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. 1969 May;36(1):107–115. doi: 10.1111/j.1476-5381.1969.tb08308.x

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

G F Murphy, D Robinson, D F Sharman
PMCID: PMC1703540  PMID: 5768081

Abstract

1. 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-dihydroxyphenylalanine or probenecid.

2. 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.

3. 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.

4. 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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ANDEN N. E., ROOS B. E., WERDINIUS B. On the occurrence of homovanillic acid in brain and cerebrospinal fluid and its determination by a fluorometric method. Life Sci. 1963 Jul;(7):448–458. doi: 10.1016/0024-3205(63)90132-2. [DOI] [PubMed] [Google Scholar]
  2. BELLEAU B., BURBA J. OCCUPANCY OF ADRENERGIC RECEPTORS AND INHIBITION OF CATECHOL O-METHYL TRANSFERASE BY TROPOLONES. J Med Chem. 1963 Nov;6:755–759. doi: 10.1021/jm00342a028. [DOI] [PubMed] [Google Scholar]
  3. BELLEAU B., BURBA J. Tropolones: a unique class of potent non-competitive inhibitors of S-adenosylmethionine-catechol methyltransferase. Biochim Biophys Acta. 1961 Nov 25;54:195–196. doi: 10.1016/0006-3002(61)90956-8. [DOI] [PubMed] [Google Scholar]
  4. DE VALK A. T., Jr, PRICE H. L. The chemical estimation of epinephrine and norepinephrine in human and canine plasma. I. A critique of the ethylenediamine condensation method. J Clin Invest. 1956 Aug;35(8):837–841. doi: 10.1172/JCI103337. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. GOLDSTEIN M. CEREBRAL METABOLISM OF DOPA-C14 IN RATS. Int J Neuropharmacol. 1964 Apr;3:37–43. doi: 10.1016/0028-3908(64)90043-7. [DOI] [PubMed] [Google Scholar]
  6. ROSS S. B., HALJASMAA O. CATECHOL-O-METHYL TRANSFERASE INHIBITORS. IN VIVO INHIBITION IN MICE. Acta Pharmacol Toxicol (Copenh) 1964;21:215–225. doi: 10.1111/j.1600-0773.1964.tb01786.x. [DOI] [PubMed] [Google Scholar]
  7. ROSS S. B., HALJASMAA O. CATECHOL-OMETHYL TRANSFERASE INHIBITORS. IN VITRO INHIBITION OF THE ENZYME IN MOUSE-BRAIN EXTRACT. Acta Pharmacol Toxicol (Copenh) 1964;21:205–214. doi: 10.1111/j.1600-0773.1964.tb01785.x. [DOI] [PubMed] [Google Scholar]
  8. Sharman D. F. Changes in the metabolism of 3,4-dihydroxyphenylethylamine (dopamine) in the striatum of the mouse induced by drugs. Br J Pharmacol Chemother. 1966 Nov;28(2):153–163. doi: 10.1111/j.1476-5381.1966.tb01881.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Sharman D. F., Poirier L. J., Murphy G. F., Sourkes T. L. Homovanillic acid and dihydroxyphenylacetic acid in the striatum of monkeys with brain lesions. Can J Physiol Pharmacol. 1967 Jan;45(1):57–62. doi: 10.1139/y67-006. [DOI] [PubMed] [Google Scholar]

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