Abstract
Long-term nonsteroidal anti-inflammatory drugs (NSAIDs) therapy has been associated with several adverse effects such as gastric ulceration and cardiovascular events. Among the molecular modifications strategies, the prodrug approach is a useful tool to discover new safe NSAIDs. The 1-(2,6-dichlorophenyl)indolin-2-one is a diclofenac prodrug which demonstrated relevant anti-inflammatory properties without gastro ulceration effect. In addition, the prodrug decreases PGE(2) levels, COX-2 expression and cellular influx into peritoneal cavity induced by carrageenan treatment. Preliminary pharmacokinetic studies have shown in vivo bioconversion of prodrug to diclofenac. This prodrug is a new nonulcerogenic NSAID useful to treat inflammatory events by long-term therapy.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Anti-Inflammatory Agents, Non-Steroidal / adverse effects
-
Anti-Inflammatory Agents, Non-Steroidal / chemistry
-
Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics
-
Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
-
Carrageenan / adverse effects
-
Cyclooxygenase 2 / genetics
-
Cyclooxygenase 2 / metabolism
-
Diclofenac / administration & dosage
-
Diclofenac / adverse effects
-
Diclofenac / analogs & derivatives
-
Diclofenac / chemistry
-
Diclofenac / pharmacokinetics
-
Diclofenac / pharmacology*
-
Dinoprostone / biosynthesis
-
Disease Models, Animal
-
Edema / chemically induced
-
Edema / drug therapy
-
Leukocytes / metabolism
-
Male
-
Mice
-
Molecular Structure
-
Peritoneal Cavity / pathology
-
Prodrugs*
-
Rats
-
Stomach Ulcer / chemically induced
Substances
-
Anti-Inflammatory Agents, Non-Steroidal
-
Prodrugs
-
Diclofenac
-
Carrageenan
-
Cyclooxygenase 2
-
Dinoprostone
-
lumiracoxib