Clinical efficacy of budipine in Parkinson’s disease

  • H. Przuntek
  • T. Müller
Part of the Journal of Neural Transmission. Supplementa book series (NEURAL SUPPL, volume 56)


The lipophilic t-butyl analog of 1-alkyl-4,4-diphenyl piperidine, budipine, possesses a polyvalent spectrum of mechanisms of action. Budipine experimentally increased the brain content of norepinephrine, serotonine, dopamine and histamine in reserpine treated rats. Budipine did not alter the receptor affinity of these neurotransmitters but antagonizes the effect of NMDA at its receptor binding site in vitro. Budipine reduced MPP+ toxicity in the nigrostriatal system of mice. This complex pharmacologic profile is not comparable to the one of convenient antiparkinsonian drugs. In clinical trials budipine reduced tremor, akinesia and rigidity. Budipine induced a relevant additional positve effect in patients with an optimal dopaminergic therapy based on levodopa and dopamine agonists, such as bromocriptine. Current available data suggest that the need for levodopa application in early stages of the disease may be postponed by budipine and that the long-term application of budipine may induce a levodopa-sparing effect.


NMDA Receptor Dopamine Agonist Receptor Binding Site Anti Parkinsonian Drug Dopamine Deficit 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Bonnet AM, Loria Y, Saint Hilaire MH, Lhermitte F, Agid Y (1987) Does long-term aggravation of Parkinson’s disease result from nondopaminergic lesions? Neurology 37: 1539–1542PubMedCrossRefGoogle Scholar
  2. Braak H, Braak E, Yilmazer D, de Vos RAI, Jansen ENH (1995) Nigral and extranigral pathology in Parkinson’s disease. J Neural Transm [Suppl] 46: 15–32Google Scholar
  3. Chase TN, Engber TM, Mouradian MM (1996) Contribution of dopaminergic and glutaminergic mechanisms to the pathogenesis of motor response complications. Adv Neurol 69: 497–501PubMedGoogle Scholar
  4. Fahn S (1996) Is Levodopa toxic? Neurology 47 Suppl 3: 184–195CrossRefGoogle Scholar
  5. Fahn S (1997) Levodopa-induced neurotoxicity: does it represent a problem for the treatment of Parkinson’s disease? CNS Drugs 8(5): 376–393CrossRefGoogle Scholar
  6. Hacknack G, Menge HG, Eistetter K, Krüger U, Schäefer H, Klosa J (1979) 4,4-Diphenylpiperidine-ein neuer Substanztyp für die Therapie des Morbus Parkinson. Österr Chemie Z 4: 61–62Google Scholar
  7. Jackisch R, Huang HY, Reimann W, Limberger N (1993) Effects of the antiparkinsonian drug budipine on neurotransmitter release in central nervous system tissue in vitro. J Pharmacol Exp Ther 264: 889–898PubMedGoogle Scholar
  8. Jackisch R, Kruchen A, Sauermann W, Hertting G, Feuerstein TJ (1994) The antiparkinsonian drugs budipine and biperiden are use-dependent (uncompetitive) NMDA receptor antagonists. Eur J Pharmacol 264: 207–211PubMedCrossRefGoogle Scholar
  9. Jellinger K (1999) Post mortem studies in Parkinson’s disease — is it possible to detect brain areas for specific symptoms? J Neural Transm [Suppl] 56: 1–29CrossRefGoogle Scholar
  10. Jellinger K, Bliesath H (1987) Adjuvant treatment of Parksinson’s disease with budipine: a double-blind trial versus placebo. J Neurol 234: 280–282PubMedCrossRefGoogle Scholar
  11. Klockgether T, Jacobsen P, Loschmann PA, Turski L (1993) The antiparkinsonian agent budipine is an N-methyl-D-aspartate antagonist. J Neural Transm [PD-Sect] 5: 101–106CrossRefGoogle Scholar
  12. Kornhuber J, Herr B, Thome J, Riederer P (1995) The antiparkinsonian drug budipine binds to NMDA and sigma receptors in post mortem brain tissue. J Neural Transm [Suppl] 46: 131–137Google Scholar
