Abstract
Oxidative phosphorylation (expressed as ADP/O ratio) in liver mitochondria of rats was uncoupled by 2-amino-3-ethoxycarbonyl-6-benzyl-4, 5, 6, 7-tetrahydrothieno [2, 3-c] pyridine (Y-3642) hydrochloride in vitro. The concentration of 20% inhibition of the compound was about 90 μM, which is lower than that of acetylsalicylic acid or Ibufenac, but higher than that of phenylbutazone, Indomethacin, or flufenamic acid. The ADP/O ratio of the mitochondria obtained from rats after oral administration of Y-3642 in a dose of 100 mg/kg was not different from that of untreated control. Y-3642 showed a reverse action on mitochondria swelling ; it promoted at 1000 μM and inhibited the swelling at 500 μM. Activation of mitochondria ATPase in the presence of Y-3642 at a concentration of 100 μM was only 12%, against 227% at 5 μM of flufenamic acid. These results may suggest that Y-3642 produces a functional change in the mitochondria without a structural change and that production or hydrolysis of ATP does not play an important role in the mechanism of anti-inflammatory activity of this compound.
