Modulation of paracetamol antinociception by caffeine and by selective adenosine A2 receptor antagonists in mice.
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.
Godfrey
Lisa
L
Pharmacology Group, School of Biomedical and Molecular Sciences, University of Surrey, Guildford, Surrey GU2 7XH, UK.
Yan
Luo
L
Clarke
Geoffrey D
GD
Ledent
Catherine
C
Kitchen
Ian
I
Hourani
Susanna M O
SM
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
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