Skip to main content
SpringerLink
Log in

Neuroprotection and Dopamine Agonists

  • Conference paper
Frontiers in Clinical Neuroscience

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 541))

Abstract

Parkinson’s disease is a neurodegenerative disorder characterized by a progressive loss of the dopaminergic neurons in the substantia nigra pars compacta. Accumulating evidence indicates that apoptosis contributes to the cell death in Parkinson’s disease patients’ brain. Excitotoxicity, oxidative stress, and mitochondrial respiratory failure are thought to be the key inducers of the apoptotic cascade. The chapter will review the evidence suggesting that some agents — and dopamine agonists in particular — are neuroprotective and the possible mechanisms whereby these effects might occur.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Adler, C.H., Sethi, K.D., Hauser, R.A., Davis, T.L., Hammerstad, J.P., Bertoni, J., Taylor, R.L., Sanchez-Ramos, J., and O’Brien, C.F. for the Ropinirole Study Group, 1997, Ropinirole for the treatment of early Parkinson’s disease, Neurology. 49:393–399.

    Google Scholar 

  • Ahlskog, J.E., 2003, Slowing Parkinson’s disease progression: Recent dopamine agonist trials, Neurology. 60:381–389.

    Google Scholar 

  • Appel, S.H., 1981, A unifying hypothesis for the cause of amyotrophic lateral sclerosis, parkinsonism and Alzheimer’s disease, Ann Neurol. 10:499–505.

    Google Scholar 

  • Asanuma, M., Ogawa, N., Nishibayashi, S., Kawai, M., Kondo, Y., and Iwata, E, 1995, Protective effects of pergolide on dopamine levels in the 6-hydroxydopamine-lesioned mouse brain. Arch Int Pharmacodyn Ther. 329:221–230.

    Google Scholar 

  • Ben-Shachar, D., Zuk, R., and Glinka, Y., 1995, Dopamine neurotoxicity: inhibition of mitochondrial respiration, J Neurochem. 64:718–723.

    Google Scholar 

  • Betarbet, R., Sherer, T.B., MacKenzie, G., Garcia-Osuna, M., Panov, A.V., and Greenmyre, J.T., 2000, Chronic systemic pesticide exposure reproduces features of Parkinson’s disease, Nat Neurosci. 3:1301–1306.

    Google Scholar 

  • Blunt, S.B., Jenner, P., and Marsden, C.D., 1993, Suppressive effect of 1-dopa on dopamine cells remaining in the ventral tegmental area of rats previously exposed to the neurotoxin 6-hydroxydopamine, Mov Disord. 8:129–133.

    Google Scholar 

  • Boomsma, F., Meerwaldt, J.D., Man in’t Veld, A.J., Hoverstadt, A., and Schalekamp, M.A., 1989, Treatment of idiopathic parkinsonism with L-dopa in the absence and presence of decarboxylase inhibitors: effects on plasma levels of L-dopa, dopa dexarboxylase, catecholamines and 3-O-methyl-dopa, J Neurol. 236:223–230.

    Google Scholar 

  • Brooks, D.J., 1993, PET studies on the early and differential diagnosis of Parkinson’s disease, Neurology. 43:S6–S16.

    Google Scholar 

  • Carter, A.J., and Mueller, R.E., 1991, Pramipexole, a dopamine D2 receptor agonist, decreases the extracellular concentration of dopamine in vivo, Eur J Pharmacol. 200:65–72.

    Google Scholar 

  • Carvey, P.M., and Ling, Z., 2000, Pramipexole enhances Bcl-xl expression in mesencephalic cultures, Mov Dis. 15 Suppl. 3:17.

    Google Scholar 

  • Cassarino, D.S., Fall, C.P., Smith, T.S., and Bennett, J.P. Jr., 1998, 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. 71:295–301.

    Google Scholar 

  • Cheng, N., Maeda, T., Kume, T., Kaneko, S., Kochiyama, H., Akaike, A., Goshima, Y., and Misu, Y., 1996, Differential neurotoxicity induced by L-DOPA and dopamine in cultured striatal neurons, Brain Res. 16;743:278–283.

    Google Scholar 

  • Cotzias, G. C, Miller, S.T., Tang, L. C, and Papavasiliou, P.S., 1977, Levodopa, fertility, and longevity, Science. 196:549–551.

    Google Scholar 

  • Desagher, S., Glowinski, J., and Premont, J., 1996, Astrocytes protect neurons from hydrogen peroxide toxicity, J Neurosci. 16:2553–2562.

    Google Scholar 

  • Dexter, D.T., Wells, F.R., Agid, F., Less, A.J., Jenner, P., and Marsden, C.D., 1987, Increased iron content in post-mortem parkinsonian brain, Lancet. 2:1219–1220.

