FR143166 attenuates spinal pain transmission through activation of the serotonergic system.
We investigated the antinociceptive effect of 1-(4-fluorophenyl)-3-methyl-5-[4-(methylsulfinyl)phenyl]pyrazole (FR143166) in the tail-pinch test in mice. The p.o. and i.t. injection of FR143166 exerted dose-dependent antinociceptive actions with ED(50) values of 24 mg/kg and 15 micro g/mouse, respectively. However, i.c.v. injection of FR143166 at a maximum dose of 128 micro g/mouse did not show any antinociceptive effect. The antinociceptive effect of FR143166 injected i.t. was abolished by co-administration of the nonselective serotonin (5-hydroxytryptamine, 5-HT) receptor antagonist, methysergide, but not by the adrenoceptor antagonists, phentolamine and propranolol. Moreover, the effect of FR143166 was also reversed by the 5-HT(2A) receptor antagonist, ketanserin, and the 5-HT(3) receptor antagonist, MDL-72222 (3-tropanyl-3,5-dichlorobenzoate). The effect of FR143166 was attenuated by p-chlorophenylalanine, but not by 6-hydroxydopamine plus nomifensine pretreatment. These results suggest that the descending serotonergic system, especially spinal 5-HT(2A) and 5-HT(3) receptors, is involved in the antinociceptive activity of spinally administered FR143166 on noxious mechanical stimuli.
D000700:Analgesics / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D008297:Male; D051379:Mice; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D011720:Pyrazoles / Q000737:chemistry / Q000494:pharmacology*; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism
C472514:1-(4-fluorophenyl)-3-methyl-5-(4-(methylsulfinyl)phenyl)pyrazole; D000700:Analgesics; D011720:Pyrazoles; D011985:Receptors, Serotonin; D012701:Serotonin