Veale EL. Therapeutic potential of neuronal two-pore domain potassium-channel modulators. Curr Opin Investig Drugs 2007 8 : 555 562.
96. Song JH, Huang CS, Nagata K, Yeh JZ, Narahashi T. Differential action of riluzole on tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels. J Pharmacol Exp Ther 1997 282 : 707 714.
97. Wang SJ, Wang KY, Wang WC. Mechanisms underlying the riluzole inhibition of glutamate release from rat cerebral cortex nerve terminals (synaptosomes). Neuroscience 2004 125 : 191 201.
98. Wu SN. Large-conductance Ca2+- activated K+ channels:physiological role and pharmacology. Curr Med Chem 2003 10 : 649 661.
99. Xing Y, Zhang Y, Stabernack CR, Eger EI, Gray AT. The use of the potassium channel activator riluzole to test whether potassium channels mediate the capacity of isoflurane to produce immobility. Anesth Analg 2003 97 : 1020 4.
100. Miller RG, Mitchell JD, Lyon M, Moore DH. Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). Cochrane Database Syst Rev CD00(1447), 2007.
101. Schneider CS, Mierau J. Dopamine autoreceptor agonists: Resolution and pharmacological activity of 2,6-diaminotetrahydrobenzothiazole and an aminothiazole analogue of apomorphine. J Med Chem 1987 30 : 494 498.
102. Kreiss DS, Bergstrom DA, Gonzalez AM, Huang KX, Sibley DR, Walters JR. Dopamine receptor agonist potencies for inhibition of cell firing correlate with dopamine D3 receptor binding affinities. Eur J Pharmacol 1995 277 : 209 214.
103. Mierau J, Schneider FJ, Ensinger HA, Chio CL, Lajiness ME, Huff RM. Pramipexole binding and activation of cloned and expressed dopamine D2, D3 and D4 receptors. Eur J Pharmacol 1995 290 : 29 36.
104. Dodson MW, Guo M. Pink1, Parkin, DJ-1 and mitochondrial dysfunction in Parkinson's disease. Curr Opin Neurobiol 2007 17 : 331 337.
105. Schapira AH. Mitochondrial dysfunction in Parkinson's disease. Cell Death Differ 2007 14 : 1261 1266.
106. Chinta SJ, Kumar MJ, Hsu M, Rajagopalan S, Kaur D, Rane A, Nicholls DG, Choi J, Anderson JK. Inducible alterations of glutathione levels in adult dopaminergic midbrain neurons result in nigrostriatal degeneration. J Neurosci 2007 27 : 13997 14006.
107. Hall ED, Andrus PK, Oostveen JA, Althaus JS, VonVoigtlander PF. Neuroprotective effects of the dopamine D2/D3 agonist pramipexole against postischemic or methamphetamine-induced degeneration of nigrostriatal neurons. Brain Res 1996 742 : 80 88.
108. Sethy VH, Wu H, Oostveen JA, Hall ED. Neuroprotective effects of the dopamine agonists pramipexole and bromocriptine in 3-acetylpyridine-treated rats. Brain Res 1997 754 : 181 186.
109. Kakimura J, Kitamura Y, Takata K, Kohno Y, Nomura Y, Taniguchi T. Release and aggregation of cytochrome c and alpha-synuclein are inhibited by the antiparkinsonian drugs, talipexole and pramipexole. Eur J Pharmacol 2001 417 : 59 67.
110. Kitamura Y, Taniguchi T, Shimohama S, Akaike A, Nomura Y. Neuroprotective mechanisms of antiparkinsonian dopamine D2-receptor subfamily agonists. Neurochem Res 2003 28 : 1035 1040.
111. Takata K, Kitamura Y, Kakimura J, Kohno Y, Taniguchi T. Increase of bcl-2 protein in neuronal dendritic processes of cerebral cortex and hippocampus by the antiparkinsonian drugs, talipexole and pramipexole. Brain Res 2000 872 : 236 241.
112. Cassarino DS, Fall CP, Smith TS, Bennett JP Jr. Pramipexole reduces reactive oxygen species production in vivo and in vitro and inhibits the mitochondrial permeability transition produced by the parkinsonian neurotoxin methylpyridinium ion. J Neurochem 1998 71 : 295 301.
113. Fujita Y, Izawa Y, Ali N, Kanematsu Y, Tsuchiya K, Hamano S, Tamaki T, Yoshizumi M. Pramipexole protects against H2O2-induced PC12 cell death. Naunyn Schmiedebergs Arch Pharmacol 2006 372 : 257 266.
114. Le WD, Jankovic J, Xie W, Appel SH. Antioxidant property of pramipexole independent of dopamine receptor activation in neuroprotection. J Neural Transm 2000 107 : 1165 1173.
115. Ramirez AD, Wong SK, Menniti FS. Pramipexole inhibits MPTP toxicity in mice by dopamine D3 receptor dependent and independent mechanisms. Eur J Pharmacol 2003 475 : 29 35.
116. Abramova NA, Cassarino DS, Khan SM, Painter TW, Bennett JP Jr. Inhibition by R(+) or S(-) pramipexole of caspase activation and cell death induced by methylpyridinium ion or beta amyloid peptide in SH-SY5Y neuroblastoma. J Neurosci Res 2002 67 : 494 500.
117. Gu M, Iravani MM, Cooper JM, King D, Jenner P, Schapira AH. Pramipexole protects against apoptotic cell death by non-dopaminergic mechanisms. J Neurochem 2004 91 : 1075 1081.
118. Danzeisen R, Schwalenstoecker B, Gillardon F, Buerger E, Krzykalla V, Klinder K, Schild L, Hengerer B, Ludolph AC, Dorner-Ciossek C, et al. Targeted antioxidative and neuroprotective properties of the dopamine agonist pramipexole and its nondopaminergic enantiomer SND919CL2x [(+)2-amino-4,5,6,7-tetrahydro-6- Lpropylamino-benzathiazole dihydrochloride]. J Pharmacol Exp Ther 2006 316 : 189 199.
119. Wang H, Larriviere KS, Keller KE, Ware KA, Burns TM, Conaway MA, Lacomis D, Pattee GL, Phillips LH, Solenski NJ, et al. R+ pramipexole as a mitochondrially focused neuroprotectant: Initial early phase studies in ALS. Amyotroph Lateral Scler 2008 9 : 50 58.