Acetylcholinesterase reversible inhibitor

An adjacent tnfluoromethyl group sharply increases the electrophilic character of the carbonyl carbon Compounds that readily form hydrates and hemiacetals show a time-dependent reversible mhibition of the en yme acetylcholinesterase (equation 2), in which the tight complex makes inhibition only partially reversible [75] In comparison with a nonfluormated analogue, several aliphatic ketones flanked by CFj and CF2 groups, are exceptionally potent reversible inhibitors of acetylcholinesterase, as documented by companson of inhibition constants shown in equation 3 [16 ... 

Galantamine is a reversible inhibitor of acetylcholinesterase that also possesses nicotinic receptor agonist properties, and which is used in mild-to-moderate dementia in Alzheimer s disease. 

Pharmacology Galantamine is a competitive and reversible inhibitor of acetylcholinesterase. While the precise mechanism of galantamine s action is unknown, it may exert its therapeutic effect by enhancing cholinergic function. Pharmacokinetics ... 

Donepezil is a selective, reversible inhibitor of acetylcholinesterase. Its long half-hfe allows for once-daUy dosing. Several stud-... 

The reversible inhibitors, which have a short to moderate duration of action, fall into two categories. Type one, exemplified by edrophonium, forms an ionic bond at the anionic site and a weak hydrogen bond at the esteratic site of acetylcholinesterase. Type two, exemplified by neostigmine, forms an ionic bond at the anionic site and a hydrolyzable covalent bond at the esteratic site. The irreversible inhibitors, exemplified by organophosphorus compounds (diisopropyl fluorophosphate, parathion,... 

Donepezil is primarily a reversible inhibitor of acetylcholinesterase with a long elimination half-life. It lacks the hepatotoxicity of tacrine but frequently causes nausea, vomiting and diarrhoea. These side effects, together with occasional bradycardia, sycope and changes in the sleep architecture, are directly associated with a central and peripheral enhancement of cholinergic function. At the present time, donepezil is the most widely prescribed anticholinesterase in the United States and Europe. 

Q5 Donepezil is a reversible inhibitor of acetylcholinesterase, which is administered once daily. The starting dosage is 5 mg daily at bedtime, increasing if necessary after one month to 10 mg daily. 

Oxazocine 119 is a synthetic derivative of galanthamine 162. The latter is a tertiary alkaloid, isolated from amaryllidaceae, which is a central acting competitive and reversible inhibitor of acetylcholinesterase that enhances cognitive functions in Alzheimer s patients. However, oxazocine 119 showed a decreased potency as an acetylcholinesterase inhibitor and a marked selectivity with respect to butyrylcholinesterase, probably because butyrylcholinesterase accommodates steric bulk around the catalytic site, better than acetylcholinesterase <2003BML2389>. 

These compounds inhibit the hydrolysis of the neurotransmitter acetylcholine by the enzyme acetylcholinesterase within the mammalian nervous system (Zwiener and Ginsburg, 1988). This inhibition causes acetylcholine levels to rise, thus causing cholinergic hyperstimulation at muscarinic and nicotinic receptors. There are important differences in the way carbamates and OPs bind to acetylcholinesterase as well as their abililty to affect the CNS. Carbamates are reversible inhibitors of cholinesterase enzymes. Carbamates create a reversible bond to the cholinesterase enzyme through carbamylation which can spontaneously hydrolyze, reversing toxicity. Carbamate poisoning produces toxicity similar to that of OPs however, the toxicity is usually of a shorter duration and less severe in nature (Lifshitz et al, 1994). In contrast, OPs inhibit cholinesterase via an irreversible bond of phosphate radicals... 

Donepezil acts primarily as a reversible inhibitor of acetylcholinesterase with a half-life of over 70 hours. Prolonged paralysis lasting several hours and requiring postoperative mechanical ventilation in the intensive care unit has been reported after the use of suxamethonium in a patient taking long-term donepezil (285). 

Prevention of organophosphate toxicity is aimed at protecting the acetylcholine receptor and/or acetylcholinesterase itself. Atropine can be used to prevent as well as to treat organophosphate poisonings. In addition, use of reversible inhibitors of acetylcholinesterase has been used to prevent organophosphate... 

This compound showed an 18,000-fold preference for acetylcholinesterase over bu-tyrylcholinesterase. It was a reversible inhibitor in a concentration-dependent manner. 

The physiological activity of acetylcholine relies on local release, stimulation of the receptor, then rapid hydrolysis (deacetylation) by acetylcholinesterase, which results in deactivation. The indole alkaloid physostigmine, from the West African calabar bean, and the relatively simple synthetic compound pyridostigmine, which has a more obvious relationship to choline, are reversible inhibitors of acetylcholinesterase. Controlled inhibition of the enzyme by such drugs, which results in a build-up of ACh, is useful in conditions such as myasthenia gravis, a muscle weakness, which is caused by insufficient production of ACh. 

Radio, Z., and Taylor, P. (2001), Interaction kinetics of reversible inhibitors and substrates with acetylcholinesterase and its fa.scLculin 2 complex, J. Biol. Chem. 276, 4622-4633,... 

The absolute configuration of Sarin and of related acetylcholinesterase inhibitors has been elucidated , an approach that should be potentially useful in obtaining information about the topography of the esteratlc site. The claim has been made that optical rotatory dispersion measurements detected conformational changes in acetylcholinesterase in the presence of heat, alkali, acetylhomochollne, and a reversible inhibitor. 

Donepezil is a potent reversible inhibitor of acetylcholinesterase that... 

Huperzine A (49) is a sesquiterpene alkaloid isolated from a traditional Chinese herbal remedy, Huperzia serrata ( Qian Ceng Ta ) in 1986 [128], This compound has been proved to be a potent, selective and reversible acetylcholinesterase (AChE) inhibitor, and demonstrated memory enhancement and neuroprotective functions in clinical trials as a therapeutic against Alzheimer s disease (AD) in the People s Republic of China [129, 130], In 2004, a phase II clinical trial focused on its cognitive function was initiated by the National Institute on Aging (NIA) in the United States [131], ZT-1 (50), considered more selective than huperzine A, was developed as a semi-synthetic derivative of 49 by cooperation of the Shanghai Institute of Materia Medica and Debiopharm of Switzerland and is currently... 

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