Opioidergic System-Mediated Antinociceptive Activity of Tofisopam

Abstract

Objective: In this study, it was aimed to investigate the antinociceptive activity potential of Tofisopam and to elucidate the possible involvement of opioid system in this effect.Material and Method: The antinociceptive efficacy potential of Tofisopam (25 and 50 mg/kg) was evaluated by hot-plate and acetic acid-induced writhing tests; while possible effects of this drug on the motor coordination of mice were evaluated with the Rota-rod tests.Result and Discussion: Tofisopam at a dose of 50 mg/kg significantly prolonged the reaction times of mice in hot-plate tests and reduced the number of writhing behaviors in writhing tests. These findings indicated that Tofisopam has antinociceptive activity mediated by central and peripheral mechanisms. Tofisopam did not change the motor activities of mice. Pre-administration of naloxone to investigate the possible involvement of opioid receptors in the antinociceptive effect abolished the antinociceptive activity of Tofisopam. To elucidate the opioid receptor subtypes mediating the effect, mechanistic studies were carried out with naloxonazine (μ-opioid receptor blocker), naltrindole (δ-opioid receptor blocker) and nor-binaltorphimine (ҡ-opioid receptor blocker). All agents antagonized the antinociceptive effect of Tofisopam. Obtained findings revealed that Tofisopam at a dose of 50 mg/kg have antinociceptive activity mediated by μ-, δ- and ҡ-oipiod receptors.