Potent analgesic and anti-inflammatory activities of 1-furan-2-yl-3-pyridin-2-yl-propenone with gastric ulcer sparing effect.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most frequently prescribed drug for the treatment of inflammation and pain. However, conventional NSAIDs and selective COX-2 inhibitors have shown many side effects such as gastric mucosal damage and cardiovascular problems. Recently, the use of dual acting inhibitors of cyclooxygenases (COX) and lipoxygenase (LOX) has been highlighted for their minimized side effects compared to NSAIDs. The objective of the present study was to examine the efficacy and the gastric side effects of 1-furan-2-yl-3-pyridin-2-yl-propenone (FPP-3), a synthetic dual inhibitor of COX/5-LOX. Indomethacin (1-50 mg/kg, p.o.), a non-selective COX inhibitor, and FPP-3 (0.5-50 mg/kg, p.o.), a dual inhibitor, significantly suppressed the carrageen-induced paw edema with different pharmacological profiles. The concentrations of FPP-3 and indomethacin showing 50% inhibition of the maximum paw edema in rats were 10 mg/kg and 20 mg/kg, respectively. More importantly, there were no gastric ulcers formed in FPP-3-treated rats and mice, whereas indomethacin caused gastric mucosal bleeding in a concentration-dependent manner. In addition, FPP-3 showed an analgesic effect in acetic acid-induced writhing response in mice in a dose-dependent manner. The results suggest that FPP-3 may have a benefit in combatting inflammation and pain by dual inhibition of COX and LOX.
Lee
Eung-Seok
ES
College of Pharmacy, Yeungnam University, 214-1 Dae-dong, Gyeongsan 712-749, Korea.
Park
Byung Chul
BC
Paek
Seung-Hwan
SH
Lee
Yoon-Seok
YS
Basnet
Arjun
A
Jin
Da-Qing
DQ
Choi
Han-Gon
HG
Yong
Chul Soon
CS
Kim
Jung-Ae
JA
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004487:Edema / Q000188:drug therapy; D005663:Furans / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D051379:Mice; D008813:Mice, Inbred ICR; D011407:Propane / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D011725:Pyridines / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000473:pathology
C508534:1-furan-2-yl-3-pyridin-2-yl-propenone; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D005663:Furans; D011725:Pyridines; D011407:Propane