Acetylcholinesterase inhibitors therapy

People with dementia and their carers require access to a variety of health and social care services for treatment, information and counselling, community-based support, respite care and long-term residential care. Treatment may include behavioural therapies (e.g. reality orientation, cognitive stimulation and validation therapy) or pharmacological treatment with acetylcholinesterase inhibitors. 

Han, Y. R Tang, X. C. Prechnical and clinical progress with huperzine A a novel acetylcholinesterase inhibitor. In Becker, R. Giacobini, E., editors. Alzheimer Disease From Molecular Biology to Therapy. Boston, MA Birkhauser 1996, 245-250. 

Slip E, Sepehry AA, Chouinard S (2007) Add-on therapy with acetylcholinesterase inhibitors for memory dysfunction in schizophrenia a systematic quantitative review. Part 2. Clin Neuropharmacol 30 218-229. 

There are no effective therapies for Alzheimer s disease and no cure. Treatment aims to enhance cholinergic transmission. The most useful drugs are central acetylcholinesterase inhibitors, for example donepezil. Acetylcholinesterase is the enzyme that normally breaks down acetylcholine after it has interacted with its receptors at the synapse. Inhibition of this enzyme in the brain increases the amount of acetylcholine available and prolongs its action. These drugs produce a modest improvement in memory or slow progression of symptoms in some patients. The response to anti-cholinesterase drugs may take several weeks. Their use is limited by side effects, which can be severe. 

This drug is an acetylcholinesterase inhibitor used in the therapy of mild to moderate Alzheimer s dementia. 

Does therapy with acetylcholinesterase inhibitors affect the underlying dementia associated with Alzheimer s disease ... 

Munoz-Torrero D (2008) Acetylcholinesterase inhibitors as disease-modifying therapies for Alzheimer s disease. Curr Med Chem 15 2433-2455 Muntani G, Janue A, Fernandez N, Odena MA, Oliveira E, Boluda S, Portero-Otin M, Naudi A, Boada J, Pamplona R, Ferrer 1 (2010) Modification of brain lipids but not phenotype in alpha-synucleinopathy transgenic mice by long-term dietary n-3 fatty adds. Neurochem Int 12 Nov 2009 [Epub ahead of print]... 

Munoz-Torrero D (2008) Acetylcholinesterase inhibitors as disease-modifying therapies for Alzheimer s disease. CurrMed Chem 15 2433-2455... 

One of the clinical signs associated with MeHg intoxication is a myasthenia gravis-like muscle weakness in adults (Rustam et al. 1975), a syndrome which responded well to therapy with neostigmine, a reversible acetylcholinesterase inhibitor. In this syndrome, two effects of MeHg on synaptic transmission at the neuromuscular junction were demonstrated using intracellular microelectrode recording techniques (Atchison and Narahashi 1982 Atchison et al. 1984). First, nerve-evoked, synchronous quantal release of acetylcholine (ACh) is inhibited, as indicated by a decrease in end-plate potential (EPP) amplitude. Second, spontaneous quantal release... 

Neurotransmitters are removed by translocation into vesicles or destroyed in enzyme-catalysed reactions. Acetylcholine must be removed from the synaptic cleft to permit repolarization and relaxation. A high affinity acetylcholinesterase (AChE) (the true or specific AChE) catalyses the hydrolysis of acetylcholine to acetate and choline. A plasma AChE (pseudo-AChE or non-specific AChE) also hydrolyses acetylcholine. A variety of plant-derived substances inhibit AChE and there is considerable interest in AChE inhibitors as potential therapies for cognition enhancement and for Alzheimer s disease. Organophosphorous compounds alkylate an active site serine on AChE and the AChE inhibition by this mechanism is the basis for the use of such compounds as insecticides (and unfortunately also as chemical warfare agents). Other synthetics with insecticidal and medical applications carbamoylate and thus inactivate AChE (Table 6.4). 

Braginskaya F. 1., Molochkina E. M., Zorina O. M. et al. New synthetic bioantioxidants - acetylcholinesterase (AChE) inhibitors, in Alzheimer Disease From Molecular Biology to Therapy. R. Becker and E. Giacobini (eds.). Birkhauser-Boston. 1996, 337-342. 

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