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Lamotrigine-antiparkinsonian activity by blockade of glutamate release?

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Journal of Neural Transmission - Parkinson's Disease and Dementia Section

Summary

Recent experiments provide evidence that the NMDA-antagonist MK-801 has a locomotor-stimulating effect in monoamine-depleted rodents. These findings are based upon a hypothetical pathway-circuit including the basal ganglia as a model reflecting hypo- and hyperkinetic movement disorders. We have treated 5 patients suffering from Parkinson's disease with the antiepileptic drug “lamotrigine” which does not appear to be an NMDA-antagonist but acts functionally as a glutamate antagonist by inhibition of presynaptic glutamate release.

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References

  • Albin RL, Young AB, Penney JB (1989) The functional anatomy of basal ganglia disorders. Trends Neurosci 12(10): 366–375

    Article  PubMed  Google Scholar 

  • Albin RL, Makowiec RL, Hollingsworth ZR, Dure IV LS, Penney JB, Young AB (1992) Excitatory amino acid binding sites in the basal ganglia of the rat: a quantitative autoradiographic study. Neuroscience 46(1): 35–48

    Article  PubMed  Google Scholar 

  • Alexander GE, Crutcher MD (1990) Functional architecture of basal ganglia circuits: neural substrates of parallel processing. Trends Neurosci 13(7): 266–271

    Article  PubMed  Google Scholar 

  • Alexander GE, DeLong MR, Strick PL (1986) Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Ann Rev Neurosci 9: 357–381

    Article  PubMed  Google Scholar 

  • Betts T, Goodwin G, Withers RM, Yuen AWC (1991) Human safety of lamotrigine. Epilepsia 32[Suppl 2]: S17-S21

    PubMed  Google Scholar 

  • Binnie CD, Van Emde Boas W, Kasteleijn-Nolste-Trenite DGA, De Korte RA, Merjer JWA Meinardi H, Miller AA, Overweg J, Peck AW, Van Wieringen A, Yuen WC (1986) Acute effects of lamotrigine (BW430C) in persons with epilepsy. Epilepsia 27: 248–254

    PubMed  Google Scholar 

  • Butelman ER (1989) A novel NMDA antagonist, MK-801, impairs performance in a hippocampal-dependent spatial learning task. Pharmacol Biochem Behav 34: 13–16

    Google Scholar 

  • Carlsson M, Carlsson A, (1989a) The NMDA antagonist MK-801 causes marked locomotor stimulation in monoamine-depleted mice. J Neural Transm 75: 221–226

    Article  PubMed  Google Scholar 

  • Carlsson M, Carlsson A (1989b) Dramatic synergism between MK-801 and clonidine with respect to locomotor stimulatory effect in monoamine-depleted mice. J Neural Transm 77: 65–71

    Article  PubMed  Google Scholar 

  • Carlsson M, Carlsson A (1990) Interactions between glutamatergic and monoaminergic systems within the basal ganglia — implications for schizophrenia and Parkinson's disease. Trends Neurosci 13(7): 272–276

    Article  PubMed  Google Scholar 

  • Carlsson M, Svensson A, Carlsson A (1991) Synergistic interactions between muscarinic antagonists, adrenergic agonists and NMDA antagonists with respect to locomotor stimulatory effects in monoamine-depleted mice. Naunyn Schmiedebergs Arch Pharmacol 343(6): 568–573

    Article  PubMed  Google Scholar 

  • Clineschmidt BV, Martin GE, Buntiing PR, Papp NL (1982) Central sympathomimetic activity of (+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5,10-imine (MK-801), a substance with potent anticonvulsant, central sympathomimetic, and apparent anxiolytic properties. Drug Dev Res 2: 135–145

    Article  Google Scholar 

  • Cohen AF, Land GS, Breimer DD, Yuen WC, Winton C, Peck AW (1987) Lamotrigine, a new anticonvulsant: pharmacokinetics in normal humans. Clin Pharmacol Ther 42: 535–541

    PubMed  Google Scholar 

  • DeLong MR (1990) Primate models of movement disorders of basal ganglia origin. Trends Neurosci 13(7): 281–285

    Article  PubMed  Google Scholar 

  • Fauman MA, Fauman BJ (1981) Chronic phencyclidine (PCP) abuse: a psychiatric perspective. In: Domino EF (ed) PCP phencyclidine: historical and current perspectives. NPP Books, Ann Arbor, Michigan, p 419

    Google Scholar 

  • Filion M, Tremblay L, Bédard PJ (1989) Excessive and unselective responses of medial pallidal neurons to both passive movement and striatal stimulation in monkeys with MPTP-induced Parkinsonism. In: Crossman AR, Sambrook MA (eds) Neural mechanisms in disorders of movement. John Libbey, London, pp 157–164

    Google Scholar 

  • Kitai ST, Kita H (1987) Anatomy and physiology of the subthalamic nucleus: a driving force of the basal ganglia. In: Carpenter MB, Jayaraman A (eds) The basal ganglia, vol II. Plenum Press, New York, pp 357–373

    Google Scholar 

  • Klockgether T, Turski L (1989) Excitatory amino acids and the basal ganglia: implications for the therapy of Parkinson's disease. Trends Neurosci 12(8): 285–286

    Article  Google Scholar 

  • Klockgether T, Turski L (1990) NMDA antagonists potentiate antiparkinsonian actions of L-Dopa in monoamine-depleted rats. Ann Neurol 28: 539–546

    Article  PubMed  Google Scholar 

  • Klockgether T, Turski L, Honoré T, Zhang Z, Gash DM, Kurlan R, Greenamyre JT (1991) The AMPA receptor antagonist NBQX has antiparkinsonian effects in monoamine-depleted rats and MPTP-treated monkeys. Ann Neurol 30: 717–723

