Donepezil - CAS 120014-06-4
Catalog number: 120014-06-4
Molecular Formula:
Molecular Weight:
Donepezil is a medication used in the palliative treatment of Alzheimer's disease. Donepezil is used to improve cognition and behavior of people with Alzheimer's, but does not slow the progression of or cure the disease.
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A crystalline solid
1. A gorge-spanning, high-affinity cholinesterase inhibitor to explore β-amyloid plaques
Paul W. Elsinghorst, Wolfgang Hartig, Simone Goldhammer, Jens Groscheb,c and Michael Gutschow*. Org. Biomol. Chem., 2009, 7, 3940–3946
To corroborate our initial conclusion, that 13 binds to AChE inside plaques, staining experiments were subsequently repeated in the presence and absence of fasciculin-2, a peptidic (Mr =6500 , IC50 = 24 nM), high-affinity AChE inhibitor. No significant difference in staining by 13 (6.8 mM) was observed as a result of the presence or absence of fasciculin-2(3.1 mM). A reduction in fluorescence after treatment with fasciculin-2 would have provided ultimate proof of 13 binding to AChE inside β-amyloid plaques. The unaltered observation leads to further questions, e.g. whether fasciculin-2 will penetrate into the b-amyloid plaque core, and whether fasciculin-2 can bind to AChE inside the lattice of aggregated Ab. To exclude molecular size as a question of debate, comparable experiments were carried out using donepezil hydrochloride (Mr = 416.0), which occupies the enzyme gorge in a similar fashion as expected for 13. Again, no attenuation of staining intensity caused by 13 (6.8 mM) was observed in brain samples pretreated with donepezil (145 mM) as shown in Fig.4. The same result was observed after simultaneous application of equipotent concentrations (145 mM donepezil, 6.8 mM13) or excess of donepezil (1450 mM, 6.8 mM13). Binding of 13 to AChE inside b-amyloid plaques seems therefore rather unlikely.
2. Biocentri-voltammetry for the enzyme assay: a model study
Serdar C ¸ evik, Suna Timur and Ulku Anik*. RSC Adv., 2012, 2, 4299–4303
For the inhibition study, as mentioned in the experimental, a Donepezil-based AD drug was analyzed. After the preparation of the sample that was taken from the drug, the measurement was conducted by introducing Donepezil together with ATCh and AChE in the reaction medium. Then the centrifugation was applied and the voltammogram was recorded (Fig. 7). As can be seen from the figure, a sharp decrease was obtained at the current value, demonstrating the inhibition of Donepezil. Based on the obtained current values and following the necessary formula, the inhibition was calculated as 80%.
3. An immobilization multienzyme microfluidic chip for acetylcholinesterase inhibition assay by fluorescence method
Yulan Tang, Sufang Liu,* Rongbiao Pi and Zhiyi Cheng*. RSC Adv.,2016, 6,20867–20875
The enzyme activity and inhibitor assays were carried out in prepared microchip device and described below briefly. Substrate ACh (or ACh mixed with donepezil in inhibition assay) was injected into the system from C1 and C2 (high and low concentration) to generate concentration gradient and catalyzed by immobilized enzyme in reaction wells. After incubation for 10 min, L-tyrosine/HRP mixture solution was injected from C3 and C4, and then mixed with product H2O2 through long sinuous micro-channels. Finally, the fluorescent dimer in detection chambers was quantified after 5 min.
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