Chapter 53: Brain selective inhibition of acetylcholinesterase: a novel approach to therapy for Alzheimer's disease

Enz, Albert; Amstutz, René; Boddeke, Hendrikus; Gmelin, G.; Malanowski, Jan

doi:10.1016/s0079-6123(08)62429-2

Cited by 290 publications

(157 citation statements)

References 12 publications

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“…Rivastigmine does not appear to be significantly associated with any of these AEs, and this may be due to its preferential affinity for the G1 rather than the G4 molecular form of AChE. 22,51 As previously discussed, G4 AChE is the predominant form in the periphery and particularly at the presynaptic membrane of the skeletal neuromuscular junction, which may explain why rivastigmine appears to be associated with a lower incidence of muscle cramps or weakness than, for example, donepezil. 6,22,52,53 Sleep disturbances and changes in sleep-wake cycles are common clinical features of dementia.…”

Section: Central and Peripheral Nervous System Adverse Eventsmentioning

confidence: 93%

“…Rivastigmine increases REM density, indicating activity in the hippocampus without any corresponding change in REM latency, suggesting minimal disturbance of brain stem function. 51,60 Further evidence of the brain region selectivity of rivastigmine comes from the improvement in or lack of sleep AEs in patients with AD, Lewy body dementia (LBD), and Parkinson's disease dementia (PDD) receiving this agent. [61][62][63][64][65] EPSs include muscle stiffness, slowness of movement, postural instability, body restlessness, gait imbalance, and tremor.…”

Section: Central and Peripheral Nervous System Adverse Eventsmentioning

confidence: 99%

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Cholinesterase Inhibitors for the Treatment of Alzheimer's Disease:

Grossberg

2003

Current Therapeutic Research

282

156

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Background: Cholinesterase (ChE) inhibitors currently used in the treatment of Alzheimer's disease (AD) are the acetylcholinesterase (AChE)-selective inhibitors, donepezil and galantamine, and the dual AChE and butyrylcholinesterase (BuChE) inhibitor, rivastigmine. In addition to differences in selectivity for AChE and BuChE, ChE inhibitors also differ in pharmacokinetic and pharmacodynamic properties, and these differences could significantly impact on safety, tolerability, and efficacy.Objective: The aim of this article was to provide an overview of the ChE inhibitors widely used in AD, focusing on key pharmacologic differences among agents and how these may translate into important differences in safety, tolerability, and efficacy in clinical practice.Methods: Using published literature collected over time by the author, a review was conducted, focusing on the pharmacology and clinical data of donepezil, galantamine, and rivastigmine.

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Section: Central and Peripheral Nervous System Adverse Eventsmentioning

confidence: 93%

Section: Central and Peripheral Nervous System Adverse Eventsmentioning

confidence: 99%

Cholinesterase Inhibitors for the Treatment of Alzheimer's Disease:

Grossberg

2003

Current Therapeutic Research

282

156

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“…EGb761 also inhibits acetylcholinesterase (AChE), the metabolizing enzyme of acetylcholine (Das et al, 2002). The inhibition of AChE is presently the most accepted and recognized therapeutic marker in the development of cognitive enhancers (Enz et al, 1993;Siddiqui and Levey, 1999;Das et al, 2002). Administration of EGb761 may help animals recruit cognitive resources when presented with ambiguous, discrepant, or potentially threatening stimuli.…”

Section: Discussionmentioning

confidence: 99%

Extract of Ginkgo biloba EGb761 Facilitates Extinction of Conditioned Fear Measured by Fear-Potentiated Startle

