Acetylcholine esterase inhibitor

Pontine cholinergic agonists and acetylcholine esterase inhibitors... 

The mode of action of the isobutylamides is unknown, although Miyakado et al. found that several isobutylamides (i.e. pipercide and related compounds) caused repetitive discharge when the nerve cord of the cockroach, Periplaneta americana was stimulated. We found that fagaramide was inactive as an acetylcholine esterase inhibitor in an m vitro assay(unpublished dat a). 

An extremely interesting area for bioassays is the group of acetylcholine-esterase inhibitors, the organophosphate and carbamate pesticides. First of all this is based on the need for rapid screening tests, allowing on-site testing of fruits and vegetables. Secondly there is the awareness that the cumulative effects... 

J. Haginaka, C. Seyama, Determination of enantiomers of l-benzyl-4-[(5,6-dimethoxy-l-indanon)-2-yl]methylpiperidine hydrochloride (E2020), a centrally acting acetylcholine esterase inhibitor, in plasma by liquid chromatography with fluorometric detection, J. Chromatogr. 577 (1992) 95-102. 

Development of sexual behavior can be affected by neonatal pharmacological treatment with the monoamine oxidase inhibitor pargyline, the monoamine depletor reserpine as well as with the acetylcholine esterase inhibitor pyridostigmine. These results suggest that biogenic amines are involved in sexual differentiation of the brain (refs. 162, 163). Pargyline treatment from day 1 to 14 or day 15 to 28 resulted in earlier development of puberty in female rats and delayed appearance of puberty in male rats. Male sexual behavior was decreased in both sexes. Treatment with reserpine on days 1, 4, 7 and 10 delayed the manifestation of puberty in both sexes, and caused disturbed female ovarian cycles and decreased male mounting behavior. 

The greatly increased nucleophilicity of the catalytic serine distinguishes it from all other serine residues and makes it an ideal candidate for modification via activity-based probes [58]. Of the electrophilic probe types to profile serine hydrolases, the fluorophosphonate (FP)-based probes are the most extensively used and were first introduced by Cravatt and coworkers [38, 39]. FPs have been well-known inhibitors of serine hydrolases for over 80 years and were first applied as chemical weapons as potent acetylcholine esterase inhibitors. As FPs do not resemble a peptide or ester substrate, they are nonselective towards a particular serine hydrolase, thus allowing the entire family to be profiled. FPs also show minimal cross-reactivity with other classes of hydrolases such as cysteine-, metallo-, and aspartylhydrolases [59]. Furthermore, FP-based probes react only with the active serine hydrolase, and not the inactive zymogen, allowing these probes to interact only with functional species within the proteome [59]. Extensive use of this probe family has demonstrated their remarkable selectivity for serine hydrolases and resulted in the identification of over 100 distinct serine hydrolases... 

An alternative therapeutic strategy has focused on improving cognitive features of HD, and the effect of this treatment on gene expression has been studied [76], R6/2 mice were treated from 5 weeks old, when they exhibit spatial learning difficulties, with a cocktail of tacrine (an acetylcholine esterase inhibitor, which results in a global increase of brain acetylcholine levels), moclobemide (an antidepressant that inhibits monoamine oxidase A and... 

As will become clear, this chapter is focused on toxicants for which the receptor is a high-affinity recognition site of the type discussed in the previous paragraphs. It should be noted explicitly that other toxicants have receptors, but fall into more complex situations not appropriate for this chapter. For example, some toxicants inhibit enzymes, or are themselves enzymes. Such interesting compounds include the organophosphate and carbamate insecticides (acetylcholine esterase inhibitors) and diphtheria toxin (an enzyme). 

Subsequently, Overman and co-workers reported an application of their method in an en-antioselective total synthesis of the alkaloid (-)-physostigmine (50), which as an effective acetylcholine esterase inhibitor is of interest for... 

Zayats, M., Kharitonov, A.B., Pogorelova, S.P., Lioubashevski, O., Katz, E., Willner, I. (2003). Probing photoelectrochemical processes in Au-CdS nanoparticle arrays by surface Plasmon resonance application for the detection of acetylcholine esterase inhibitors. J. Am. Chem. Soc. 125 16006-14. 

Rivastigmine tartrate (exelon) (2000) (40)Galantamine liydrobromide (reminyl) (2001) Figure 13.10. Approved acetylcholine esterase inhibitors. 

Some quaternary acetylcholine esterase inhibitors were analyzed by the Ruyter et al. 7 on an octyl column using heptanesulfonic acid containing mobile phase (Fig.15.5). Best column performance was observed at lower pH. Addition of tetramethylammonium to the mobile phase reduced tailing on some of the tested reversed-phase column materials. Tetramethylammonium could also be used to regulate the retention of the compounds analyzed. The quaternary compounds were isolated from biological material by means of ion-pair extraction. 

Ben2yl-4-piperidyl)methyl]-5,6-dimethoxy-1-indanone. Donepezil 1H-lnden-1-one, 2,3-dihydro-5,6-dimethoxy-2-((1-(phenylmethyl)-4-piperidinyl)methyl)-. Nootropic, A reversible acetylcholine esterase inhibitor used to treat Alzheimer s disease. Pfizer Inc. 

Aricept BNAG Donepezil hydrochloride E-2020, Nootropic, A reversible acetylcholine esterase inhibitor used to treat Alzheimer s... 

Behra, M., Eiard. C.. Cousin, X., and SirahLe, U- (2004) The use of zcbrallsh mutant.s to identify secondary target effects of acetylcholine esterase inhibitors. Taxicol. Sci. 77, 325-3.33. 

This class of xenobiotics is structurally and physiologically heterogeneous Carbaryl and Carbofuran are acetylcholin esterase inhibitors, whereas Chlorpropham (CIPC) is a herbicide, interfering with cell division [197]. The structure of carbamates is very different, as the amine can be aromatic, like in CIPC, or aliphatic, like in Carbaryl and Carbofuran. Everywhere, these microorganisms are able to hydrolyze the carbamate linkage by producing CO, alcohol, and the correqsonding amine, aromatic or aliphatic. 

The acetylcholine esterase inhibitor physostigmine has been labeled from [ C]methyl isocyanate (O Fig. 41.45). 

Other example of useful acetylcholine esterase inhibitors are N-methylpiperidine-4-yl acetate (lyo et al. 1997) and propionate (Kilbourn et al. 1998). 

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