The role of acetylcholinesterase inhibitors such as neostigmine and rivastigmine on chronic pain and cognitive function in aging: A review of recent clinical applications

Abstract

Chronic pain in patients with Alzheimer's disease or dementia is a complex issue in the medical field; these patients suffer from the common causes of chronic pain, especially in geriatric medicine. To ensure the correct type and level of given treatment, medical care should be taken to avoid the contribution of chronic pain and cognitive impairment in the elderly population. Acetylcholinesterase inhibitors (AChE-Is) have been proven as an efficient therapeutic resource for significant improvement in dementia of Alzheimer's disease and chronic pain due to the fact that cholinergic deficit is considered as an early finding in cognitive impairment and persisting pain. Some AChE-Is are investigated here in terms of treatment of dementia and chronic pain management. Neostigmine has been used as an adjunct analgesic in the postoperative period and in combination with other analgesic medications in an intrathecal approach. Rivastigmine has, over the past ten years, become the approved agent for the management of dementia of mild to moderate Alzheimer's disease and has gained approval for treating different types of non-Alzheimer's dementia. In this review, we will focus on the two types of AChE-Is (rivastigmine and neostigmine) in the development of their clinical use and their respective mechanisms of actions on improving cognitive function and managing chronic pain.

Comprehensive Review on Alzheimer’s Disease: Causes and Treatment

“…Several physiological processes in AD destroy Ach-producing cells which reduce cholinergic transmission through the brain. Acetylcholinesterase inhibitors (AChEIs), which are classified as reversible, irreversible, and pseudo-reversible, act by blocking cholinesterase enzymes (AChE and butyrylcholinesterase (BChE)) from breaking down ACh, which results in increasing ACh levels in the synaptic cleft [ 95 , 96 , 97 ]. On the other hand, overactivation of NMDAR leads to increasing levels of influxed Ca 2+ , which promotes cell death and synaptic dysfunction.…”

Acetylcholinesterase Inhibitors for Alzheimer’s disease: Past, Present, and Potential Future

“…Upon reaction, it leaves behind a carbamate moiety attached to the AChE which requires significant energy to hydrolyze and reactivate/regenerate the enzyme. 38 The regeneration hydrolysis takes ~10 hours and thus is often referred to as pseudoirreversible inhibition. 39 Of note, rivastigmine was initially researched as a semi-synthetic derivative of physostigmine which is another carbamates AChEi that was once believed to have potential in the treatment of AD.…”

Isolation and Characterization of Acetylcholinesterase Inhibitors from Piper longum and Binding Mode Predictions

“…New insights into the pathophysiology of AD indicate that a cholinergic dysfunction, occurring especially in basal forebrain neurons, is one of the important pathways towards AD [3]. This hypothesis is supported by evidence that central cholinergic drugs (such as donepezil, rivastigmine, and galantamine) have a positive impact on the symptoms of AD [4].…”