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

Although acetaminophen is a well established analgesic, its mechanism of ac tion is still unknown. We investigated whether this drug could affect centr al monoaminergic neurotransmission in rats. Significant increases in seroto nin (5-HT) levels were found in the posterior cortex, hypothalamus, striatu m, hippocampus and brain stem, but not spinal cord, 45 min after per os adm inistration of 200-400 mg/kg of acetaminophen. However, this treatment alte red neither the levels of 5-hydroxyindoleacetic acid nor the accumulation o f 5-hydroxytryptophan after blockade of aromatic L-amino acid decarboxylase . On the other hand, a decrease in both the levels of the dopamine (DA) met abolite, dihydroxyphenylacetic acid, and the accumulation of dihydroxypheny lalanine were noted in the striatum of acetaminophen-treated rats. Finally, acetaminophen administration significantly increased noradrenaline (NA) le vels in the posterior cortex. In vitro studies showed that acetaminophen (I mM) enhanced K+-evoked overflow of [H-3]5-HT, but not [H-3]DA and [3H]NA, previously taken up in brain slices, and exerted no direct effect on monoam ine oxidase A, tyrosine hydroxylase and lcatechol-O-methyl-transferase acti vities. These results indicate that acetaminophen affects central monoamine rgic neurotransmission, thereby suggesting that monoamines (especially 5-HT ) might participate in its analgesic action.