Antinociceptive effect of novel pyrazolines in mice

Abstract

The antinociceptive effect of six novel synthetic pyrazolines (3-ethoxymethyl-5-ethoxycarbonyl-1H-pyrazole (Pz 1) and its corresponding 1-substituted methyl (Pz 2) and phenyl (Pz 3) analogues, and 3-(1-ethoxyethyl)-5-ethoxycarbonyl-1H-pyrazole (Pz 4) and its corresponding 1-substituted methyl (Pz 5) and phenyl (Pz 6) analogues) was evaluated by the tail immersion test in adult male albino mice. The animals (N = 11-12 in each group) received vehicle (5% Tween 80, 10 ml/kg, sc) or 1.5 mmol/kg of each of the pyrazolines (Pz 1-Pz 6), sc. Fifteen, thirty and sixty minutes after drug administration, the mice were subjected to the tail immersion test. Thirty minutes after drug administration Pz 2 and Pz 3 increased tail withdrawal latency (vehicle = 3.4 ± 0.2; Pz 2 = 5.2 ± 0.4; Pz 3 = 5.9 ± 0.4 s; mean ± SEM), whereas the other pyrazolines did not present antinociceptive activity. Doseeffect curves (0.15 to 1.5 mmol/kg) were constructed for the bioactive pyrazolines. Pz 2 (1.5 mmol/kg, sc) impaired motor coordination in the rotarod and increased immobility in the open-field test. Pz 3 did not alter rotarod performance and spontaneous locomotion, but increased immobility in the open field at the dose of 1.5 mmol/kg. The involvement of opioid mechanisms in the pyrazoline-induced antinociception was investigated by pretreating the animals with naloxone (2.75 µmol/kg, sc). Naloxone prevented Pz 3-but not Pz 2-induced antinociception. Moreover, naloxone pretreatment did not alter Pz 3-induced immobility. We conclude that Pz 3-induced antinociception involves opioid mechanisms but this is not the case for Pz 2.

Synthesis of Some Novel Azo Derivatives of 3,5‐Dimethly‐1‐(2‐hydroxyethyl)pyrazole as Potent Analgesic Agents

“…Moreover, the pyrazole nucleus ranks among those molecular structures related to potent analgesic activity [9][10]. In addition, thiadiazole or triazole derivatives were documented to be effective as anti-inflammatory agents [11][12][13].…”

Synthesis and analgesic effects of 2-(2-carboxyphenylsulfanyl)-N-(4-substitutedphenyl)acetamide derivatives

“…Mice that were able to remain on the rod longer than 180 s were selected for the test. Latency to fall from the rotating mill was recorded (Adzu et al, 2002;Tabarelli et al, 2004).…”

A pyrazolyl-thiazole derivative causes antinociception in mice

“…Indeed, pyrazole-derived compounds lacking such carbonyl groups have little or no anti-inflammatory activity, but some of them present a significant antinociceptive action (4,5,12,13). Accumulated evidence in the literature and in studies by our group suggests that the presence of a phenyl group at the 1 position of the pyrazole ring increases antinociceptive activity (7). In the present study, we show that a pyrazoline derivative with a phenyl-methylthiazole at the 1 position of the pyrazole ring may have significant antinociceptive activity, which is abolished by the removal of the methyl group in the thiazole ring.…”

“…In order to investigate the involvement of the opioid system in the antinociceptive effects of B50, animals were pretreated with naloxone (2.75 µmol/kg, sc) 20 min before the administration of B50 (80 µmol/kg, sc), morphine (6.5 µmol/kg, sc) or vehicle (10 mL/kg, sc). The doses of naloxone and morphine were selected according to Tabarelli et al (7).…”