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