Abstract
We previously proposed that membrane permeabilization activity of NSAIDs is involved in NSAID-induced gastric lesions. We here synthesized derivatives of loxoprofen that have lower membrane permeabilization activity than other NSAIDs. Compared to loxoprofen, the derivatives 10a and 10b have lower membrane permeabilization activity and their oral administration produced fewer gastric lesions but showed an equivalent anti-inflammatory effect. These results suggest that 10a and 10b are likely to be therapeutically beneficial as safer NSAIDs.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Administration, Oral
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Animals
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Anti-Inflammatory Agents, Non-Steroidal / adverse effects
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Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis*
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Anti-Inflammatory Agents, Non-Steroidal / chemistry
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Cell Membrane Permeability
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Cyclooxygenase Inhibitors / adverse effects
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Cyclooxygenase Inhibitors / chemical synthesis
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Cyclooxygenase Inhibitors / pharmacology
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Gastric Mucosa / drug effects*
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Gastric Mucosa / pathology
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Gastrointestinal Hemorrhage / chemically induced
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Gastrointestinal Hemorrhage / pathology
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Humans
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Phenylpropionates / adverse effects
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Phenylpropionates / chemical synthesis*
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Phenylpropionates / pharmacology
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Prodrugs / adverse effects
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Prodrugs / chemical synthesis*
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Prodrugs / pharmacology
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Rats
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Structure-Activity Relationship
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Cyclooxygenase Inhibitors
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Phenylpropionates
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Prodrugs
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loxoprofen