[Inhibition of aromatic amino acid decarboxylases by the anti-inflammatory agent flobufen and 2',4'-difluorbiphenyl-4-acetic acid].
The effect of the novel Czechoslovak antiphlogistic agent flobufen (VUFB 16066, 4-[2',4'-difluorbiphenyl]-4-oxo-methyl-butanic acid) and its metabolite 2',4'-difluorbiphenyl-4-yl acetic acid (VUFB 17203) on decarboxylase of aromatic amino acids (DAAK, E. C. 4.1.1.28) of the rat liver (supernatant 20,000 x g) was studied in vitro. The concentrations of 3.8 x 10(-4) mol x 1(-1) of flobufen and 4.4 x 10(-4) mol x 1(-1) of difluorbiphenylyl acetic acid produced 50% inhibition n the enzyme. Ki for flobufen is approximately 1.5 x 10(-4) mol x 1(-1), the reaction with the inhibitor takes place in the ratio 1:1 and the enzyme-inhibitor complex does not exert any catalytic activity. In the tissues with a low activity of DAAK, inhibition could be manifested by decreased synthesis of serotonin and dopamine.
Drsata
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J
Pribová
M
M
Hais
I M
IM
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism; D001713:Biphenyl Compounds / Q000494:pharmacology*; D002087:Butyrates / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008099:Liver / Q000201:enzymology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D000894:Anti-Inflammatory Agents, Non-Steroidal; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D001713:Biphenyl Compounds; D002087:Butyrates; C056474:flobufen; C064102:2',4'-difluorobiphenyl-4-acetic acid; D001142:Aromatic-L-Amino-Acid Decarboxylases
Inhibice dekarboxylázy aromatických aminokyselin protizánĕtlivými látkami flobufenem a kyselinou 2',4'-difluorbifenyl-4-yloctovou.