    Google Scholar 

  • Dziewczapolski, G., Murer, G., Agid, Y., Gershanik, O., and Raisman-Vozari, R., 1997, Absence of neurotoxicity of chronic L-DOPA in 6-hydroxydopamine-lesioned rats, Neuroreport. 8:975–979.

    Google Scholar 

  • Ferger, B., Teismann, P., and Mierau, J., 2000, The dopamine agonist pramipexole scavenges hydroxyl free radicals induced by striatal application of 6-hydroxydopamine in rats: an in vivo microdialysis study, Brain Res. 883:216–223.

    Google Scholar 

  • Fink, D.J., DeLuca, N.A., Yamada, M., Wolfe, D.P., and Glorioso, J. C, 2000, Design and application of HSV vectors for neuroprotection, Gene Ther. 7:115–119.

    Google Scholar 

  • Finotti, N., Castagna, L., Moretti, A., and Marzatico, F., 2000, Reduction of lipid peroxidation in different rat brain areas after cabergoline treatment, Pharmacol Res. 42:287–291.

    Google Scholar 

  • Frucht, S., Rogers, J.D., Greene, P.E., Gordon, M.F., and Fahn, S., 1999, Falling asleep at the wheel: motor vehicle mishaps in persons taking pramipexole and ropinirole. Neurology. 52:1908–1910.

    Google Scholar 

  • Gassen, M., Glinka, Y., Pinchasi, B., and Youdim, M.B., 1996, Apomorphine is a highly potent free radical scavenger in rat brain mitochondrial fraction, Eur J Pharmacol. 308:219–225.

    Google Scholar 

  • Gassen, M., Gross, A., and Youdim, M.B., 1998, Apomorphine enantiomers protect cultured pheochromocytoma (PC 12) cells from oxidative stress induced by H2O2 and 6-hydroxydopamine, Mov Disord. 13:661–667.

    Google Scholar 

  • Gassen, M., Gross, A., and Youdim, M.B., 1999, Apomorphine, a dopamine receptor agonist with remarkable antioxidant and cytoprotective properties, Adv Neurol. 80:297–302.

    Google Scholar 

  • Gille, G., Rausch, W.D., Hung, S.T., Moldzio, R., Janetzky, B., Hundemer, H.P., Kolter, T., and Reichmann, H., 2002, Pergolide protects dopaminergic neurons in primary culture under stress conditions, J Neural Transm. 109:633–643.

    Google Scholar 

  • Golbe, L.I., Di Iorio, G., Bonavita, V., Miller, D. C, and Duvoisin, R. C, 1990, A large kindred with autosomal dominant Parkinson’s disease, Ann Neurol. 27:276–228.

    Google Scholar 

  • Gomez-Vargas, M., Nishibayashi-Asanuma, S., Asanuma, M., Kondo, Y., Iwata, E., and Ogawa, N., 1998, Pergolide scavenges both hydroxyl and nitric oxide free radicals in vitro and inhibits lipid peroxidation in different regions of the rat brain, Brain Res. 790:202–208.

    Google Scholar 

  • Goshima, Y., Ohno, K., Nakamura, S., Miyamae, T., Misu, Y., and Akaike, A., 1993, L-dopa induces Ca(2+)-dependent and tetrodotoxin-sensitive release of endogenous glutamate from rat striatal slices, Brain Res. 16:167–170.

    Google Scholar 

  • Graham, D.G., 1978, Oxidative pathways for catecholamines in the genesis of neuromelanin and cytotoxic quinones, Mol Pharmacol. 14:633–643.

    Google Scholar 

  • Grunblatt, E., Mandel, S., Berkuzki, T., and Youdim, M.B., 1999, Apomorphine protects against MPTP-induced neurotoxicity in mice, Mov Disord. 14:612–618.

    Google Scholar 

  • Grunblatt, E., Mandel, S., Maor, G., and Youdim, M.B., 2001, Effects of R-and S-apomorphine on MPTP-induced nigro-striatal dopamine neuronal loss, J Neurochem. 77:146–156.

    Google Scholar 

  • Guttman, M., and the International Pramipexole-Bromocriptine Study Group, 1997, Double-blind comparison of pramipexole and bromocriptine treatment with placebo in advanced Parkinson’s disease, Neurology. 49:1060–1065.

    Google Scholar 

  • Hall E.D., Andrus P.K., Oostveen J.A., Althaus J.S., and Von Voigtlander P.F., 1996, Neuroprotective effects of the dopamine D2/D3 agonist pramipexole against postischemic or methamphetamine-induced degeneration of nigrostriatal neurons, Brain Res. 742:80–88.

