MD-354 potentiates the antinociceptive effect of clonidine in the mouse tail-flick but not hot-plate assay

European Journal of Pharmacology
Anna WesolowskaMałgorzata Dukat

Abstract

Albeit conflicting, evidence suggests that 5-HT3 receptor partial agonists as well as alpha2NON-A-adrenoceptor agonists might be involved in antinociception. MD-354 (m-chlorophenylguanidine) can be viewed as the first example of a rather selective 5-HT3/alpha2B-adrenergic ligand. In a tail-flick test in mice, subcutaneous administration of MD-354 doses up to 30 mg/kg did not produce antinociception and failed to antagonize the effect of clonidine (ED50=0.5 mg/kg), but a combination of an inactive de of clonidine (0.25 mg/kg) that produced only 13% maximal possible effect (MPE) with an inactive dose of MD-354 (10 mg/kg, MPE=8%) produced an antinociceptive effect (MPE=83%). In the hot-plate assay, neither subcutaneous administration of MD-354 (3 to 30 mg/kg) alone nor in combination with clonidine (ED50=0.8 mg/kg) produced an antinociceptive effect. MD-354 was demonstrated to potentiate the antinociceptive effect of clonidine in the tail-flick assay, but its underlying mechanism remains to be determined.

References

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Citations

Apr 1, 2010·Basic & Clinical Pharmacology & Toxicology·Shawquia YoungMałgorzata Dukat
Dec 3, 2005·European Journal of Pharmacology·Magorzata Dukat, Anna Wesołowska
Nov 15, 2008·Journal of Neuroscience Methods·Natalie Ann Rasmussen, Lynne A Farr
Apr 28, 2007·CNS Drug Reviews·Malgorzata DukatShawquia Young

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