Acetaminophen-induced antinociception via central 5-HT2A receptors

Effect of acute and repeated administration of paracetamol on opioidergic and serotonergic systems in rats

“…Our data indicate a difference in the effect of paracetamol and morphine on non-infl ammatory pain after repeated administrations, since morphine lost its analgesic effect while paracetamol maintained it, as also described by other authors [24]. In this experimental model both morphine and paracetamol exerted their analgesic effect without affecting motor activity.…”

Effects of acetaminophen on monoaminergic systems in the rat central nervous system

“…Therefore, possible changes in 5-HT release/reuptake might have actually accounted for the increased brain levels of the indoleamine in acetaminophen-treated rats. In line with this hypothesis, a decreased density of cortical 5-HT 2A receptor binding sites has been reported in rats treated acutely with acetaminophen (Pini et al 1996;Srikiatkhachorn et al 1999), possibly reflecting a receptor down-regulation in response to excessive stimulation by elevated levels of extracellular 5-HT. Using in vitro conditions, we presently found that acetaminophen increased K + -evoked [ 3 H]5-HT overflow from slices of the posterior cortex.…”

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

“…Although other studies have reported the effect of high doses of paracetamol (400 mg/kg) (Pini et al, 1996;Srikiatkhachorn et al, 1999;Sandrini et al, 2001;Bonnefont et al, 2003), we did not study doses above 200 mg/kg because of the known toxic effects (Tee et al, 1987;Gardner et al, 2002). Caffeine at a dose of 40 mg/kg has previously been shown to have an antinociceptive effect in the hot plate test when combined with paracetamol (Engelhardt et al, 1997).…”