Modulation of paracetamol antinociception by caffeine and by selective adenosine A2 receptor antagonists in mice

• Published in: European journal of pharmacology 2006-02, Vol.531 (1-3), p.80-86
• Main Authors: GODFREY, Lisa, LUO YAN, CLARKE, Geoffrey D, LEDENT, Catherine, KITCHEN, Ian, HOURANI, Susanna M. O
• Format: Article
• Language: English
• Subjects: Acetaminophen - pharmacology; Adenosine A2 Receptor Antagonists; Analgesics, Non-Narcotic - pharmacology; Animals; Biological and medical sciences; Caffeine - pharmacology; Central Nervous System Stimulants - pharmacology; Dose-Response Relationship, Drug; Female; Male; Medical sciences; Mice; Mice, Knockout; Neuroprotective Agents - pharmacology; Nociceptors - drug effects; Nociceptors - physiopathology; Pain - physiopathology; Pain - prevention & control; Pain Measurement - methods; Pharmacology. Drug treatments; Pyrimidines - pharmacology; Receptor, Adenosine A2A - genetics; Receptor, Adenosine A2A - physiology; Receptor, Adenosine A2B - physiology; Sulfonic Acids - pharmacology; Time Factors; Triazoles - pharmacology; Xanthines - pharmacology
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2005.12.004

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.