Advertisement

Sparteine oxidation in patients with early- and late-onset of Parkinson’s disease

  • K. Chiba
  • H. Imai
  • H. Yoshino
  • J. Kato
  • T. Ishizaki
  • H. Narabayashi
Conference paper
Part of the Key Topics in Brain Research book series (KEYTOPICS)

Summary

We studied the oxidation of sparteine in 36 patients with early onset (onset of age <50 years) and 36 patients with late onset (onset of age ⩾50 years) of Parkinson’s disease. The results were compared with those obtained from 84 healthy volunteers. Although no poor metabolizer was found in the patients with Parkinson’s disease, there was an inverse and significant (P < 0.01) relationship between the onset of age and log metabolic ratio (MR) of sparteine (Spearman’s rs = -0.431). The mean (±S.D.) MR value (1.52 ± 1.40) of the patients with early onset was significantly (P < 0.01) higher than, whereas that (0.81 ±0.99) of the patients with late onset was not significantly different from, that (0.62 ±0.62) of the control subjects with extensive metabolizer phenotype. The mean greater MR value found in the patients with early onset of Parkinson’s disease was derived mainly from the more frequency of patients with relatively greater MR value for phenotyping extensive metabolizers (MR > 1.5). These findings indicate that the oxidative capacity of sparteine is not defective but reduced in some patients with an earlier onset of Parkinson’s disease, possibly implying that the decreased activity of cytochrome P-450 responsible for the oxidation of sparteine would be a factor to accelerate the onset of the Parkinson’s disease.

Keywords

Late Onset Metabolic Ratio Antihistamine Drug Polymorphic Oxidation Sparteine Oxidation 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Barbeau A, Cloutier T, Roy M, Plasse L, Paris S, Poirier J (1985) Ecogenetics of Parkinson’s disease: 4-hydroxylation of debrisoquine. Lancet ii: 1213–1216Google Scholar
  2. Benitez J, Ladero JM, Jimenez-Jimenez FJ, Martinez C, Puerto AM, Valdivielso MJ, Llerena A, Cobaleda J, Munoz JJ (1990) Oxidative polymorphism of debrisoquine in Parkinson’s disease. J Neurol Neurosurg Psychiatry 53: 289–292PubMedCrossRefGoogle Scholar
  3. Brosen K (1990) Recent developments in hepatic drug oxidation. Implications for clinical pharmacokinetics. Clin Pharmacokinet 18: 220–239PubMedCrossRefGoogle Scholar
  4. Horii H, Kubota E, Ishizaki T, Kato Y (1990) Effects of N-methylmer- captoimidazole 011 the disposition of MPTP and its metabolites in mice. Eur J Pharmacol 180: 59–67PubMedCrossRefGoogle Scholar
  5. Chiba K, Kato J, Hashimoto K, Ishizaki T (1988a) Apparent Mendelian recessive inheritance of sparteine metabolism in an extended Japanese family. Eur J Clin Pharmacol 34: 661–662PubMedCrossRefGoogle Scholar
  6. Chiba K, Kubota E, Miyakawa T, Kato Y, Ishizaki T (1988b) Characterization of hepatic microsomal metabolism as an in vivo detoxication pathway of l-methyl-4- phenyl-1,2,3,6-tetrahydropyridine in mice. J Pharmacol Exp Ther 246: 1108–1115PubMedGoogle Scholar
  7. Eichelbaum M, Bertilson L, Sawe J, Zekorn C (1982) Polymorphic oxidation of sparteine and debrisoquine: related pharmacogenetic entities. Clin Pharmacol Ther 31: 184–186PubMedCrossRefGoogle Scholar
  8. Eichelbaum M, Gross S (1990) The genetic polymorphism of debrisoquine/sparteine metabolism - clinical aspects. Pharmacol Ther 46: 377–394PubMedCrossRefGoogle Scholar
  9. Fonne-Pfister R, Meyer UA (1988) Xenobiotic and endobiotic inhibitors of cytochrome P-450 dbl function, the target of the debrisoquine/sparteine type polymorphism. Biochem Pharmacol 37: 3829–3835PubMedCrossRefGoogle Scholar
  10. Gudjonsson O, Sanz E, Alvan G, Aquilonius S-M, Reviriego J (1989) Poor hydroxylator phenotypes of debrisoquine and S-mephenytoin are not over-represented in a group of patients with Parkinson’s disease. Br J Pharmacol 30: 301–302Google Scholar
  11. Ishizaki T, Eichelbaum M, Horai Y, Hashimoto K, Chiba K, Dengler HJ (1987) Evidence for polymorphic oxidation of sparteine in Japanese subjects. Br J Clin Pharmacol 23: 482–48PubMedGoogle Scholar
  12. Kondo D, Kurland LT, Schull WJ (1973) Parkinson’s disease: genetic analysis and evidence of a multifactorial etiology. Mayo Clin Proc 48: 465–475PubMedGoogle Scholar
  13. Langston JW, Irwin I (1986) MPTP: current concepts and controversies. Clin Neuro pharmacol 9: 487–507Google Scholar
  14. Makino Y, Ohta S, Tachikawa O, Hirobe M (1988) Presence of tetrahydroisoquinoline and 1-methyl-tetrahydro-isoquinoline in foods: compounds related to Parkinson’s disease. Life Sci 43: 373–378PubMedCrossRefGoogle Scholar
  15. Marsden CD (1990) Parkinson’s disease. Lancet i: 948–952Google Scholar
  16. Nagatsu T, Yoshida M (1988) An endogenous substance of the brain, tetrahydro-isoquinoline, produces parkinsonism in primates with decreased dopamine, tyrosine hydroxylase and biopterin in the nigrostriatal regions. Neurosci Lett 87: 178–182PubMedCrossRefGoogle Scholar
  17. Ohta S, Tachikawa O, Makino Y, Tasaki Y, Hirobe M (1990) Metabolism and brain accumulation of tetrahydroisoquinoline (TIQ). A possible parkinsonism inducing substance, in an animal model of a poor debrisoquine metabolizer. Life Sci 46: 599–606Google Scholar
  18. Poirier J, Roy M, Campanella G, Cloutier T, Paris S (1987) Debrisoquine metabolism in Parkinsonian patients treated with antihistamine drugs. Lancet ii: 386Google Scholar
  19. Steventon GB, Heafield MTH, Waring RH, Williams AC (1989) Xenobiotic metabolism in Parkinson’s disease. Neurology 39: 883–887PubMedGoogle Scholar
  20. Yokochi M, Narabayashi H (1981) Clinical characteristics of juvenile parkinsonism. In: Rose FC, Capildeo R (eds) Research progress in Parkinson’s disease. Pitman Medical, Tunbridge Wells, Kent, pp 35–39Google Scholar

Copyright information

© Springer-Verlag/Wien 1991

Authors and Affiliations

  • K. Chiba
    • 1
  • H. Imai
    • 2
  • H. Yoshino
    • 2
  • J. Kato
    • 1
  • T. Ishizaki
    • 1
  • H. Narabayashi
    • 2
  1. 1.Division of Clinical Pharmacology, Clinical Research InstituteNational Medical CenterShinjuku-ku, Tokyo 162Japan
  2. 2.Department of NeurologyJuntendo University School of MedicineTokyoJapan

Personalised recommendations