In vivo pharmacological profile of substituted (3-pyridyl)-2-phenylisoxazolidine analogues of nicotine as novel antinociceptives

Abstract

Nicotinic ligands have been studied as novel therapeutic interventions in pain therapeutics since a long time. Several nicotinic agonists have been withdrawn from later stages of clinical trials due to lack of efficacy or narrow therapeutic window. These have been documented to act in the central nervous system and produce a wide range of pharmacological effects, including memory enhancing and analgesic actions, antianxiety, antidepressant and muscle coordination. Taking cognizance of the wide pharmacological profile of nicotine and its ligands, it was decided to evaluate some novel isoxazolidine analogues of nicotine for their potential as analgesics, using animal models like Eddy’s hot plate and Tail immersion method. The compounds showed marked decrease in hyperalgesic response as compared to pentazocine at a wide range of doses. They were well tolerated as none of the compounds was found to have any seizure potential or mortality even at the highest doses. Thus, these compounds can be developed as potent antinociceptives with better safety profile than nicotine and other currently available pain therapeutics.