2ʹ,3,3,5ʹ-Tetramethyl-4ʹ-nitro-2ʹH-1,3ʹ-bipyrazole exerts antinociceptive effect using various nociception models

Background: 2ʹ,3,3,5ʹ-Tetramethyl-4ʹ-nitro-2ʹH-1,3ʹ-bipyrazole (TMNB) is a novel bipyrazole compound that exhibited antidiabetic and anti-inflammatory properties. However, its analgesic effect has not been investigated. This study aimed to assess the antinociceptive activity of TMNB using different nociception mouse models. Methods: TMNB doses (50, 100, 150, and 200 µg/kg) were assessed in mice using the acetic acid-induced writhing test, hot plate test, and formalin-induced paw licking assay. The effects were compared to those of mice treated with acetylsalicylic acid or morphine in the presence or absence of naloxone. Capsaicin- and glutamate-induced paw-licking tests were also used to evaluate the involvement of the vanilloid and glutamatergic systems, respectively. Results: TMNB produced significant dose-dependent inhibition of nociceptive behavior in the acetic acid-induced writhing test, showing 66% inhibition at a dose of 200 µg/kg. TMNB also caused a significant increase in the latency period in response to the hot plate test (68.2% at 200 µg/kg), and significantly inhibited both the neurogenic and inflammatory phases in the formalin-induced paw-licking test. Naloxone significantly reverses the effect of TMNB in both the hot plate test and formalin-induced paw-licking test. Moreover, TMNB significantly inhibited the neurogenic nociception induced by intraplantar injections of glutamate and capsaicin (53% and 77.1%, respectively at a dose of 200 µg/kg). Conclusion: TMNB possesses antinociceptive activity in mice that is mediated through both central and peripheral pathways.