title: Modulation of paracetamol antinociception by caffeine and by selective adenosine A2 receptor antagonists in mice.
abstract: This study investigated the involvement of adenosine receptors in the interaction between paracetamol and caffeine in mice, using the adenosine A2A receptor antagonist 5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine (SCH58261) and the adenosine A2B receptor antagonist 1-propyl-8-p-sulfophenylxanthine (PSB1115), in the tail immersion and hot-plate tests. Paracetamol (10-200 mg/kg) was antinociceptive in both tests, but, in contrast to previous studies, caffeine (10 mg/kg) was pronociceptive in the tail immersion test, and reduced the effects of paracetamol in both tests. SCH58261 (3 mg/kg) was antinociceptive in both tests and in its presence paracetamol (50 mg/kg) had no further effect. PSB1115 (10 mg/kg) had little effect alone but potentiated the effect of paracetamol (50 mg/kg) in the hot-plate test and abolished it in the tail immersion test. These results suggest that adenosine A2B receptors may be involved in the action of paracetamol in a pathway-dependent manner, and also support the existence of pronociceptive adenosine A2A receptors.
authors.affiliation: Pharmacology Group, School of Biomedical and Molecular Sciences, University of Surrey, Guildford, Surrey GU2 7XH, UK.
authors.forename: Lisa
authors.initials: L
authors.lastname: Godfrey
authors.forename: Luo
authors.initials: L
authors.lastname: Yan
authors.forename: Geoffrey D
authors.initials: GD
authors.lastname: Clarke
authors.forename: Catherine
authors.initials: C
authors.lastname: Ledent
authors.forename: Ian
authors.initials: I
authors.lastname: Kitchen
authors.forename: Susanna M O
authors.initials: SM
authors.lastname: Hourani
mesh_terms: D000082:Acetaminophen / Q000494:pharmacology*; D058917:Adenosine A2 Receptor Antagonists; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018696:Neuroprotective Agents / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects* / Q000503:physiopathology; D010146:Pain / Q000503:physiopathology / Q000517:prevention & control; D010147:Pain Measurement / Q000379:methods; D011743:Pyrimidines / Q000494:pharmacology*; D043705:Receptor, Adenosine A2A / Q000235:genetics / Q000502:physiology; D043704:Receptor, Adenosine A2B / Q000502:physiology; D013451:Sulfonic Acids / Q000494:pharmacology; D013997:Time Factors; D014230:Triazoles / Q000494:pharmacology*; D014970:Xanthines / Q000494:pharmacology
chemical_list: C098657:5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine; D058917:Adenosine A2 Receptor Antagonists; D018712:Analgesics, Non-Narcotic; D000697:Central Nervous System Stimulants; D018696:Neuroprotective Agents; D011743:Pyrimidines; D043705:Receptor, Adenosine A2A; D043704:Receptor, Adenosine A2B; D013451:Sulfonic Acids; D014230:Triazoles; D014970:Xanthines; D000082:Acetaminophen; D002110:Caffeine