Inhibitory action off E2020, a novel acetylcholinesterase inhibitor, on cholinesterase in aged rats

Yamanishi, Yoshihiro; Ogura, H.; Kosasa, Takashi; Uchikoshi, Kumi; Sawa, Yuko; Yamatsu, Kiyomi

doi:10.1016/0014-2999(90)92281-m

Cited by 11 publications

(5 citation statements)

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“…The results of this in vivo treatment (Fig. (2 2 )) indicate that all three compounds caused a dose-dependent inhibition of brain AChE activity, and that donepezil appeared to be a more potent inhibitor than either PHY or tacrine [88]. concentration of ACh in the brain.…”

Section: Effects On Cholinesterase Activitymentioning

confidence: 87%

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Donepezil Hydrochloride (E2020) and Other Acetylcholinesterase Inhibitors

Sugimoto

Yamanishi²,

Iimura³

et al. 2000

Current Medicinal Chemistry

285

165

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A wide range of evidence shows that acetylcholinesterase (AChE) inhibitors can interfere with the progression of Alzheimer's disease (AD). The successful development of these compounds was based on a well-accepted theory that the decline in cognitive and mental functions associated with AD is related to the loss of cortical cholinergic neurotransmission. The earliest known AChE inhibitors, namely, physostigmine and tacrine, showed modest improvement in the cognitive function of Alzheimer's patients. However, clinical studies show that physostigmine has poor oral activity, brain penetration and pharmacokinetic parameters while tacrine has hepatotoxic liability. Studies were then focused on finding a new type of acetylcholinesterase inhibitor that would overcome the disadvantages of these two compounds. Donepezil hydrochloride inaugurates a new class of AChE inhibitors with longer and more selective action with manageable adverse effects. Currently, there are about 19 new Alzheimer's drugs in various phases of clinical development.

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Section: Effects On Cholinesterase Activitymentioning

confidence: 87%

“…The concentration of ACh in the hippocampus was then determined by HPLC analysis. The hippocampus was chosen for analysis in this study because of its involvement in memory-related functions [88]. The results (Fig.…”

Section: (A) the Effect Of Donepezil On The Concentration Of Ach In Rmentioning

confidence: 99%

Donepezil Hydrochloride (E2020) and Other Acetylcholinesterase Inhibitors

Sugimoto

Yamanishi²,

Iimura³

et al. 2000

Current Medicinal Chemistry

285

165

View full text Add to dashboard Cite

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“…In preclinical studies, donepezil demonstrated greater specificity for rat brain AChE than plasma butyrylcholinesterase (BuChE) (IC 50 ratio BuChE/AChE: 1252) than either physostigmine (IC 50 ratio: 11.9) or tacrine (IC 50 ratio: 0.9) [ 11]. Furthermore, a study investigating the tissue distribution of cholinesterase inhibition in aged rats has shown that donepezil is specific for AChE in the brain [ 19].…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic and pharmacodynamic profile of donepezil HCl following single oral doses

Rogers

Friedhoff

1998

Brit J Clinical Pharma

126

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Aim The aim of this study was to characterize the pharmacokinetic and pharmacodynamic profile of donepezil HCl, a chemically distinct and specific acetylcholinesterase (AChE) inhibitor for the treatment of Alzheimer's disease, following administration of single oral doses. Methods This was a double-blind, randomized, single-dose, placebo-controlled, sequential-group, ascending-dose study in healthy male volunteers (n=48). Six dose levels were investigated, ranging from 0.3 to 6.0 mg. Donepezil concentrations in plasma were determined by HPLC with UV detection. Pharmacodynamic activity was determined by the radioenzymatic measurement of erythrocyte membrane acetylcholinesterase (rbc-AChE) inhibition. Results The pharmacokinetic disposition of donepezil was observed to be both linear and dose proportional following single-dose administration. The mean peak plasma concentration (C max ) of donepezil was observed at 4.1±1.5 h. The mean terminal disposition half-life was 81.5±22.0 h. The post-absorption phase of the plasma concentration-time curves for the 4.0 mg and 6.0 mg doses appeared to be biphasic, but the rate of donepezil clearance was independent of dose. Plasma concentrations for the 0.3, 0.6 and 0.9 mg dose groups were generally below the level of HPLC detection (2.0 ng ml −1 ), preventing accurate characterization of these doses.A direct correlation was observed between plasma donepezil concentrations and extent of AChE inhibition. For the 4.0 and 6.0 mg donepezil dose groups, maximal AChE inhibition ( E max ) ranged from 33% to 35% and there was significant correlation between AChE inhibition and donepezil plasma concentration ( P<0.005). Conclusions The pharmacokinetics of donepezil were found to be linear and dose proportional following the administration of single doses to healthy volunteers. A direct correlation was also observed between plasma donepezil concentrations and AChE inhibition. The extended half-life of donepezil makes it suitable for oncedaily dosing.

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“…Thus this compound may be a possible candidate for the therapeutic application in memory impairment. Similarly, the development of brain-selective acetylcholinesterase inhibitors such as ENA-713 [61] and E2020 [62] may provide serious memory-improving compounds.…”

Section: Future Possibilities To Develop Cognition-enhancing Drugsmentioning

confidence: 99%

Pharmacology of long-term potentiation

Beukers¹,

Boddeke²

1991

Pharmaceutisch Weekblad Scientific Edition

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Long-term potentiation is widely used as a model for memory formation. Recently, much information concerning this topic like the involvement of protein kinase C, arachidonic acid and N-methyl-D-aspartate receptors has been reported. In this review recent discoveries concerning long-term potentiation and the pharmacological implications for the development of cognition-enhancing drugs are discussed.

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Inhibitory action off E2020, a novel acetylcholinesterase inhibitor, on cholinesterase in aged rats

Cited by 11 publications

References 0 publications

Donepezil Hydrochloride (E2020) and Other Acetylcholinesterase Inhibitors

Donepezil Hydrochloride (E2020) and Other Acetylcholinesterase Inhibitors

Pharmacokinetic and pharmacodynamic profile of donepezil HCl following single oral doses

Pharmacology of long-term potentiation

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