Effects of acetaminophen on monoaminergic systems in the rat central nervous system.
Although acetaminophen is a well established analgesic, its mechanism of action is still unknown. We investigated whether this drug could affect central monoaminergic neurotransmission in rats. Significant increases in serotonin (5-HT) levels were found in the posterior cortex, hypothalamus, striatum, hippocampus and brain stem, but not spinal cord, 45 min after per os administration of 200-400 mg/kg of acetaminophen. However, this treatment altered neither the levels of 5-hydroxyindoleacetic acid nor the accumulation of 5-hydroxytryptophan after blockade of aromatic L-amino acid decarboxylase. On the other hand, a decrease in both the levels of the dopamine (DA) metabolite, dihydroxyphenylacetic acid, and the accumulation of dihydroxyphenylalanine were noted in the striatum of acetaminophen-treated rats. Finally, acetaminophen administration significantly increased noradrenaline (NA) levels in the posterior cortex. In vitro studies showed that acetaminophen (1 mM) enhanced K+-evoked overflow of [3H]5-HT, but not [3H]DA and [3H]NA, previously taken up in brain slices, and exerted no direct effect on monoamine oxidase A, tyrosine hydroxylase and catechol-O-methyl-transferase activities. These results indicate that acetaminophen affects central monoaminergic neurotransmission, thereby suggesting that monoamines (especially 5-HT) might participate in its analgesic action.
Courade
J P
JP
UPSA Laboratoires (Bristol-Myers Squibb group), Paris La Defense, France.
Caussade
F
F
Martin
K
K
Besse
D
D
Delchambre
C
C
Hanoun
N
N
Hamon
M
M
Eschalier
A
A
Cloarec
A
A
D000082:Acetaminophen / Q000008:administration & dosage / Q000494:pharmacology*; D000284:Administration, Oral; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism* / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000096:biosynthesis / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D015854:Up-Regulation / Q000187:drug effects
D018712:Analgesics, Non-Narcotic; D015306:Biogenic Monoamines; D012701:Serotonin; D000082:Acetaminophen; D004298:Dopamine; D009638:Norepinephrine