The effect of tropolone on the formation of 3,4‐dihydroxyphenylacetic acid and 4‐hydroxy‐3‐methoxyphenylacetic acid in the brain of the mouse

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Abstract
The development of a very sensitive and specific fluorimetric assay for 3,4‐dihydroxyphenylacetic acid has made it possible to measure how inhibitors of the enzyme catechol‐O‐methyl transferase affect the relative concentrations of this acid and its O‐methylated derivative 4‐hydroxy‐3‐methoxyphenylacetic acid (homovanillic acid) in the brains of mice treated with l‐3,4‐dihydroxy‐phenylalanine or probenecid. It was found that tropolone and tropolone‐4‐acetamide reduce the concentration of homovanillic acid in the brains of the treated mice to an extent dependent on the dose. The concentration of 3,4‐dihydroxyphenylacetic acid in the brain was increased by the administration of tropolone or tropolone‐4‐acetamide but the dose and response were not simply related to one another. The results suggest that, in vivo, the formation of 3,4‐dihydroxyphenylacetic acid is not always a simple alternative to the formation of homovanillic acid when the enzyme catechol‐O‐methyl transferase is inhibited.