    Google Scholar 

  • Han, S.K., Mytilineou, C, and Cohen, G., 1996, L-DOPA up-regulates glutathione and protects mesencephalic cultures against oxidative stress, J Neurochem. 66:501–510.

    Google Scholar 

  • Hefti, F., Melamed, E., Bhawan, J., and Wurtman, R, 1981, Long term administration of 1-dopa does not damage dopaminergic neurons in the mouse, Neurology. 31, 1194–1195.

    Google Scholar 

  • Hernan, M.A., Takkouche, B., Caamano-Isorna, F., and Gestal-Otero, J.J., 2002, A meta-analysis of coffee drinking, cigarette smoking, and the risk of Parkinson’s disease, Ann Neurol. 52:276–284.

    Google Scholar 

  • Hirsch, E. C, Hunot, S., Damier, P., and Faucheux, B., 1998, Glial cells and inflammation in Parkinson’s disease: a role in neurodegeneration? Ann Neurol. 44:S115–S120.

    Google Scholar 

  • Homann, C.N., Wenzel, K., Suppan, K., Ivanic, G., Kriechbaum, N., Crevenna, R., and Ott, E., 2002, Sleep attacks in patients taking dopamine agonists: review. BMJ. 324:1483–1487.

    Google Scholar 

  • Hubble, J.P., Koller, W. C, Cutler, N.R., Sramek, J.J., Friedman, J., Goetz, C, Ranhosky, A., Korts, D., and Elvin, A., 1995, Pramipexole in patients with early Parkinson’s disease, Clin Neuropharmacol. 18:338–347.

    Google Scholar 

  • Iida, M., Miyazaki, I., Tanaka, K., Kabuto, H., Iwata-Ichikawa, E., and Ogawa, N., 1999, Dopamine D2 receptor-mediated antioxidant and neuroprotective effects of ropinirole, a dopamine agonist, Brain Res. 838:51–59.

    Google Scholar 

  • Ishikawa, A., and Tsuji, S., 1996, Clinical analysis of 17 patients in 12 Japanese families with autosomal-recessive type juvenile parkinsonism, Neurology. 47:160–166.

    Google Scholar 

  • Iwai, A., Masliah, E., Yoshimoto, M., Ge, N., Flanagan, L., de Silva, H.A., Kittel, A., and Saitoh, T., 1995, The precursor protein of non-A beta component of Alzheimer’s disease amyloid is a presynaptic protein of the central nervous system, Neuron. 14:467–475.

    Google Scholar 

  • Jenner, P., 1991, Oxidative stress as a cause of Parkinson’s disease, Acta Neurol Scand Suppl 136:6–15.

    Google Scholar 

  • Jenner, P., Dexter, D.T., Sian, J., Schapira, A.H. V., and Marsden, C.D., 1992, Oxidative stress as a cause of nigral cell death in Parkinson’s disease and incidental Lewy body disease, Ann Neurol. 32 (Suppl):S82–S87.

    Google Scholar 

  • Kebabian, J.W., and Calne, D.G., 1979, Multiple receptors for dopamine, Nature. 277:93–96.

    Google Scholar 

  • Kimmel, H.L., Yoyce, A.R., Carroll, F.I., and Kuhar, M.J., 2001, Dopamine D1 and D2 receptors influence dopamine transporter synthesis and degradation in the rat, J Pharmacol Exp Ther. 298:129–140.

    Google Scholar 

  • Kitada, T., Asakawa, S., Hattori, N., Matsumine, H., Yamamura, Y., Minoshima, S., Yokochi, M., Mizuno, Y., and Shimizu, N., 1998, Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism, Nature. 392:605–608.

    Google Scholar 

  • Kitamura, Y., Shimohama S., Kamoshima, W., Ota, T., Matsuoka, Y., Nomura, Y., Smith, M.A., Perry, G., Whitehouse, P.J., and Taniguchi, T., 1998, Alterations of proteins regulating apoptosis, Bcl-2, Bcl-x, Bax, Bak, Bad, ICH-I and CPP32, in Alzheimer’s disease. Brain Res. 780:260–269.

    Google Scholar 

  • Kordower, J.H., Emborg, M.E., Bloch, J., Bloch, J., Ma, S.Y., Chu, Y., Leventhal, L., McBride, J., Chen, E. Y., Palfi, S., Roitberg, B.Z., Brown, W.D., Holden, J.E., Pyzalski, R., Taylor, M.D., Carvey, P., Ling, Z., Trono, D., Hantraye, P., Deglon, N., and Aebischer, P., 2000, Neurodegeneration prevented by lentiviral vector delivery of GDNF in primate models of Parkinson’s disease, Science. 290:767–773.

