Investigation into Anti-Alzheimer Activity of Newly Developed Phthalimide Derivatives in Experimental Animals

The present study was designed to investigate anti-Alzheimer's activity and to quantify brain neurotransmitter of newly developed isoindoline-1,3-dione derivatives (IDDs). The anti-Alzheimer's activity was evaluated using the elevated plus maze (EPM) and Morris water maze (MWZ) tests. Rats were divided into five groups, each containing six animals, which were treated with vehicle, scopolamine, donepezil and newly developed phthalimide derivatives (IDDs). Each model was studied for 5 days and the in-vivo anti-oxidant activity indices of brain including catalase, lipid peroxidase (LPO), glutathione (GSH) and acetylcholinesterase (AChE) levels were estimated spectrophotometrically. The levels of neurotransmitters serotonin and dopamine were estimated in rat brain homogenate using HPLC method. Treatment with high dose (30 mg/kg) of IDD showed significant anti-Alzheimer's activity in EPM and MWM tests in a dose-dependent manner in comparison with standard drug donepezil (4 mg/kg). In estimating the biochemical parameters, the level of catalase in the test group increased significantly, whereas LPO and GSH levels in treated groups decreased as compared to the untreated disease control group. The HPLC method confirmed that the concentrations of biogenic amines like dopamine and serotonin were significantly increased in phthalilmide group as compared to the control group. Thus, the present study reveals that the newly developed IDDs exhibit anti-Alzheimer's activity in various experimental animal models.