5-HT receptor subtypes involved in the spinal antinociceptive effect of acetaminophen in rats.
The present study was designed to investigate which subtype of spinal 5-HT receptors were involved in acetaminophen-induced antinociception using the paw-pressure test. Propacetamol (prodrug of acetaminophen, 400 mg/kg, injected intravenously, corresponding to 200 mg/kg of acetaminophen) produced a significant antinociceptive effect in this test. This effect was at least partially inhibited by intrathecal (i.t.) pretreatment with the 5-HT(1B) (penbutolol), 5-HT(2A) (ketanserin), 5-HT(2C) (mesulergine) receptor antagonists, but not by the 5-HT(1A) (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide trihydrochloride, WAY 100635) and 5-HT(3) (granisetron) receptor antagonists. This profile was very close to that obtained recently with 5-HT, which suggests an implication of 5-HT in the spinal antinociceptive effect of acetaminophen. These results, the lack of binding of acetaminophen to 5-HT receptors and the increase of central 5-HT levels induced by this drug suggest that acetaminophen-induced antinociception could be indirectly mediated by 5-HT.
Courade
J P
JP
Laboratoire de Pharmacologie Médicale, Faculté de Médecine, EMI 9904 INSERM/Université d'Auvergne, BP 38, 30, Place Henri Dunant, 63001 cedex 1, Clermont-Ferrand, France.
Chassaing
C
C
Bardin
L
L
Alloui
A
A
Eschalier
A
A
D000082:Acetaminophen / Q000494:pharmacology*; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D004873:Ergolines / Q000494:pharmacology; D017829:Granisetron / Q000494:pharmacology; D007278:Injections, Spinal; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D017288:Pain Threshold / Q000187:drug effects; D010394:Penbutolol / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044302:Receptor, Serotonin, 5-HT1B; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D044263:Receptors, Serotonin, 5-HT1; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists / Q000494:pharmacology; D013997:Time Factors; D014828:Vocalization, Animal / Q000187:drug effects
D000082:Acetaminophen; D000700:Analgesics; D004873:Ergolines; D017829:Granisetron; D007650:Ketanserin; D010394:Penbutolol; D010879:Piperazines; D011725:Pyridines; D044302:Receptor, Serotonin, 5-HT1B; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; C031649:mesulergine