Antinociceptive effects of oral clonidine and S12813-4 in acute colon inflammation in rats.
Acute colonic inflammation was induced by perendoscopic injection of 50 microleters of dilute formalin (5%) in the depth of the colonic wall (c.w.) in rats. Compared to saline injection, the procedure was followed by nociceptive behaviors from which visceral nociception was quantified. The alpha 2-adrenoceptor agonist, clonidine 2-[2,6-dichlorophenylamine]-2-imidazole hydrochloride (75, 150 and 300 mg/kg), administered orally 15 min after c.w. injection of formalin significantly reduced the nociceptive responses at the high dose only. However, when administered 30 min prior to nociceptive stimulation, the compound exhibited an antinociceptive effect at the three doses. A novel analgesic, the compound "S12813-4' 3-[2-(4-phenylpiperazine-1-yl)-ethyl]-2-oxo-2,3-dihydro-oxazolo[b] pyridine, chlorydrate (10, 30 and 90 mg/kg), given orally displayed antinociceptive effects whatever the administration schedule, before or after c.w. injection of formalin. The antinociceptive effect of S12813-4 (30 mg/kg given orally) was prevented by subcutaneous (s.c.) injection of yohimbine or idazoxan (1 mg/kg). We conclude that visceral nociception elicited by formalin-induced colonic inflammation is attenuated by clonidine and S12813-4. The pharmacological profiles of the two compounds and the inhibition of the antinociceptive effect of S12813-4 by yohimbine and idazoxan suggest that noradrenergic mechanisms are involved in the transmission and/or modulation of the nociceptive influx arising from the inflamed colon.
Miampamba
M
M
Institut National de la Santé et de la Recherche Médicale, Hôpital Edouard Herriot, Lyon, France.
Chéry-Croze
S
S
Détolle-Sarbach
S
S
Guez
D
D
Chayvialle
J A
JA
D000208:Acute Disease; D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D003000:Clonidine / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy*; D005260:Female; D005557:Formaldehyde / Q000633:toxicity; D019329:Idazoxan / Q000494:pharmacology; D010080:Oxazoles / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015016:Yohimbine / Q000494:pharmacology
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D010080:Oxazoles; C088312:S 12813; D005557:Formaldehyde; D015016:Yohimbine; D003000:Clonidine; D019329:Idazoxan