    Google Scholar 

  • Korsching, S., 1993, The neurotrophic factor concept: a reexamination, J Neurosci 13:2739–2748.

    Google Scholar 

  • Kreiss, D.S., Bergstrom, D.A., Gonzalez, A.M., Huang, K.X., Sibley, D.R., and Walters, J.R., 1995, Dopamine receptor agonist potencies for inhibition of cell firing correlate with dopamine D3 receptor binding affinities, Eur J Pharmacol. 227:209–214.

    Google Scholar 

  • Kumar, R., Agarwal, A.K., and Seth, P.K., 1995, Free radical-generated neurotoxicity of 6-hydroxydopamine, J Neurochem. 65:1906.

    Google Scholar 

  • Lee, C.S., Samiiand A., Sossi, V., 2000, In vivo positron emission tomographic evidence for compensatory changes in presynaptic dopaminergic nerve terminals in Parkinson’s disease, Ann Neurol. 47:493–503.

    Google Scholar 

  • Ling, Z.D., Robie, H. C, Tong, C.W., and Carvey, P.M., 1999, Both the antioxidant and D3 agonist actions of pramipexole mediate its neuroprotective actions in mesencephalic cultures. J Pharmacol Exp Ther. 289:203–210.

    Google Scholar 

  • Lieberman, A., Ranhosky, A., and Korts, D., 1997, Clinical evaluation of pramipexole in advanced Parkinson’s disease: results of a double-blind, placebo-controlled, parallel-group study, Neurology. 49:1162–1168.

    Google Scholar 

  • Lieberman, A., Olanow, C.W., Sethi K., Swanson, P., Waters, C.H., Fahn, S., Hurtig, H., Yahr, M., and the Ropinirole Study Group, 1998, A multicenter trial of ropinirole as adjunct treatment for Parkinson’s disease, Neurology. 51:1057–1062.

    Google Scholar 

  • Maier Hoehn, M.M., 1983, Parkinsonism treated with levodopa: progression and mortality, J Neural Transm Suppl. 19:253–264.

    Google Scholar 

  • Masserano, J.M., Gong, L., Kulaga, H., Baker, I., and Wyatt, R.J., 1996, Dopamine induces apoptotic cell death of a catecholaminergic cell line derived from the central nervous system, Mol Pharmacol. 50(5):1309–1315.

    Google Scholar 

  • Matsumine, H., Saito, M., Shimoda-Matsubayashi, S., Tanaka, H., Ishikawa, A., Nakagawa-Hattori, Y., Yokochi, M., Kobayashi, T., Igarashi, S., Takano, H., Sanpei, K., Koike, R., Mori, H., Kondo, T., Mizutani, Y., Schaffer, A.A., Yamamura, Y., Nakamura, S., Kuzuhara, S., Tsuji, S., and Mizuno, Y., 1997, Localization of a gene for an abnormal recessive form of juvenile Parkinsonism to chromosome 6q25. 2-21, Am J Hum Genet. 60:588–596.

    Google Scholar 

  • McGeer, P.L., Itagaki, S., Boyes, B.E., and McGeer, E.G., 1988, Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson’s and Alzheimer’s disease brains, Neurology. 38:1285–1291.

    Google Scholar 

  • Melamed, E., Offen, D., Shirvan, A., Djaldetti, R., Barzilai, A., and Ziv, I., 1998, Levodopa toxicity and apoptosis, Ann Neurol. 44:S149–154.

    Google Scholar 

  • Mena, M.A., Davila, V., and Sulzer, D., 1997, Neurotrophic effects of L-DOPA in postnatal midbrain dopamine neuron/cortical astrocyte cocultures, J Neurochem. 69:1398–1408.

    Google Scholar 

  • Michel, P.P., and Hefti, F., 1990, Toxicity of 6-hydroxydopamine and dopamine for dopaminergic neurons in culture, J Neurosd Res. 26:428–435.

    Google Scholar 

  • Montastruc, J.L., Rascol, O., Senard, J.M., and Rascol, A., 1994, A randomised controlled study comparing bromocriptine to which levodopa was later added, with levodopa alone in previouly untreated patients with Parkinson’s disease: a five year follow-up. J Neurol Neurosurg Psychiatry. 57:1034–1038.

    Google Scholar 

  • Muralikrishnan, D., and Mohanakumar, K.P., 1998, Neuroprotection by bromocriptine against l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine-induced neurotoxicity in mice, FASEB J. 12:905–912

    Google Scholar 

  • Murer, M.G., Dziewczapolski, G., Menalled, L.B., Garcia, M. C,. Agid, Y., Gershanik, O., and Raisman-Vozari, R., 1998, Chronic levodopa is not toxic for remaining dopamine neurons, but instead promotes their recovery, in rats with moderate nigrostriatal lesions, Ann Neurol. 43:561–575.

