ABSTRACT
A series of new 4-acyl-arylhydrazone pyrazole compunds were tested for antinociceptive activity using the inhibition of abdominal contortions induced by acetylcholine (4 mg/Kg, ip) in the mouse. Dipyrone was used for comparison of the antinociceptive potency of the compounds being tested. All drugs wee administered po in saline (dipyrone) or in propylene flycol 94-acyl-arylhydrazones). The maximum response induced by dipyrone (86% inhibition) was assigned an efficacy index of 1.0. Although none of the compounds had an efficacy index greater than 1.0, all three reached 1.0. The two most potent compounds, Wd1 and W1g, which also had an efficacy similar to that of dipyrone, contain a p-N(CH3)2 and m-OH,p-OCH3 group in the aromatic ring of the acyl-hydrazone, respectively. W1d presented the lowest antinociceptive ED50 in the series (1.41 mg/Kg) and was eleven times more potent than dypyrone (ED50 = 15.80 mg/Kg). Other substitutions at the para position had lower potency than W1d. The present results indicate that the introduction of a group at the para postion of the acyl-arylhydrazone ring increases the antinociceptive activity of these compounds to provide compounds of the same efficacy but greater potency than dipyrone to which these new compounds ara structurally related. Other assays of nociceptive activity are veing used to characterize the mechanism of action of the potential new drugs