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Effects of L-deprenyl and amantadine in an MPTP-model of parkinsonism

  • W.-D. Rausch
  • E. Schallauer
  • W. W. Chan
  • P. Riederer
  • M. Weiser
Conference paper
Part of the Journal of Neural Transmission book series (NEURAL SUPPL, volume 32)

Summary

Mongolian gerbils of both sexes received a single daily dose of 40mg/kg of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) over 4 consecutive days. On the fifth day the animals were treated with 15mg/kg i.p. of L-deprenyl or amantadine or the combination of both drugs. At different time intervals (1, 2, 5 hours) the animals were sacrificed. In the caudate nuclei dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) were measured by an HPLC technique.

MPTP affected the dopaminergic (HVA -25%) as well as the serotoninergic system (5-HT -54%, 5-HIAA -31%). l-deprenyl and amantadine accumulated DA and 5-HT in the MPTP affected caudates. Synergistic effects of the drug combination could be proven.

Keywords

Vanillic Acid Mongolian Gerbil Single Daily Dose Monotherapy Group Serotoninergic System 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Adams JD, Kalivas PW, Miller CA (1989) The acute histopathology of MPTP in the mouse CNS. Brain Res Bull 23:1–17.PubMedCrossRefGoogle Scholar
  2. Albin RL, Young AB, Penney JB (1989) The functional anatomy of basal ganglia. Trends Neurosci 12:366–375.PubMedCrossRefGoogle Scholar
  3. Carlsson M, Carlsson A (1989) The NMDA antagonist MK-801 causes marked locomotor stimulation in monoamine-depleted mice. J Neural Transm 75:221–226.PubMedCrossRefGoogle Scholar
  4. Chiueh CC, Burns RS, Markey SP, Jacobowitz DM, Kopin IJ (1985) Primate model of Parkinsonism: selective lesion of nigrostriatal neurons by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine produces an extrapyramidal syndrome in rhesus monkeys. Life Sci 36:213–218.PubMedCrossRefGoogle Scholar
  5. Cohen G, Pasik, P, Cohen B, Leist A, Mytilineou C, Yahr MD (1985) Pargyline and deprenyl prevent the neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in monkeys. Eur J Pharmacol 106:209–210.CrossRefGoogle Scholar
  6. Hallman H, Lange J, Olson L, Stromberg I, Jonsson G (1985) Neurochemical and histochemical characterization of neurotoxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine on brain catecholamine neurons in the mouse. J Neurochem 44:117–127.PubMedCrossRefGoogle Scholar
  7. Kornhuber J, Bormann J, Retz W, Hübers M, Riederer P (1989) Memantine displaces (3H) MK-801 at therapeutic concentrations in postmortem human frontal cortex. Eur J Pharmacol 166:589–590.PubMedCrossRefGoogle Scholar
  8. Maj J, Sowinska H, Baran L (1972) The effect of amantadine on motor activity and catalepsy in rats. Psychopharmacologia 24:296–307.PubMedCrossRefGoogle Scholar
  9. Parkes JD, Zilkha KJ, Calver DM, Knill-Jones RP (1970) Controlled trial of amantadine hydrochloride in Parkinson’s disease. Lancet i:259–262.CrossRefGoogle Scholar
  10. Sperk G (1982) Simultaneous determination of serotonin, 5-HIAA, DOPAC and HVA with ECD. J Neurochem 38:840–843.PubMedCrossRefGoogle Scholar
  11. Wesemann W, Ekenna O (1982) Effect of 1-aminoadamantanes on the MAO activity in brain, liver and kidney of the Tat. Arzneimittelforschung/Drug Res 32:1241–1243.Google Scholar

Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • W.-D. Rausch
    • 1
  • E. Schallauer
    • 1
  • W. W. Chan
    • 1
  • P. Riederer
    • 2
  • M. Weiser
    • 1
  1. 1.Institute for Medical ChemistryVeterinary Medical University ViennaViennaAustria
  2. 2.Clinical Neurochemistry, Department of PsychiatryUniversity of Würzburg, School of MedicineWürzburgFederal Republic of Germany

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