    Google Scholar 

  • Mytilineou, C, Han, S.K., and Cohen, G., 1993, Toxic and protective effects of L-dopa on mesencephalic cell cultures, J Neurochem. 61:1470–1478.

    Google Scholar 

  • Naoi, M., Dostert, P., Yoshida, M., and Nagatsu, T., N-methylated tetrahydro-isoquinolines as dopaminergic neurotoxins, Adv Neurol 60:212–217.

    Google Scholar 

  • Nishibayashi, S., Asanuma, M., Kohno, M., Gomez-Vargas, M., and Ogawa, N., 1996, Scavenging effects of dopamine agonists on nitric oxide radicals, J Neurochem. 67:2208–2211.

    Google Scholar 

  • Noh, J.S. and Gwag, B.J., 1997, Attenuation of oxidative neuronal necrosis by a dopamine D1 agonist in mouse cortical cell cultures, Exp Neurol. 146:604–608.

    Google Scholar 

  • Offen, D., Ziv, I., Sternin, H., Melamed, E., and Hochman, A., 1996, Prevention of dopamine-induced cell death by thiol antioxidants: possible implications for treatment of Parkinson’s disease, Exp Neurol. 141:32–39.

    Google Scholar 

  • Offen, D., Beart, P.M., Cheung, N.S., Pascoe, C.J., Hochman, A., Gorodin, S., Melamed, E., Bernard, R., and Bernard, O., 1998, Transgenic mice expressing human Bcl-2 in their neurons are resistant to 6-hydroxydopamine and 1-methyl-4-phenyl-l,2,3,6-tetrahydropyridine neurotoxicity, Proc Natl Acad Sci USA. 12:5789–5794.

    Google Scholar 

  • Offen, D., Ziv, I., Panet, H., Wasserman, L., Stein, R., Melamed, E., and Barzilai, A., 1997, Dopamine-induced apoptosis is inhibited in PC12 cells expressing Bcl-2. Cell Mol Neurobiol. 17:289–304.

    Google Scholar 

  • Ogawa, N., Asanuma, M., Kondo, Y., Kawada, Y, Yamamoto, M., and Mori, A., 1994a, Differential effects of chronic 1-DOPA treatment on lipid peroxidation in the mouse brain with and without pretreatment with 6-hydroxydopamine, Neurosci Lett. 171:55–58.

    Article  PubMed  CAS  Google Scholar 

  • Ogawa, N., Tanaka, K., Asanuma, M., Kawai, M., Masumizu, T., Kohno, M., and Mori, A., 1994b, Bromocriptine protects mice against 6-hydroxydopamine and scavenges hydroxyl free radicals in vitro, Brain Res. 657:207–213.

    Google Scholar 

  • Olanow, C.W., Fahn, S., Muenter, M, Klawans, H., Hurtig, H., Stem, M., Shoulson, I., Kurlan, R., Grimes, J. D., Jankovic, J., Hoehn, M., Marham, C.H., Duvoisin, R., Reinmuth, O., Leonard, H.A., Ahlskog, E., Feldman, R., Hershey, L., and Yahr, M.D., 1994, A multi-center, double-blind, placebo-controlled trial of pergolide as an adjunct to sinemet in Parkinson’s disease. Mov Disord. 9:40–47.

    Google Scholar 

  • Olanow, C.V., Hauser R.A., Gauger, L., Malapira, T., Koller, W., Hubble, J., Bushenbark, K., Lilienfeld, D., and Esterlitz, J., 1995, The effect of deprenyl and levodopa on the progression of Parkinson’s disease. Ann Neurol. 38:771–777.

    Google Scholar 

  • Papavasiliou, P.S., Miller, S.T., Thal, L.J., Nerder, L.J., Houlihan, G., Rao, S.N., and Stevens, J.M., 1981, Age-related motor and catecholamine alterations in mice on levodopa supplemented diet, Life Sci. 28:2945–2952.

    Google Scholar 

  • Pardo, B., Mena, M.A., Fahn, S., and De Yebenes, J.G., 1993, Ascorbic acid protects against levodopa-induced neurotoxicity on a catecholamine-rich human neuroblastoma cell line. Mov Disord. 8:278–284.

    Google Scholar 

  • Pardo, B., Mena, M.A., Casarejos, M.J., Paino, C.L., and De Yebenes, J.G., 1995a, Toxic effects of L-DOPA on mesencephalic cell cultures: protection with antioxidants. Brain Res. 5:133–143.