  13. Menge H, Brand U (1982) Zusammenfassende Darstellung der Pharmakologie von Budipin, einem neuen 4,4 Diphenylpiperidinderivat für die Parkinson-Therapie. Drug Res 32: 85–98Google Scholar
  14. Menge HG, Brand U (1985) Pharmacologic bases of antiparkinsonian therapy. In: Gerstenbrand F, Poewe W, Stern G. (eds) Clinical experiences with budipine in Parkinson therapy. Springer, Berlin Heidelberg New York Tokyo, pp 82–92CrossRefGoogle Scholar
  15. Mihatsch W, Russ H, Przuntek H (1988) Intracerebroventricular administration of 1-methyl-4-phenylpyridinium ion in mice: effects of simultaneously administered nomifensine, deprenyl, and 1-t-butyl-4. 4-diphenylpiperidine. J Neural Transm 71: 177–188PubMedCrossRefGoogle Scholar
  16. Niznik HB, Tyndale RF, Sallee FR, Gonzales FJ, Hardwick JP, Inaba T, Kalow W (1990) The dopamine transporter and cytochrome P450IID1 (debrisoquine 4-hydroxylase) in brain: resolution and identification of two distinct (3H)GBR-12935 binding proteins. Arch Biochem Biophys 276: 424–432PubMedCrossRefGoogle Scholar
  17. Przuntek H, Russ H (1985) Budipine and the MPTP binding site. Lancet 2: 35–36PubMedCrossRefGoogle Scholar
  18. Przuntek H, Stasch JP (1984) Biochemical and pharmacologic aspects of the mechanism of action of budipine. In: Gerstenbrand F, Poewe W, Stern G. (eds) Clinical experiences with budipine in Parkinson therapy. Springer, Berlin Heidelberg New York Tokyo, pp 106–111Google Scholar
  19. Przuntek H, Russ H, Henning K, Pindur U (1985) The protective effect of 1-tert. butyl-4,4-diphenylpiperidine against the nigrostriatal neurodegeneration caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Life Sci 37: 1195–1200PubMedCrossRefGoogle Scholar
  20. Russ H, Pindur U, Przuntek H (1986) The interaction of 1-alkyl-4. 4-diphenylpiperidines with the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine receptor binding site. J Neural Transm 65: 157–166PubMedCrossRefGoogle Scholar
  21. Schaefer H, Hackmack G, Eistetter K, Kruger U, Menge HG, Klosa J (1984) Synthesis, physical-chemical properties and pharmacologically-oriented screening studies on budipine and related 4,4-diphenylpiperidines. Arzneimittelforschung 34: 233–240PubMedGoogle Scholar
  22. Siegfried J, Fischer R (1985) Budipine: A new chemical substance in the treatment of Parkinson’s disease. In: Gerstenbrand F, Poewe W, Stern G (eds) Clinical experiences with budipine in Parkinson therapy. Springer, Berlin Heidelberg New York Tokyo, pp 153–157Google Scholar
  23. Spieker S, Löschmann P, Jentges C. Boose A. Klockgether T, Dichgans J (1995) Tremorlytic activity of budipine: a quantitative study with long-term tremor recordings. Clin Neuropharmacol 18(3): 266–272PubMedCrossRefGoogle Scholar
  24. Spieker S, Breit S, Klockgether T, Dichgans J (1999) Tremorlytic activity of budipine in Parkinson’s disease. J Neural Transm [Suppl] 56: 165–172CrossRefGoogle Scholar
  25. Stasch JP, Russ H, Schacht U, Witteler M, Neuser D, Gerlach M, Leven M, Kuhn W, Jutzi P, Przuntek H (1988) 4,4-Diphenylpiperidine derivates and their sila analogues. A comparative study of their interaction with neural receptor binding sites and synaptosomal monoamine uptake. Arzneimittelforschung 38: 1075–1078PubMedGoogle Scholar
  26. Verhagen Metman L, Del Dotto P, van den Munckhof BS, Fang J, Mouradian MM, Chase TN (1998) Amantadine as treatment for dyskinesias and motor fluctuations in Parkinson’s disease. Neurology 50: 1323–1326PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 1999

Authors and Affiliations

  • H. Przuntek
    • 1
  • T. Müller
    • 1
  1. 1.Department of NeurologyRuhr University of BochumBochumFederal Republic of Germany

Personalised recommendations