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

摘要

Albeit conflicting, evidence suggests that 5-HT(3) receptor partial agonists as well as alpha(2NON-A)-adrenoceptor agonists might be involved in antinociception. MD-354 (m-chlorophenylguanidine) can be viewed as the first example of a rather selective 5-HT(3)/alpha(2B)-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 (ED(50)=0.5 mg/kg), but a combination of an inactive dose 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 (ED(50)=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.