A review on cholinesterase inhibitors for Alzheimer’s disease

Anand, Preet; Singh, Baldev

doi:10.1007/s12272-013-0036-3

Cited by 550 publications

(320 citation statements)

References 109 publications

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“…Cholinesterase inhibitors increase the cholinergic transmission specifically by preventing acetylcholinesterase (AChE) which hydrolyses acetylcholine. 1 Incredible significance has been given for the identification of neurotransmitter component concerned in the characteristic indication of neurological and psychiatric disorders. 2 Acetylcholinesterase has been ended up being the most conceivable remedial focus for the indicative management of Alzheimer's disease.…”

Section: Introductionmentioning

confidence: 99%

In vitro & ex vivo Acetylcholinesterase Inhibitory Activity of Morinda citrifolia Linn (Noni) Fruit Extract

Jeyabalan¹,

Subramanian²,

Cheekala³

et al. 2017

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Background: Psychological problem is a key medical issue for numerous neuropsychiatric and neurodegenerative diseases, for example, schizophrenia, Alzheimer's, dementia, seizure and Parkinsonism. Morinda citrifolia (Noni) has been utilized for a considerable length of time to cure or counteract assortment of diseases by conventional therapeutic professionals in Hawaii and Polynesia. Objective: The present study is focused to identify the neuroprotective activity of Morinda citrifolia fruit extract (MCFE) on in vitro and ex vivo animal model by inhibition of acetylcholinesterase (AChE), an enzyme target used for the treatment of Alzheimer's disease. Methods: Acetylcholinesterase inhibition assay was performed by in vitro & ex vivo methods as described by Ellman et al. In vitro antioxidant assay of the extract was performed by DPPH free radical scavenging activity & nitric oxide scavenging activity. Statistical analysis used: Statistical analysis was carried out using non linear regression analysis for plotting the line of best fit for the observed values using GraphPad Prism software. Results: By performing in vitro antioxidant assay the IC 50 value of the standard quercetin was found to be 46.22 µg/ml as compared to the MCFE which has an IC 50 value of 43.14 µg/ml for DPPH free radical scavenging activity. Similarly the IC 50 value of the standard ascorbic acid was found to be 81.85 µg/ml as compared to the MCFE which has an IC 50 value of 148.0 µg/ml for nitric oxide scavenging activity. Acetylcholinesterase inhibition assay was performed by in vitro method and the IC 50 value of MCFE and neostigmine was found to be 31.84 µg/ml & 19.71 µg/ml respectively. Conclusions: The present study investigated the neuroprotective activity of MCFE and it was identified by both in vitro and ex vivo techniques that the phytoconstituents has the ability to improve the learning and memory function by inhibiting the acetylcholinesterase. Key words:Morinda citrifolia, Noni, Acetylcholinesterase, Neuroprotective activity, in vitro, ex vivo. Key Messages: The present study investigated the neuroprotective activity of Morinda citrifolia and it was identified by both in vitro and ex vivo techniques that the phytoconstituents in the plant can improve the learning and memory function by inhibiting the acetylcholinesterase. Further the antioxidant potential of the plant was also evident from the DPPH and nitric oxide scavenging activity. Future studies may be designed for chronic administration of Morinda citrifolia to further investigate the effect on in vivo experimentation and also to identify the safety and efficacy parameters at both preclinical and clinical stages.

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Section: Introductionmentioning

confidence: 99%

In vitro & ex vivo Acetylcholinesterase Inhibitory Activity of Morinda citrifolia Linn (Noni) Fruit Extract

Jeyabalan¹,

Subramanian²,

Cheekala³

et al. 2017

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“…Agents as Rivastigmine, that contain a carbamyl group, are typical pseudo-irreversible AChEIs 14,15 that give carbamylation of active site serine residue and form a carbamoyl-enzyme intermediate that will be slowly hydrolyzed in order to give back the native enzyme.…”