    Article  PubMed  Google Scholar 

  • Kornhuber J, Bormann J, Retz W, Hübers M, Riederer P (1989) Memantine displaces [H]MK-801 at therapeutic concentrations in postmortem human frontal cortex. Eur J Pharmacol 166: 589–590

    Article  PubMed  Google Scholar 

  • Kornhuber J, Bormann J, Hübers M, Rusche K, Riederer P (1991) Effects of the 1-amino-adamantanes at the MK-801 binding site of the NMDA-receptor-gated ion channel: a human postmortem brain study. Eur J Pharmacol Mol Pharmacol Sect 206: 297–300

    Article  Google Scholar 

  • Leach MJ, Marden CM, Miller AA (1986) Pharmacological studies on lamotrigine, a novel potential antiepileptic drug II. Neurochemical studies on the mechanism of action. Epilepsia 27(5): 490–497

    PubMed  Google Scholar 

  • Leach MJ, Baxter MG, Critchley MAE (1991) Neurochemical and behavioral aspects of lamotrigine. Epilepsia 32[Suppl 2]: S4-S8

    PubMed  Google Scholar 

  • Löschmann P-A, Lange KW, Kunow M, Rettig K-J, Jähnig P, Honoré T, Turski L, Wachtel H, Jenner P, Marsden CD (1991) Synergism of the AMPA-antagonist NBQX and the NMDA-antagonist CPP with L-Dopa in models of Parkinson's disease. J Neural Transm [P-D Sect] 3: 203–213

    Article  Google Scholar 

  • McGeer EG, Zhu SG (1990) Lamotrigine protects against kainate but not ibotenate lesions in rat striatum. Neurosci Lett 112: 348–351

    Article  PubMed  Google Scholar 

  • Miller WC, DeLong M (1987) Altered tonic activity of neurons in the globus pallidus and subthalamic nucleus in the primate MPTP model of parkinsonism. In: Carpenter MB, Jayaraman A (eds) The basal ganglia, vol II. Plenum Press, New York, pp 415–427

    Google Scholar 

  • Miller WC, DeLong M (1988) Parkinsonian symptomatology, an anatomical and physiological analysis. In: Joseph JA (ed) Central determinants of age-related declines in motor function. The New York Academy of Science, New York, pp 287–302

    Google Scholar 

  • Mitchell IJ, Clarke CE, Boyce S, Robertson RG, Peggs D, Sambrook MA, Crossman AR (1989) Neural mechanisms underlying Parkinsonian symptoms based upon regional uptake of 2-deoxyglucose in monkeys exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Neuroscience 32: 213–226

    Article  PubMed  Google Scholar 

  • Morris RGM, Anderson E, Lynch GS, Baudry M (1986) Selective impairment of learning and blockade of long-term potentiation by an N-methyl-D-aspartate receptor antagonist, AP5. Nature 319: 774–776

    Google Scholar 

  • Olney JW, Price MT, Labruyere J, Salles KS, Frierdich G, Mueller M, Silverman E (1987) Antiparkinsonian agents are phencyclidine agonists and N-methyl-aspartate antagonists. Eur J Pharmacol 142: 319–320

    Article  PubMed  Google Scholar 

  • Peck AW (1991) Clinical pharmacology of lamotrigine. Epilepsia 32[Suppl 2]: S9-S12

    PubMed  Google Scholar 

  • Posner J, Holdich T, Crome P (1991) Comparison of lamotrigine pharmacokinetics in young and elderly healthy volunteers. J Pharm Med 1: 121–128

    Google Scholar 

  • Riederer P, Kornhuber J, Gerlach M, Danielczyk W, Youdim MBH (1991) Glutamatergic-dopaminergic imbalance in Parkinson's disease and paranoid hallucinatory psychosis. In: Rinne UK, Nagatsu T, Horowski R (eds) International workshop Berlin, Parkinson's disease. Medicom Europe B. V., Bussum, pp 10–23

    Google Scholar 

  • Rouzaire-Dubois B, Scarnati E (1987a) Increase in glutamate sensitivity of subthalamic nucleus neurons following bilateral decortication: a microiontophoretic study in the rat. Brain Res 403: 366–370

    Article  PubMed  Google Scholar 

  • Rouzaire-Dubois B, Scarnati E (1987b) Pharmacological study of the cortical-induced excitation of subthalamic nucleus neurons in the rat: evidence for amino acids as putative neurotransmiters. Neuroscience 21(2): 429–440

    Article  PubMed  Google Scholar 

  • Turski L (1991) Excitatory amino acid antagonists and Parkinson's disease. In: Rinne UK, Nagatsu T, Horowski R (eds) How to proceed today in treatment. International workshop Berlin Parkinson's Disease. Medicom Europe B. V., Bussum, pp 97–112

    Google Scholar 

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Author notes

  1. P. -A. Fischer

    Present address: Department of Neurology, University of Frankfurt/M., Schleusenweg 2-16, D-W-6000, Frankfurt/M., Federal Republic of Germany

Authors and Affiliations

  1. Department of Neurology, University of Frankfurt/M., Schleusenweg 2-16, D-W-6000, Frankfurt/M., Federal Republic of Germany

    F. Zipp & H. Baas

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  1. F. Zipp
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  2. H. Baas
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  3. P. -A. Fischer
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Zipp, F., Baas, H. & Fischer, P.A. Lamotrigine-antiparkinsonian activity by blockade of glutamate release?. J Neural Transm Gen Sect 5, 67–75 (1993). https://doi.org/10.1007/BF02260916

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  • DOI: https://doi.org/10.1007/BF02260916

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