The antinociceptive effect of FR140423 in mice: involvement of spinal alpha(2)-adrenoceptors |
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Authors: | Ochi T Goto T |
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Institution: | 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 |
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Abstract: | 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. |
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