Different modes of inhibition of rat gastric mucosal 6-keto-PGF1 alpha production by indomethacin, aspirin and aminopyrine.
The actions of aminopyrine on rat gastric mucosal cyclooxygenase activity in vitro were investigated and compared with those of the cyclooxygenase inhibitors indomethacin and aspirin. Aminopyrine is a phenyl-pyrazolone derivative with potent analgesic and antipyretic properties, but is weakly ulcerogenic, while indomethacin and aspirin are known to cause considerable ulcerogenesis. Aminopyrine was less potent in its ability to inhibit cyclooxygenase activity. The inhibition by all three drugs decreased with an increase in the substrate concentration. Pre-incubation with the enzymes greatly increased the inhibitory action of indomethacin and aspirin, but only slightly increased that of aminopyrine. The inhibitory action of aminopyrine was reversible, whereas those of indomethacin and aspirin were irreversible. These findings are discussed in relation to the low incidence of gastrointestinal irritation caused by aminopyrine.
Nishikawa
T
T
Department of Pharmacology Kagoshima University Dental School, Japan.
Tomori
Y
Y
Yamashita
S
S
Shimizu
S
S
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis*; D000632:Aminopyrine / Q000494:pharmacology*; D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors; D005753:Gastric Mucosa / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D016861:Cyclooxygenase Inhibitors; D000632:Aminopyrine; D015121:6-Ketoprostaglandin F1 alpha; D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin; D007213:Indomethacin