Modulation of catecholamine release from rat striatal slices by the fixed combination of aspirin, paracetamol and caffeine

Autor: Ravi Shankar Akundi, Günter Finkenzeller, Bernhard Aicher, Eduardo Candelario-Jalil, Michela Mantovani, Peter Dr. Schnierle, Michael Hüll, Rainer Knörle, Bernd L. Fiebich, Marcus Heinzmann
Rok vydání: 2006
Předmět:
Zdroj: Pharmacological Research. 53:391-396
ISSN: 1043-6618
DOI: 10.1016/j.phrs.2006.02.002
Popis: The fixed combination of aspirin, paracetamol (acetaminophen) and caffeine has been used successfully to treat different kinds of pain including migraine attacks. Even when this formulation has been marketed for a long time, the exact molecular mechanisms underlying its therapeutic effectiveness have not been completely elucidated. In the present investigation, we have studied the effects of the fixed combination of aspirin, paracetamol and caffeine (APC) on the release of dopamine and noradrenaline from rat striatal slices in an attempt to find potential new mechanisms of action of this widely used analgesic combination. We found that APC produced a significant reduction in extracellular dopamine and a dramatic increase in norepinephrine release from the slices incubated with different concentrations of APC (dose relationship 1:1:0.2, corresponding to the dose-relationship of Thomapyrin®). These findings suggest that the modulation of catecholaminergic neurotransmission is a new pharmacological effect of APC which could explain the mechanism of action of this formulation, considering that the independent effect of either compound alone does not explain the potent antinociceptive properties when observed in combination.
Databáze: OpenAIRE