Possible Interaction: Amitriptyline and Caffeine

“Adenosine A(1) receptor interactions are worthy of attention, as chronic oral caffeine (0.1, 0.3g/L, doses considered relevant to human intake levels) blocked antinociception by systemic amitriptyline in normal mice.”

“Low doses of caffeine given systemically inhibit antinociception by several analgesics (acetaminophen, amitriptyline , oxcarbazepine, cizolirtine), probably reflecting block of a component of action involving adenosine A(1) receptors.”

“Following systemic administration, caffeine reversed the systemic effect of amitriptyline in wild type, but not A1R -/- mice; -/+ mice exhibited an intermediate effect.”

“Intraplantar administration of caffeine also reversed the effect of intraplantar amitriptyline in A1R +/+, but not in -/- or +/- mice.”

“The results of this study … that chronic administration of amitriptyline is effective in alleviating thermal hyperalgesia, but not static tactile allodynia, in the hindpaw ipsilateral to nerve injury, and the block of this effect by caffeine suggests that this effect is partially achieved through manipulation of endogenous adenosine systems.”

“ Amitriptyline showed distinct inhibition of 3-N- and 1-N-demethylation of caffeine , though its effect was less potent than in the case of imipramine (Ki = 57 and 61 pM, respectively).”

“… amitriptyline on 8-hydroxylation and … 7-N-demethylation of caffeine was weaker (Ki = 108 and 190 pM, respectively) than on 3-N- or 1-N-demethylation, suggesting a narrower spectrum … P-450 inhibition by amitriptyline than by imipramine, involving mainly the subfamily CYP1A2, and--to a lesser degree--CYP3A.”

“Coadministration of caffeine (1500 nmol) partially antagonized the effects of both doses of amitriptyline.”

“Systemic administration of caffeine (1.5-7.5 mg/kg), at the same time as amitriptyline, blocked the thermal antihyperalgesic effect of 10 mg/kg amitriptyline.”

“This involvement is important in light of the widespread consumption of caffeine , which may potentially act to reduce the benefits of amitriptyline in the treatment of neuropathic pain.”

“Coadministration of caffeine with amitriptyline partially reversed the antinociceptive action of amitriptyline against both behaviours at 2.5% formalin.”