The antinociceptive effect of FR140423 in mice: involvement of spinal alpha(2)-adrenoceptors.
We investigated the role of the spinal noradrenergic system in the antinociceptive effect of FR140423, 3-(difluoromethyl)-1-(4-methoxyphenyl)-5-[4-(methylsulfinyl)phenyl]py razole, by using the tail-pinch test in mice and various adrenoceptor antagonists. The antinociceptive effect of FR140423 injected i.t. was completely abolished by co-administration of the non-selective alpha-adrenoceptor antagonist phentolamine and the alpha(2)-adrenoceptor antagonist yohimbine but not by the alpha(1)-adrenoceptor antagonist prazosin or the beta-adrenoceptor antagonist propranolol. Oral administration of FR140423, at doses of 5-80 mg/kg, produced a dose-dependent antinociceptive effect with an ED(50) value of 19 mg/kg. This antinociception was abolished by i.t., but not i.c.v., injection of phentolamine and yohimbine (10 microg/mouse). These results suggest that alpha(2)-adrenoceptors in the spinal cord are involved in the antinociceptive effect of FR140423 against mechanical noxious stimulus as they are in the effect of morphine and clonidine.
Ochi
T
T
Department of Immunology and Inflammation, Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., 1-6, Kashima 2-chome, Osaka, 532-8514, Yodogawa-ku, Japan. takehiro_ochi@po.fujisawa.co.jp
Goto
T
T
D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects; D010147:Pain Measurement / Q000187:drug effects; D010646:Phentolamine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011720:Pyrazoles / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects* / Q000502:physiology; D013454:Sulfoxides; D015016:Yohimbine / Q000494:pharmacology
D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D000700:Analgesics; D000701:Analgesics, Opioid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D011720:Pyrazoles; D018341:Receptors, Adrenergic, alpha-2; D013454:Sulfoxides; C108904:3-(difluoromethyl)-1-(4-methoxyphenyl)-5-(4-(methylsulfinyl)phenyl)pyrazole; D015016:Yohimbine; D009020:Morphine; D011433:Propranolol; D011224:Prazosin; D010646:Phentolamine