    Google Scholar 

  • Pardo, B., Mena, M.A., and de Yebenes, J.G., 1995b, L-dopa inhibits complex IV of the electron transport chain in catecholamine-rich human neuroblastoma NB69 cells, J Neurochem. 64:576–582.

    Google Scholar 

  • Parkinson, J., 1819, An Essay on the Shaking Palsy, Sherwood, Neely and Jones, London.

    Google Scholar 

  • Parkinson Study Group, 2000, Pramipexole vs levodopa as initial treatment for Parkinson’s disease: A randomised controlled trial, JAMA. 284:1931–1938.

    Google Scholar 

  • Parkinson Study Group, 2002, Dopamine transporter brain imaging to assess the effects of pramipexole vs levodopa on Parkinson disease progression, JAMA. 287:1653–1661.

    Google Scholar 

  • Pelton, E.W. 2nd, Kimelberg, H.K., Shipherd, S.V., and Bourke, R.S., 1981, Dopamine and norepinephrine uptake and metabolism by astroglial cells in culture, Life Sci. 28:1655–1663.

    Google Scholar 

  • Perry, T.L., Young, V.W., Ito, M., Foulks, J.G., Wall, R.A., Godin, D.V., and Clavier, R.M., 1984, Nigrostriatal dopaminergic neurons remain undamaged in rats given high doses of l-dopa and carbidopa chronically, J Neurochem. 43:990–993.

    Google Scholar 

  • Piercey, M.F., Camacho-Ochoa, M., and Smith, M.W., 1995, Functional roles for dopamine-receptor subtypes, Clin Neuropharmacol. 18:34–42.

    Google Scholar 

  • Pinter, M.M., Pogarell, O., and Oertel, W.M., 1999, Efficacy, safety and tolerance of the non-ergoline agonist pramipexole in the treatment of advanced Parkinson’s disease: a double-blind, placebo controlled, randomised, multicentre study, J Neuro Neurosurg Psychiatry. 66:436–441.

    Google Scholar 

  • Polymeropoulos, M.H., Higgins, J.J., Golbe, L.I., Johnson, W.G., Ide, S.E., Di Iorio, G., Sanges, G., Stenroos, E.S., Pho, L.T., Schaffer, A.A., Lazzarini, A.M., Nussbaum, R.L., and Duvoisin, R. C, 1996, Mapping of a gene for Parkinson’s disease to chromosome 4q21-q23, Science. 274:1197–1199.

    Google Scholar 

  • Polymeropoulos, M.H., Lavedan, C, Leroy, E., Ide, S.E., Dehejia, A., Dutra, A., Pike, B., Root, H., Rubenstein, J., Boyer, R., Stenroos, E.S., Chandrasekharappa, S., Athanassiadou, A., Papapetropoulos, T., Johnson, W.G., Lazzarini, A.M., Duvoisin, R. C, Di Iorio, G., Golbe, L.I., and Nussbaum, R.L., 1997, Mutation in the alpha-synuclein gene identified in families with Parkinson’s disease, Science. 276:2045–2047.

    Google Scholar 

  • Pothos, E.N., Przedborski, S., Davila, V., Schmitz, Y., and Sulzer, D., 1998, D2-Like dopamine autoreceptor activation reduces quantal size in PC12 cells, J Neurosci. 18:5575–5585.

    Google Scholar 

  • Przedborski, S., Jackson-Lewis, V., Muthane, U., Jiang, H., Ferreira, M, Naini, A.B., and Fahn, S., 1993, Chronic levodopa administration alters cerebral mitochondrial respiratory chain activity, Ann Neurol. 34:715–723.

    Google Scholar 

  • Przedborski, S., and Jackson-Lewis, V., 1998, Mechanisms of MPTP toxicity., Mov Disord. 13:35–38.

    Google Scholar 

  • Quinn, N., Parkes, J.D., Janota, I., and Marsden, C.D., 1986, Preservation of the substantia nigra and locus coeruleus in a patient receiving levodopa (2 kg) plus decarboxylase inhibitor over a four year period, Mov Disord. 1, 65–68.

    Google Scholar 

  • Rajput, A.H., Fenton, M., Birdi, S., and Macaulay, R., Is levodopa toxic to human substantia nigra? Mov Disord. 12:634–638.

    Google Scholar 

  • Rascol, O., Brooks, D.J., Korczyn, A.D., De Deyn, P.P., Clarke, C.E., and Lang, A.E., for the 056 Study Group, 2000, A five-year study of the incidence of dyskinesia in patients with early Parkinson’s disease who were treated with ropinirole or levodopa, N Engl J Med. 342:1484–1491.

    Google Scholar 

  • Rinne, U.K, 1983, Problems associated with long-term levodopa treatment of Parkinson’s disease, Acta Neurol Scand. 95:19–26.

