title: PASS assisted prediction and pharmacological evaluation of novel nicotinic analogs for nootropic activity in mice.
abstract: The aim of present study is to predict the probable nootropic activity of novel nicotine analogues with the help of computer program, PASS (prediction of activity spectra for substances) and evaluate the same. Two compounds from differently substituted pyridines were selected for synthesis and evaluation of nootropic activity based on their high probable activity (Pa) value predicted by PASS computer program. Evaluation of nootropic activity of compounds after acute and chronic treatment was done with transfer latency (TL) and step down latency (SDL) methods which showed significant nootropic activity. The effect on scopolamine induced amnesia was also observed along with their acetylcholine esterase inhibitory activity which also showed positive results which strengthened their efficacy as nootropic agents through involvement of cholinergic system. This nootropic effect was similar to the effect of nicotine and donepezil used as standard drugs. Muscle coordination and locomotor activity along with their addiction liability, safety and tolerability studies were also evaluated. These studies showed that these compounds are well tolerable and safe over a wide range of doses tested along with the absence of withdrawal effect which is present in nicotine due to its addiction liability. The study showed that these compounds are true nicotine analogs with desirable efficacy and safety profile for their use as effective nootropic agents.
authors.affiliation: Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, India.
authors.forename: Navneet
authors.initials: N
authors.lastname: Khurana
authors.forename: Mohan Pal Singh
authors.initials: MP
authors.lastname: Ishar
authors.forename: Asmita
authors.initials: A
authors.lastname: Gajbhiye
authors.forename: Rajesh Kumar
authors.initials: RK
authors.lastname: Goel
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D003071:Cognition / Q000187:drug effects; D019295:Computational Biology / Q000379:methods*; D004353:Drug Evaluation, Preclinical; D005260:Female; D008124:Locomotion / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D051379:Mice; D009132:Muscles / Q000187:drug effects / Q000502:physiology; D009538:Nicotine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology*; D018697:Nootropic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology*; D011930:Reaction Time / Q000187:drug effects; D011978:Receptors, Nicotinic / Q000378:metabolism; D012601:Scopolamine / Q000494:pharmacology
chemical_list: D018697:Nootropic Agents; D011978:Receptors, Nicotinic; D009538:Nicotine; D012601:Scopolamine; D000110:Acetylcholinesterase