Section: Introductionmentioning

confidence: 99%

NewN,N-dimethylcarbamate inhibitors of acetylcholinesterase: design synthesis and biological evaluation

Vita

Pandolfi

Ornano

et al. 2016

Journal of Enzyme Inhibition and Medicinal Chemistry

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A series of N,N-dimethylcarbamates containing a N,N-dibenzylamino moiety was synthesized and tested to evaluate their ability to inhibit Acetylcholinesterase (AChE). The most active compounds 4 and 8, showed 85 and 69% of inhibition at 50 mM, respectively. Furthermore, some basic SAR rules were outlined: an alkyl linker of six methylene units is the best spacer between the carbamoyl and dibenzylamino moieties; electron-withdrawal substituents on aromatics rings of the dibenzylamino group reduce the inhibitory power. Compound 4 produces a slow onset inhibition of AChE and this is not due to the carbamoylation of the enzyme, as demonstrated by the time-dependent inhibition assay of AChE with compound 4 and by MALDI-TOF MS analysis of trypsinized AChE inhibited by compound 4. Instead, compound 4 could act as a slow-binding inhibitor of AChE, probably because of its high conformational freedom due to the linear alkyl chain.

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“…1), we postulated that RS67333 could improve learning and memory by not only activating 5-HT 4 R but also, inhibiting acetylcholinesterase (AChE) activity. Indeed, several early studies reported that the inhibition of AChE improved cognition and that this effect is the main reason for the initial use of donepezil, galantamine, and rivastigmine as cognitive enhancers in AD (19,20). AChE inhibition has also been reported to improve performances in healthy rodents or animal models of memory deficiency (21).…”

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confidence: 99%

Design of donecopride, a dual serotonin subtype 4 receptor agonist/acetylcholinesterase inhibitor with potential interest for Alzheimer's disease treatment

Lecoutey

Hédou

Freret

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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RS67333 is a partial serotonin subtype 4 receptor (5-HT 4 R) agonist that has been widely studied for its procognitive effect. More recently, it has been shown that its ability to promote the nonamyloidogenic cleavage of the precursor of the neurotoxic amyloid-β peptide leads to the secretion of the neurotrophic protein sAPPα. This effect has generated great interest in RS67333 as a potential treatment for Alzheimer's disease (AD). We show herein that RS67333 is also a submicromolar acetylcholinesterase (AChE) inhibitor and therefore, could contribute, through this effect, to the restoration of the cholinergic neurotransmission that becomes altered in AD. We planned to pharmacomodulate RS67333 to enhance its AChE inhibitory activity to take advantage of this pleiotropic pharmacological profile in the design of a novel multitargetdirected ligand that is able to exert not only a symptomatic but also, a disease-modifying effect against AD. These efforts allowed us to select donecopride as a valuable dual (h)5-HT 4 R partial agonist (K i = 10.4 nM; 48.3% of control agonist response)/(h)AChEI (IC 50 = 16 nM) that further promotes sAPPα release (EC 50 = 11.3 nM). Donecopride, as a druggable lead, was assessed for its in vivo procognitive effects (0.1, 0.3, 1, and 3 mg/kg) with an improvement of memory performances observed at 0.3 and 1 mg/kg on the object recognition test. On the basis of these in vitro and in vivo activities, donecopride seems to be a promising drug candidate for AD treatment.

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A review on cholinesterase inhibitors for Alzheimer’s disease

Cited by 550 publications

References 109 publications

In vitro & ex vivo Acetylcholinesterase Inhibitory Activity of Morinda citrifolia Linn (Noni) Fruit Extract

In vitro & ex vivo Acetylcholinesterase Inhibitory Activity of Morinda citrifolia Linn (Noni) Fruit Extract

NewN,N-dimethylcarbamate inhibitors of acetylcholinesterase: design synthesis and biological evaluation

Design of donecopride, a dual serotonin subtype 4 receptor agonist/acetylcholinesterase inhibitor with potential interest for Alzheimer's disease treatment

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