    Google Scholar 

  • Rioux, L., Frohna, P.A., Joyce, J.N., and Schneider, J.S., 1997, The effects of chronic levodopa treatment on pre-and postsynaptic markers of dopaminergic function in striatum of parkinsonian monkeys, Mov Disord. 12:148–158.

    Google Scholar 

  • Saggu, H., Cooksey, J., Dexter, D., Wells, F.R., Lees, A., Jenner, P., and Marsden, C.D., 1989, A selective increase in particular Superoxide dismutase activity in Parkinson’s substantia nigra, J Neurochem. 53:692–697.

    Google Scholar 

  • Saji, L.M., Blau, A.D., and Volpe, B.T., 1996, Prevention of transneuronal degeneration of neurons in the substantia nigra reticulate by ablation of the subthalamic nucleus, Exp Neurol. 141:120–129.

    Google Scholar 

  • Sampaio-Maia, B., Serrao, M.P., and Soares-Da-Silva, P., 2001, Regulatory path-ways and uptake of l-dopa by capillary cerebral endothelial cells, astrocytes and neuronal cells, Am J Phisiol Cell Physiol. 280:C333–C342.

    Google Scholar 

  • Sanchez-Ramos, J., Overvuk, E., and Ames, B.N., 1994, A marker of oxyradical-mediated DNA damage (8-hydroxy-2’-deoxyguanosine) is increased in nigro-striatum of Parkinson’s disease brain, Neurodegeneration. 3:197–204.

    Google Scholar 

  • Schapira, A.H. V., Cooper, J.M., Dexter, D., Jenner, P., Clark, J.B., and Marsden, C.D., 1989, Mitochondrial complex 1 deficiency in Parkinson’s disease, Lancet. 1:1269.

    Google Scholar 

  • Schapira, A.H. V., 2002a, Neuroprotection and dopamine agonists, Neurology. 58:S9–S18.

    Google Scholar 

  • Schapira, A.H. V., 2002b, Dopamine agonists and neuroprotection in Parkinson’s disease, Eur J Neurol 9:1–6.

    Google Scholar 

  • Schwab, R.S., Amador, L.V., and Levine, J.Y., 1951, Apomorphine in Parkinson’s disease, Trans Am Neurol Assoc. 76:273–279.

    Google Scholar 

  • Schwartz, J. C, Giros, B., Martres, M.P., and Sokoloff, P., 1992. The dopamine receptor family: molecular biology and pharmacology, Semin Neurosci. 4:99–108.

    Google Scholar 

  • Semchuk, K.M., Love, E.J., and Lee, R.G., 1992, Parkinson’s disease and exposure to agriculture work and pesticide chemicals, Neurology. 42:1328–1335.

    Google Scholar 

  • Sethy, V.H., Wu, H., Oostveen, J.A., and Hall, E.D., 1997, Neuroprotective effects of the dopamine agonists pramipexole and bromocriptine in 3-acetylpyridine-treated rats, Brain Res. 754:181–186.

    Google Scholar 

  • Shannon, K.M., Bennett, J.P., and Friedman, J.H., for the Pramipexole Study Group 1997, Efficacy of pramipexole, a novel dopamine agonist, as monotherapy in mild to moderate Parkinson’s disease, Neurology. 49:724–728.

    Google Scholar 

  • Sian, J., Dexter, D.T., Lees, A.J., Daniel, S., Agid, Y., Javoy-Agid, F., Jenner, P., and Marsden, C.D., 1994, Alterations in glutathione levels in Parkinson’s disease and other neurodegenerative disorders affecting basal ganglia, Ann Neurol. 36:348–355.

    Google Scholar 

  • Sotnikova, T.D., Gainetdinov, R.R., Grekhova, T.V., and Rayevsky, K.S., 2001, Effects of intrastriatal infusion of D2 and D3 receptor preferring antagonists on dopamine release in rat dorsal striatum (in vivo microdialysis study), Pharmacol Res. 43:283–290.

    Google Scholar 

  • Spencer, J.P. E., Jenner, A., Aruoma, O.I., Evans, P.J., Kaur, H., Dexter, D.T., Jenner, P., Lees, A.J., Marsden, D.C, and Halliwell, B., 1994, Intense oxidative DNA damage promoted by 1-DOPA and its metabolites: implications for neurodegenerative disease, FEBS Lett. 353:246–250.

    Google Scholar 

  • Spencer-Smith, T., Parker, W.D. Jr, and Bennett, J.P., 1994, L-DOPA increases nigral production of hydroxyl radicals in vivo: potential 1-DOPA toxicity?, NeuroReport. 5:1009–1011.

