Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by a gradual decline in memory associated with shrinkage of brain tissue, with localized loss of neurons mainly in the hippocampus and basal forebrain, with diminished level of central cholinergic neurotransmitter-acetylcholine and also reported to be associated with accumulation of ubiquitinated proteins in neuronal inclusions and also with signs of inflammation. In these disorders, the abnormal protein aggregates may themselves trigger the expression of inflammatory mediators, such as cyclooxygenase 2 (COX-2). In the present study, the effects of Meloxicam, Selegiline, and coadministration of these drugs on scopolamine-induced learning and memory impairments in mice were investigated. Rectangular maze test, Morris water maze test, Locomotor activity, and Pole climbing test were conducted to evaluate the learning and memory parameters. Various biochemical parameters such as acetylcholinesterase(AChE), TBARS assay, catalase activity, and DPPH assay were also assessed. The present study demonstrates that Meloxicam, Selegiline, and co-administration of these test drugs had potential therapeutic effects on improving the antiamnesic activity in mice through inhibiting lipid peroxidation, augmenting endogenous antioxidant enzymes, and decreasing acetylcholinesterase activity in brain. The memory enhancing capacity of the drugs was very significant when compared to disease control (P < 0.001).

Highlights

  • Alzheimer’s disease (AD) is a progressive neurodegenerative brain disorder that is slow in onset but leads to dementia, unusual behavior, personality changes, and death [1]

  • A decrease in acetyl choline in the brain of patients with AD appears to be a critical element in producing dementia [3]

  • The results showed that synergistic action of meloxicam and selegiline was significant (P < 0.05) and is comparable to the standard drug

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Summary

Introduction

Alzheimer’s disease (AD) is a progressive neurodegenerative brain disorder that is slow in onset but leads to dementia, unusual behavior, personality changes, and death [1]. A decrease in acetyl choline in the brain of patients with AD appears to be a critical element in producing dementia [3]. AChE inhibitors from general chemical classes such as physostigmine, tacrine, galantamine, and heptylphysostigmine have been tested for the symptomatic treatment of AD [4]. Nonselectivity of these drugs, their limited efficacy, poor bioavailability, adverse cholinergic side effects in the periphery, narrow therapeutic ranges, and hepatotoxicity are among the several limitations to their therapeutic success [5]. It is worthwhile to explore the utility of other existing medicines for the treatment of various cognitive disorders [6]

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