A Novel Pregabalin Functionalized Salicylaldehyde Derivative Afforded Prospective Pain, Inflammation, and Pyrexia Alleviating Propensities

摘要

A novel pregabalin derivative named as pregsal ((S,E)-3-(((2-hydroxybenzylidene)amino)methyl)-5-methylhexanoic acid) was synthesized by a simple imination reaction between pregabalin and salicylaldehyde and was evaluated in the in vivo testing paradigms. The compound was characterized by UV, IR, H-1, C-13 NMR, HR ESI-MS, and elemental analysis. It was screened (30, 50, 75, and 100mg/kg) for antinociceptive, anti-inflammatory, and antipyretic activities in relation to pregabalin. The synthesized compound significantly attenuated the tonic acetic acid-induced nociceptive pain (30mg/kg (P<0.05), 50mg/kg (P<0.01), 75 and 100mg/kg (P<0.001)), and thermal-induced hyperalgesia (P<0.001). These activities were succinctly antagonized (P<0.05, P<0.01, P<0.001) by naloxone and pentylenetetrazole, implicating the involvement of opioidergic and GABAergic mechanisms. The compound also inhibited the temporal inflammatory response and alleviated the yeast-induced pyrexia (P<0.05, P<0.01, and P<0.001). These findings suggest that the synthesized compound possessed prospective pain, inflammation, and pyrexia relieving propensities and therefore may serve as a potential drug candidate for the therapeutic management of chronic pain conditions.