Effects of URB597, an inhibitor of fatty acid amide hydrolase (FAAH), on analgesic activity of paracetamol
Language English Country Sweden Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
20802454
PII: NEL310410A10
Knihovny.cz E-resources
- MeSH
- Amidohydrolases antagonists & inhibitors MeSH
- Benzamides pharmacology MeSH
- Carbamates pharmacology MeSH
- Drug Interactions MeSH
- Linear Models MeSH
- Pain Measurement drug effects MeSH
- Mice MeSH
- Analgesics, Non-Narcotic pharmacology MeSH
- Acetaminophen pharmacology MeSH
- Dose-Response Relationship, Drug MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Amidohydrolases MeSH
- Benzamides MeSH
- cyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl ester MeSH Browser
- fatty-acid amide hydrolase MeSH Browser
- Carbamates MeSH
- Analgesics, Non-Narcotic MeSH
- Acetaminophen MeSH
OBJECTIVES: Paracetamol is converted to an active metabolite AM404 via fatty acid amide hydrolase (FAAH). The aim of the present study was to ascertain whether a FAAH inhibitor URB597 antagonizes paracetamol analgesic activity (and to asses by this way the role of FAAH in analgesic activity of paracetamol). METHODS: The interaction between a FAAH inhibitor URB597 and paracetamol was investigated in the writhing test in mice using an isobolographic analysis. RESULTS: URB597 or paracetamol alone and in combinations produced dose-dependent antinociceptive effects. ED50 values were estimated for the individual drugs and an isobologram was constructed. The observed ED50 value for the URB57-paracetamol combination was 0.097 (0.062-0.247) mg/kg. This value did not differ significantly from the theoretical additive ED50 value for the URB597-paracetamol combination which was 0.108 (0.059-0.198) mg/kg. Thus, inhibition of FAAH by URB597 was not followed by the lack of analgesic activity in paracetamol. CONCLUSION: The present results suggest that the analgesic activity of paracetamol is not dependent solely on FAAH metabolic conversion to AM404 and that paracetamol exerts analgesic activity also by additional mechanisms.