    Google Scholar 

  • Spina, M.B., and Cohen, G., 1988, Exposure of striatal synaptosomes to levodopa elevates levels of oxidized glutathione, J Pharmacol Exp Ther. 247:502–507.

    Google Scholar 

  • Stocchi, F., Nordera, G., and Marsden, C.D., 1997, Strategies for treating patients with advanced Parkinson’s disease with disastrous fluctuations and dyskinesias, Clin Neuropharmacol. 20:95–115.

    Google Scholar 

  • Tanaka, M., Sotomatsu, A., Kanai, H., and Hirai, S., 1991, Dopa and dopamine cause cultured neuronal death in the presence of iron. J Neurosci. 101.198–203.

    Google Scholar 

  • Tanaka, M., Sotomatsu, A., Kanai, H., and Hirai, S., 1992, Combined histochemical and biochemical demonstration of nigral vulnerability to lipid peroxidation induced by DOPA and iron, Neurosci Lett. 140:42–46.

    Google Scholar 

  • Tanaka, K, Miyazaki, I., Fujita, N., Haque, M.E., Asanuma, M., and Ogawa, N., 2001, Molecular mechanism in activation of glutathione system by ropinirole, a selective dopamine D2 agonist, Neurochem Res. 26:31–36.

    Google Scholar 

  • Takata, K, Kitamura, Y., Kakimura, J., Kohno, Y., and Taniguchi, T., 2000, Increase of bcl-2 protein in neuronal dendritic processes of cerebral cortex and hippocampus by the antiparkinsonian drugs, talipexole and pramipexole, Brain Res. 872:236–241.

    Google Scholar 

  • Tipton, K.F., and Singer, T., 1993, Advances in our understanding of the mechanism of the neurotoxicity of MPTP and related compounds, J Neurochem. 61:1191–1206.

    Google Scholar 

  • Ubeda, A., Montesinos, C, Paya, M., and Alcaraz, M.J., 1993, Iron-reducing and free-radical scavenging properties of apomorphine and some related benzylisoquinolines. Free Radic Biol Med. 15:159–167.

    Google Scholar 

  • Weill, E., 1884, De l’apomorphine dans certains troubles nerveux. Lyon Med. 48:411–419

    Google Scholar 

  • Whone, A.L., Remy, P., Davis, M.R., Sabolek, M., Nahmias, C, A. Stoessl, J., Watts, R.L., and Brooks, D.J., 2002, The REAL-PET study: slower progression in early Parkinson’s disease treated with ropinirole compared with 1-dopa, Neurology. 58:A82–A83.

    Google Scholar 

  • Yee, R.E., Cheng, D.W., Huang, S. C, Namavari, M., Satyamurthy, N., and Barrio, J.R., 2001, Blood-brain barrier neuronal membrane transport of 6-[18F]fluoro-L-DOPA, Biochem Pharmacol. 62:1409–1415.

    Google Scholar 

  • Yoshioka, M., Tanaka, K., Miyazaki, I., Fujita, N., Higashi, Y., Asanuma, M., and Ogawa, N., 2002, The dopamine agonist cabergoline provides neuroprotection by activation of the glutathione system and scavenging free radicals, Neurosci Res. 43:259–267.

    Google Scholar 

  • Youdim, M.B., Gassen, M., Gross, A., Mandel, S., and Grunblatt, E., 2000, Iron chelating, antioxidant and cytoprotective properties of dopamine receptor agonist; apomorphine, J Neural Transm. 58:83–96.

    Google Scholar 

  • Zou, L, Jankovic, J., Rowe, D.B., Xie, W., Appel, S.H., and Le, W., 1999, Neuroprotection by pramipexole against dopamine-and levodopa-induced cytotoxicity, Life Sci. 64:1275–1285.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Centre for Extrapyramidal Disorders, Neurology Hospital, University Medical Centre, SI-1525, Ljubljana, Slovenia

    Zvezdan Pirtošek

  2. Neurology Department, General Hospital, SI-2000, Maribor, Slovenia

    Dušan Flisar

Authors
  1. Zvezdan Pirtošek
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dušan Flisar
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. University of Szeged, Szeged, Hungary

    László Vécsei

Rights and permissions

Reprints and permissions

Copyright information

© 2004 Springer Science+Business Media New York

About this paper

Cite this paper

Pirtošek, Z., Flisar, D. (2004). Neuroprotection and Dopamine Agonists. In: Vécsei, L. (eds) Frontiers in Clinical Neuroscience. Advances in Experimental Medicine and Biology, vol 541. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-8969-7_4

Download citation

  • DOI: https://doi.org/10.1007/978-1-4419-8969-7_4

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-4740-8

  • Online ISBN: 978-1-4419-8969-7

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation