The antinociceptive effect induced by FR140423 is mediated through spinal 5-HT2A and 5-HT3 receptors.
The involvement of 5-HT receptors in the antinociceptive effect of FR140423, 3-(difluoromethyl)-1-(4-methoxyphenyl)-5-[4-(methylsulfinyl)phenyl]py razole, was investigated in mice by means of the tail-pinch test. The antinociceptive effect of FR140423 injected i.t. was completely abolished by co-administration of the non-selective serotonin (5-hydroxytryptamine, 5-HT) receptor antagonist methysergide, the 5-HT2A receptor antagonist ketanserin and the 5-HT3 receptor antagonist MDL-72222 (3-tropanyl-3,5-dichlorobenzoate) but not by the 5-HT2B receptor antagonist SB-204741 (N-(1-methyl-5-indolyl)-N'-(3-methylisothiazol-5-yl)urea) or the 5-HT2C receptor antagonist SB-242084 (6-chloro-5-methyl-N-[6-(2-methylpyridin-3-yloxy)pyridin-3-y l]indolin e-1-carboxamine). The antinociceptive effect of FR140423 administered orally was abolished by i.t., but not by i.c.v., injection of methysergide, ketanserin and MDL-72222. These data indicate that FR140423, unlike morphine, exerts its antinociceptive effect against a mechanical noxious stimulus, such as in the tail-pinch test, by activation of spinal 5-HT2A and 5-HT3 receptors.
Ochi
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Department of Immunology and Inflammation, Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., 1-6, Kashima 2-chome, Yodogawa, Osaka 532-8514, Japan. takehiro_ochi@po.fujisawa.co.jp
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D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D051379:Mice; D010146:Pain / Q000503:physiopathology / Q000517:prevention & control; D010147:Pain Measurement / Q000379:methods; D010879:Piperazines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology*; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D044406:Receptors, Serotonin, 5-HT3; D012701:Serotonin / Q000031:analogs & derivatives* / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D013454:Sulfoxides; D014326:Tropanes / Q000494:pharmacology
D000700:Analgesics; D010879:Piperazines; D011720:Pyrazoles; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013454:Sulfoxides; D014326:Tropanes; C108904:3-(difluoromethyl)-1-(4-methoxyphenyl)-5-(4-(methylsulfinyl)phenyl)pyrazole; C042390:alpha-methylserotonin; D012701:Serotonin; C040083:1-(2-methoxyphenyl)piperazine; D007650:Ketanserin; C042253:bemesetron; D008784:Methysergide