Antinociceptive Action of 4-(5'-Dimethylamino)-Naphthalenesulfonyl-2(3H)-Benzoxazolone (W3D) on Animal Models of Pain via Inhibitory Effects on NO and iNOS.

The new synthetic anti-inflammatory agent, 4-(5'-dimethylamino)-naphthalenesulfonyl-2(3H)-benzoxazolone (W3D), has demonstrated definite biological activity both in vitro and in vivo. In this study, we investigated the antinociceptive effects of W3D on various animal pain models. Our results showed that W3D, at doses of 12.5 and 25 mg/kg, significantly reduced acetic acidinduced mice writhing by 65.9% and inhibited the pain response in the second phase of formalin-induced pain from 167.75 ± 6.76 s to 97.25 ±9.63 s. Moreover, W3D prolonged the latent period on the tail-immersion test, which was stronger than the positive drug, aspirin (50 mg/kg). However, W3D did not show analgesic activity on the hot plate test, indicating no central pain response. Furthermore, the antinociceptive effects of W3D were not antagonized by naloxone, EGTA, CaCl₂, and reserpine. However, LArginine was able to reverse the antinociceptive effect, indicating that W3D's antinociceptive effect does not depend on opioid receptors, Ca²⁺ concentration, or monoamine content. Instead, it is closely associated with nitric oxide (NO) content. In addition, W3D was found to alleviate nocifensive behavior and improve brain histopathology by inhibiting NO, inducible nitric oxide synthase (iNOS), and calcitonin gene-related peptide in nitroglycerin-induced migraine mice, with more than 50% inhibition ratio at only 12.5 mg/kg orally. However, noradrenaline, dopamine, and 5-hydroxytryptamine levels were not significantly altered after treatment with W3D. In conclusion, the presented data suggest that W3D can be considered a new non-steroidal anti-inflammatory and antinociceptive agent for the treatment of peripheral pain and migraine mediated by NO and iNOS. [ABSTRACT FROM AUTHOR]