Inhibition of prostaglandin biosynthesis by a new anti-inflammatory drug, TA-60.

Abstract

Effect of a new anti-inflammatory drug which has a little ulcer inducing property on gastrointestinal tract, TA-60 (2-[4-(3-methyl-2-butenyl) phenyl] propionic acid), on the prostaglandin (PG) metabolism was investigated. TA-60 inhibited the PGE2 biosynthesis of the bovine seminal vesicle microsome dose-dependently. The inhibition constant (Ki) of TA-60 was approximately 8 microM. The potency of TA-60 was approximately the same and two times that of ibuprofen (IP) and phenylbutazone (PBZ), respectively. TA-60 did not show the time dependent inhibition of the PGE2 biosynthesis unlikely to indomethacin (IM). The decrease in the PGE2 contents in the stomach of the rats by TA-60 reached a plateau and the content was not decreased to less than a certain level. The PGE2 content of the intestine was not changed by TA-60. TA-60 did not inhibit the activity of the PG degradating enzyme, 15-hydroxy PG dehydrogenase (15-OH-PG-DH) of the gastric mucosa like the other non-steroidal anti-inflammatory drugs (NSAIDs): IP, PBZ and IM. These results suggest that the slight ulcerating effect of TA-60 on the gastrointestinal tract might be resulted from the small decreasing effect of TA-60 on the gastrointestinal level of PGE2.

• Authors: M Muramatsu, M Tanaka, A Fujita, S Otomo, H Aihara, T Amano
• Journal: Journal of pharmacobio-dynamics (J Pharmacobiodyn) Vol. 8 Issue 1 Pg. 11-9 (Jan 1985) ISSN: 0386-846X [Print] Japan
• PMID: 3925113 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents
• Cyclooxygenase Inhibitors
• Phenylpropionates
• Prostaglandins
• Prostaglandins E
• 2-(4-(3-methyl-2-butenyl)phenyl)propionic acid
• Hydroxyprostaglandin Dehydrogenases
• Dinoprostone

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Binding Sites
• Cattle
• Cyclooxygenase Inhibitors
• Depression, Chemical
• Digestive System (analysis, drug effects)
• Dinoprostone
• Hydroxyprostaglandin Dehydrogenases (antagonists & inhibitors)
• Male
• Phenylpropionates (pharmacology)
• Prostaglandins (biosynthesis)
• Prostaglandins E (analysis, biosynthesis)
• Rats
• Stereoisomerism