Yang

et al. 2006

Neuropsychopharmacol

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A standard extract of Ginkgo biloba (EGb761) has been used in the treatment of various common geriatric complaints including vertigo, short-term memory loss, hearing loss, lack of attention, or vigilance. We demonstrated that acute systemic administration of EGb761 facilitated the acquisition of conditioned fear. Many studies suggest the neural mechanism underlies extinction is similar to the acquisition. This raises a possibility that EGb761 may modulate and accelerate the fear extinction process. We tested this possibility by using fearpotentiated startle (FPS) on laboratory rats. Acute systemic injection of EGb761 (10, 20, or 50 mg/kg) 30 min before extinction training facilitated extinction in a dose-dependent manner. Intra-amygdaloid infusion of EGb761 (28 ng/side, bilaterally) 10 min before extinction training also facilitated extinction. Control experiments showed that facilitation effect of EGb761 was not the result of impaired expression of conditioned fear or accelerated forgetting. Rats previously injected with EGb761 showed significant FPS after retraining. Extinction of conditioned fear appeared to result from acute drug effects rather than from toxic action. Systemic administration of EGb761 immediately after extinction training did not facilitate extinction, suggested the EGb761 facilitation effect is contributed to the acquisition phase of extinction learning. Western blot results showed that extinction induced amygdaloid extracellular signal-regulated kinase (ERK1/2) phosphorylation was significantly elevated by EGb761 treatment. Intra-amygdala injection of ERK1/2 inhibitor PD98059 completely blocked the EGb761 effect. Therefore, acute EGb761 administration modulated extinction of conditioned fear by activating ERK1/2.

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“…Therefore, increasing central cholinergic activity by inhibiting cholinesterase enzymes is currently the main way of preventing neurodegenerative disorders. 20,21 One of the most widely used anti-cholinesterase drug galantamine is derived from plant sources. 22 Nicotinic and muscarinic receptor-modulating properties of galantamine contribute to the antipsychotic effect and development of cognitive dysfunction.…”

Section: Butyrylcholinesterase (Bche) Inhibitory Activitymentioning

confidence: 99%

Phytochemical Screening and Acetylcholinesterase and Butyrylcholinesterase Inhibitory and Thrombolytic Activities of Grewia abutilifolia Vent. & Juss. Leaf

Rafe¹,

Salam

Hossain³

et al. 2018

Dhaka Univ. J. Pharm. Sci

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Cholinesterase inhibitors offer the possible pathway to fight against various types of neurodegenerative diseases. Grewia abutilifolia is used extensively in traditional and folk medicines mainly to improve intellectual capabilities and memory enhancement purposes which support its possible effects against neurodegenerative disorders. We performed preliminary phytochemical screening to observe the presence of potential phytoconstituents of G. abutilifolia leaf extracts and evaluated acetylcholinesterase and butyrylcholinesterase inhibitory properties to measure its anti-cholinesterase activities. Preliminary phytochemical screening confirmed the presence of saponins, tannins, flavonoids, terpenoids, steroids, carbohydrates, coumarins, alkaloids etc. The petroleum ether (PESF), chloroform (CSF) and aqueous soluble fractions (AQSF) of the crude extract of the plant leaf were screened for bioactivities. The highest inhibition of acetylcholinesterase was exhibited by aqueous soluble fraction (AQSF) with IC50 = 5.73 ± 0.59 μg/ml, while the highest inhibition of butyrylcholinesterase was shown by petroleum ether soluble fraction (PESF) with IC50 = 6.57 ± 1.81 μg/ml in a dose-dependent manner. During assay for thrombolytic activity, the chloroform soluble fraction (CSF) revealed highest activity with 25.75 ± 1.62% clot lysis. These results of the present study suggested the effectiveness of G. abutilifolia against various neurological diseases.

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Chapter 53: Brain selective inhibition of acetylcholinesterase: a novel approach to therapy for Alzheimer's disease

Cited by 290 publications

References 12 publications

Cholinesterase Inhibitors for the Treatment of Alzheimer's Disease:

Cholinesterase Inhibitors for the Treatment of Alzheimer's Disease:

Extract of Ginkgo biloba EGb761 Facilitates Extinction of Conditioned Fear Measured by Fear-Potentiated Startle

Phytochemical Screening and Acetylcholinesterase and Butyrylcholinesterase Inhibitory and Thrombolytic Activities of Grewia abutilifolia Vent. & Juss. Leaf

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