Research and Development of Donepezil Hydrochloride, a New Type of Acetylcholinesterase Inhibitor

Sugimoto, Hachiro; Ogura, Hiroo; Arai, Yasuo; Iimura, Youichi; Yamanishi, Yoshihiro

doi:10.1254/jjp.89.7

Cited by 202 publications

(140 citation statements)

References 53 publications

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“…In order to determine whether a potentiating effect on the ASR (and a delayed habituation response) could also be achieved with other agents linked to memory enhancing effects, donepezil and memantine were evaluated in the assay since they act through different pharmacological mechanisms, donepezil being an acetylcholinesterase inhibitor (Sugimoto et al, 2002) and memantine an NMDA receptor antagonist (Parsons et al, 1999). Both are current therapies for Alzheimer's disease and have been shown to improve cognitive ability in Alzheimer's disease patients (Burns et al, 1999;Winblad et al, 2001Winblad et al, , 2006Peskind et al, 2006;Takeda et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Non-Associative Learning in Larval Zebrafish

Best¹,

Berghmans²,

Hunt³

et al. 2007

Neuropsychopharmacol

211

150

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Habituation, where a response is reduced when exposed to a continuous stimulus is one of the simplest forms of non-associative learning and has been shown in a number of organisms from sea slugs to rodents. However, very little has been reported in the zebrafish, a model that is gaining popularity for high-throughput compound screens. Furthermore, since most of the studies involving learning and memory in zebrafish have been conducted in adults, we sought to determine if zebrafish larvae could display non-associative learning and whether it could be modulated by compounds identified in previous rodent studies. We demonstrated that zebrafish larvae (7 days post fertilization) exhibit iterative reduction in a startle response to a series of acoustic stimuli. Furthermore, this reduction satisfied criteria for habituation: spontaneous recovery, more rapid reductions in startle to shorter intertrial intervals and dishabituation. We then investigated the pathways mediating this behavior using established compounds in learning and memory. Administration of rolipram (PDE4 inhibitor), donepezil (acetylcholinesterase inhibitor), and memantine (N-methyl-D-aspartic acid (NMDA) receptor antagonist) all increased the acoustic startle response and decreased habituation in the larvae, similar to previous rodent studies. Further studies demonstrated that NMDA blocked the memantine response and the effect of donepezil was blocked by mecamylamine but not atropine suggesting that the donepezil response was mediated by nicotinic rather than muscarinic receptors. Zebrafish larvae possess numerous advantages for medium to high-throughput screening; the model described herein therefore offers the potential to screen for additional compounds for further study on cognition function.

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Section: Discussionmentioning

confidence: 99%

Non-Associative Learning in Larval Zebrafish

Best¹,

Berghmans²,

Hunt³

et al. 2007

Neuropsychopharmacol

211

150

View full text Add to dashboard Cite

show abstract

“…Cholinergic neurons degenerate in patients with Alzheimer's disease as well as senile dementia, and, importantly, the degree of degeneration highly correlates with functional loss in these disorders (Davies and Maloney, 1976;Perry et al, 1978a, b). Clinical trials revealed that donepezil (Aricept, previously E2020, Pfizer), a selective noncompetitive inhibitor of acetylcholinesterase (AChE; see Sugimoto et al (2002) for a review), had cognitive benefits in Alzheimer's disease patients afflicted with mild to moderate degrees of dementia (Mintzer and Kershaw, 2003). Presently donepezil is used to treat cognitive deficits associated with Alzheimer's disease (Rogers and Friedhoff, 1998;Doody, 1999;Grutzendler and Morris, 2001).…”

Section: Introductionmentioning

confidence: 99%

Combination of Rimonabant and Donepezil Prolongs Spatial Memory Duration

Wise

Iredale

Stokes

et al. 2007

Neuropsychopharmacol

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The observations that the cannabinoid 1 (CB 1 ) receptor antagonist/inverse agonist, rimonabant, and the selective noncompetitive inhibitor of acetylcholinesterase (AChE), donepezil, improve performance in a variety of animal memory models, suggest that these neurochemical systems play integral roles in cognition. The present study tested whether each of these agents administered alone or in combination will prolong the duration of spatial memory. Rats were trained in a two-phase radial-arm maze procedure, consisting of acquisition and retrieval tests, which were separated by an 18 h delay. Each drug was administered 30 min before the acquisition phase, immediately after the acquisition phase, or 30 min before the retrieval test to assess acquisition/consolidation, consolidation, and retrieval mnemonic processes, respectively. Rimonabant or donepezil administered before the acquisition phase, but not immediately after acquisition or before retrieval, led to a significant decrease in the number of errors committed during the retrieval test. Combined administration of subthreshold doses of rimonabant and donepezil that had no discernable effects on performance when given alone, enhanced memory.These results taken together demonstrate that the delay radial-arm maze task is sufficiently sensitive to detect memory enhancing effects of these drugs. Moreover, these findings suggest that combined administration of subthreshold doses of rimonabant and donepezil can improve memory and may represent a novel approach to treat cognitive deficits associated with neurodegenerative disorders.

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“…In particular, it is useful for prevention and treatment of Alzheimer's disease by virtue of its acetyl cholinesterase inhibitory action 22 . There are many processes described mainly in patent literature [23][24][25][26][27][28][29][30][31][32] for producing (4) and its pharmaceutically acceptable salts. Complete chemo-selectivity is unlikely, because the starting compound (1) has more than one functionality susceptible to hydrogenation.…”

Section: Introductionmentioning

confidence: 99%

reKinetics and Mass Transfer in the Hydrogenation of 2-((1-benzyl-1,2,3,6-tetrahydropyridin-4-yl)methylene)-5,6-dimethoxy- -2,3-dihydroinden-1-one hydrochloride over Pt/C Catalyst

Zrnčević¹

2015

Chem.Biochem.Eng.Q.

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The liquid phase hydrogenation of 2-((1-benzyl-1,2,3,6-tetrahydropyridin-4-yl) methylene)-5,6-dimethoxy-2,3-dihydroinden-1-one hydrochloride (1) over a 5 % Pt/C industrial catalyst was studied experimentally in a batch slurry reactor using methanol as a solvent. The catalyst was characterized by the adsorption techniques for specific surface area and pore volume, and by XRD for crystallinity. To investigate the intrinsic kinetics of the reaction, the effect of temperature, catalyst loading, hydrogen partial pressure and (1) concentration on the initial rate of hydrogenation was studied. The analysis of initial rate data showed that the gas-liquid, liquid-solid, and intraparticle mass-transfer resistances were not significant. The reaction scheme of (1) hydrogenation was proposed for the kinetic modelling. Apparent rate constants for all hydrogenation steps were calculated using a first order kinetic approach resulting in good agreement between the experimentally obtained and predicted concentrations. From the temperature dependence of rate constants, the activation energies of various reaction steps were calculated. The averaged activation energy of these steps was found to be 31.1 kJ mol -1 .

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Research and Development of Donepezil Hydrochloride, a New Type of Acetylcholinesterase Inhibitor

Cited by 202 publications

References 53 publications

Non-Associative Learning in Larval Zebrafish

Non-Associative Learning in Larval Zebrafish

Combination of Rimonabant and Donepezil Prolongs Spatial Memory Duration

reKinetics and Mass Transfer in the Hydrogenation of 2-((1-benzyl-1,2,3,6-tetrahydropyridin-4-yl)methylene)-5,6-dimethoxy- -2,3-dihydroinden-1-one hydrochloride over Pt/C Catalyst

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