Antinociceptive property of new 4-acyl-arylhydrazone pyrazole compounds.
A series of new 4-acyl-arylhydrazone pyrazole compounds 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 were administered po in saline (dipyrone) or in propylene glycol (4-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, W1d 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 dipyrone (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 position 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 are structurally related. Other assays of nociceptive activity are being used to characterize the mechanism of action of the potential new drugs.
Matheus
M E
ME
Departamento de Farmacologia Básica e Clínica, Universidade Federal do Rio de Janeiro, Brasil.
Oliveira
L F
LF
Freitas
A C
AC
Carvalho
A M
AM
Barreiro
E J
EJ
D000005:Abdomen; D000109:Acetylcholine / Q000037:antagonists & inhibitors*; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D004177:Dipyrone / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D011720:Pyrazoles / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D013997:Time Factors
D000700:Analgesics; D011720:Pyrazoles; D004177:Dipyrone; D000109:Acetylcholine