Acetylcholinesterase (AChE) remains a highly viable target for the symptomatic improvement in Alzheimer's disease (AD) because cholinergic deficit is a consistent and early finding in AD. The treatment approach of inhibiting peripheral AchE for myasthenia gravis had effectively proven that AchE inhibition was a reachable therapeutic target. Subsequently tacrine, donepezil, rivastigmine, and gal...

The complex nature of Alzheimer's disease calls for multidirectional treatment. Consequently, the search for multi-target-directed ligands may lead to potential drug candidates. The aim of the present study is to seek multifunctional compounds with expected activity against disease-modifying and symptomatic targets. A series of 15 drug-like various substituted derivatives of 2-(benzylamino-2-hy...

Acetylcholinesterase (AChE) inhibitors are widely used for the symptomatic treatment of Alzheimer's disease and other dementias. More recent use is for myasthenia gravis. Many of these inhibitors interact with the second known cholinesterase, butyrylcholinesterase (BChE). Further, evidence shows that acetylcholine plays a role in suppression of cytokine release through a "cholinergic anti-infla...

Cognitive impairment, complex movement disorders, and high risk of falls are all interrelated , levodopa-unresponsive symptoms in patients with advanced Parkinson's disease. Although Parkinson's disease is conventionally viewed as a motor syndrome that results from nigrostriatal dopaminergic denervation, there is also an intricate interplay between multisystem degeneration and neurotransmitter ...

Alzheimer's disease (AD) is a neurodegenerative disorder, and is the commonest cause of dementia. Acetylcholinesterase inhibitors (AChEIs) were developed under the cholinergic hypothesis of AD. Therapeutic strategies with these drugs aimed to enhance cholinergic neurotransmission in specific parts of the brain, and to improve the clinical symptoms of AD. Donepezil, galantamine and rivastigmine ...

The cholinergic hypothesis of Alzheimer's disease (AD) has provided the rationale for the current pharmaco-therapy of this disease, in an attempt to reduce the cognitive decline caused by cholinergic deficits. Nevertheless, the search for potent and long-acting acetylcholinesterase (AChE) inhibitors that exert minimal side effects in AD patients is still ongoing. AChE inhibitors are currently t...

Abstract The condensation of tacrine aminopolymethylene derivatives with diethyl (ethoxymethylidene)malonate led to the new hybrid compounds—conjugates, which were effective inhibitors acetylcholinesterase (AChE) (IC 50 up 0.538 μM) and butyrylcholinesterase 0.0314 μM). They can displace propidium iodide from peripherical anionic site AChE at level reference drug donepezil demonstrate a weak an...

Donepezil, a highly selective acetylcholinesterase inhibitor (AChEI), is approved as a symptomatic treatment mild, moderate, and severe Alzheimer's disease (AD). Donepezil exerts its treatment effect through multiple mechanisms of action including nicotinic receptor stimulation, mitigation of excitotoxicity, and influencing APP processing. The use of donepezil at higher doses is justified given...

The structure of Torpedo californica acetylcholinesterase is examined in complex with several inhibitors that are either in use or under development for treating Alzheimer's disease. The noncovalent inhibitors vary greatly in their structures and bind to different sites of the enzyme, offering many different starting points for future drug design.

Neurotoxic organophosphorous compounds are known to modulate their biological effects through the inhibition of a number of esterases including acetylcholinesterase (AChE), the enzyme responsible for the degradation of the neurotransmitter acetylcholine. In this light, molecular modeling studies were performed on a collection of organophosphorous acetylcholinesterase inhibitors by the combined ...