Parkinson's disease (PD) is the second most common neurodegenerative disorder, and there are no drugs that will directly tackle the inflammatory component of PD. In the present study, we assessed the novel glitazone for reversal of rotenone-induced toxicity in experimental mouse model. The 14 virtual glitazone compounds were subjected to molecular docking study for target protein 3CS8; among these, compound C25 and C34 have shown better binding activity. Pharmacokinetics studies were conducted for the above compounds in rat model to chose best one for further toxicity and efficacy studies. The compound C25 showed better kinetic profile when compared to C34 and better t 1/2 when compared to the standard pioglitazone. Compound C25 then tested for acute toxicity by OECD guideline 423 and evaluated for its neuroprotective activity in mouse model. The activity of the compound was assessed by the behavioral parameters on weekly intervals during the study period and estimated the antioxidant level in the brain homogenate. The compound has shown good activity dose-dependently; however, further research is required to confirm its activity and to support our hypothesis.
Background/Objectives Memory impairment (MI) and epilepsy go hand in hand, mainly in conditions of temporal lobe epilepsy (TLE). This disease comorbidity has been reported to worsen upon treatment. Hence this study aims to evaluate the extent of aggravating effect of phenytoin (PHT) at normal and reduced doses on MI associated with TLE and additionally assesses the protective effect of levetiracetam (LEV) on these adverse effects.
Methods Swiss albino mice of either sex (n = 36) were used for this study in which seizures were induced by intraperitoneal administration of pilocarpine (300 mg/kg i.p.) followed by evaluation of antiepileptic activity by technique of Racine's scale for convulsive scores. Errors (a factor denoting MI) were assessed using radial arm maze. Finally brain biochemical measures of acetylcholinesterase and glutamate along with cresyl violet staining and estimation of total neuronal number of the hippocampus were performed.
Results Exacerbation of MI by PHT was observed, where the extent of MI was found to be lesser in the reduced dose approach (PHTR: 28.50 ± 1.03; p ≤ 0.05). However, this tactic in dose reduction was interfered with the antiepileptic potential of the drug. Attenuation of MI upon combining with LEV, without an interference in the principal treatment, was observed equally in the behavioral and brain aspects of the study (PHTN + LEV: 1.33 ± 0.33 and PHTR + LEV: 1.00 ± 0.17; p ≤ 0.05).
Conclusions The promising effects of LEV could thus aid in proposing a new management remedy for TLE to minimize the adverse effect associated with it.
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