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Plasma concentrations of endogenous DOPA and 3-O-methyl-DOPA in rats administered benserazide and carbidopa alone or in combination with the reversible COMT inhibitor Ro 41-0960

  • A. Colzi
  • G. Zürcher
  • M. Da Prada
Part of the Key Topics in Brain Research book series (KEYTOPICS)

Summary

In this study in rats the plasma concentration of endogenous 3,4dihydroxyphenyl-l-alanine (DOPA) and 3-O-methyl-DOPA (3-OMD) have been used as a biochemical index to assess the degree of in vivo inhibition of peripheral L-amino acid decarboxylase (AADC) activity after oral benserazide or carbidopa. Benserazide (170 μmoles/kg p.o.) increased the concentration of DOPA and 3-OMD much more efficiently than equimolar doses of carbidopa, showing that benserazide is the most potent of the peripheral AADC inhibitors presently available. The novel reversible catechol-O-methyltransferase (COMT) inhibitor Ro 41-0960 in combination with benserazide was able, by suppressing the formation of 3-OMD, to markedly increase the plasma concentrations of endogenous DOPA. The non-toxic and potent COMT inhibitor Ro 41-0960 might offer therapeutic advantages in the long-term treatment of Parkinson’s disease by substantially improving the DOPA bioavailability of the Madopar-standard or Madopar-HBS formulations.

Keywords

High Performance Liquid Chromatography Glassy Carbon Electrode COMT Inhibitor Equimolar Dose EDTA Disodium 
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

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Copyright information

© Springer-Verlag/Wien 1989

Authors and Affiliations

  • A. Colzi
    • 1
  • G. Zürcher
    • 1
  • M. Da Prada
    • 1
  1. 1.Pharmaceutical Research DepartmentF. Hoffmann-La Roche & Co., Ltd.BasleSwitzerland

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