Summary
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.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
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: 1539–1542
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: 15–32
Chase TN, Engber TM, Mouradian MM (1996) Contribution of dopaminergic and glutaminergic mechanisms to the pathogenesis of motor response complications. Adv Neurol 69: 497–501
Fahn S (1996) Is Levodopa toxic? Neurology 47 Suppl 3: 184–195
Fahn S (1997) Levodopa-induced neurotoxicity: does it represent a problem for the treatment of Parkinson’s disease? CNS Drugs 8(5): 376–393
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: 61–62
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: 889–898
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: 207–211
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: 1–29
Jellinger K, Bliesath H (1987) Adjuvant treatment of Parksinson’s disease with budipine: a double-blind trial versus placebo. J Neurol 234: 280–282
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: 101–106
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: 131–137
Menge H, Brand U (1982) Zusammenfassende Darstellung der Pharmakologie von Budipin, einem neuen 4,4 Diphenylpiperidinderivat für die Parkinson-Therapie. Drug Res 32: 85–98
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 82–92
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: 177–188
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: 424–432
Przuntek H, Russ H (1985) Budipine and the MPTP binding site. Lancet 2: 35–36
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 106–111
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: 1195–1200
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: 157–166
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: 233–240
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 153–157
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): 266–272
Spieker S, Breit S, Klockgether T, Dichgans J (1999) Tremorlytic activity of budipine in Parkinson’s disease. J Neural Transm [Suppl] 56: 165–172
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: 1075–1078
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: 1323–1326
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1999 Springer-Verlag Wien
About this paper
Cite this paper
Przuntek, H., Müller, T. (1999). Clinical efficacy of budipine in Parkinson’s disease. In: Przuntek, H., Müller, T. (eds) Diagnosis and Treatment of Parkinson’s Disease — State of the Art. Journal of Neural Transmission. Supplementa, vol 56. Springer, Vienna. https://doi.org/10.1007/978-3-7091-6360-3_3
Download citation
DOI: https://doi.org/10.1007/978-3-7091-6360-3_3
Publisher Name: Springer, Vienna
Print ISBN: 978-3-211-83275-2
Online ISBN: 978-3-7091-6360-3
eBook Packages: Springer Book Archive