Donepezil
From Proteopedia
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===Mechanism of Action=== | ===Mechanism of Action=== | ||
| - | Donepezil is a potent [[Acetylcholinesterase]] (AChE) inhibitor to the active site of <scene name='42/428165/Ache/6'>AChE</scene>. By inhibiting AChE, the important neurotransmitter, [[acetylcholine]], is degraded at a slower rate, helping reverse the marked decrease in neuronal function evident in [[Alzheimer's Disease]] patients. Donepezil binds along the active-site gorge, extending from the anionic subsite <scene name='42/428165/Trp_84/3'>near Trp 84</scene> to the peripheral anionic site <scene name='42/428165/Trp_279/2'>near Trp 279</scene>. Interestingly, it does not directly interact with the catalytic triad of acetylcholinesterase nor the oxyanion hole. Further, donepezil does not form any direct hydrogen bonds with AChE nor electrostatic interactions, but rather only interacts via aromatic stacking and solvent mediated interactions. It <scene name=' | + | Donepezil is a potent [[Acetylcholinesterase]] (AChE) inhibitor to the active site of <scene name='42/428165/Ache/6'>AChE</scene>. By inhibiting AChE, the important neurotransmitter, [[acetylcholine]], is degraded at a slower rate, helping reverse the marked decrease in neuronal function evident in [[Alzheimer's Disease]] patients. Donepezil binds along the active-site gorge, extending from the anionic subsite <scene name='42/428165/Trp_84/3'>near Trp 84</scene> to the peripheral anionic site <scene name='42/428165/Trp_279/2'>near Trp 279</scene>. Interestingly, it does not directly interact with the catalytic triad of acetylcholinesterase nor the oxyanion hole. Further, donepezil does not form any direct hydrogen bonds with AChE nor electrostatic interactions, but rather only interacts via aromatic stacking and solvent mediated interactions. It <scene name='42/428165/Bound/3'>primarily interacts</scene> with Glu 199, His 440, Phe 330, Trp 84, Tyr 334, Tyr 121, Phe 331, Phe 288, Ser 286, Phe 290, Arg 289, Trp 279, & Leu 282 to tightly bind to AChE<ref name="Kryger">PMID:10368299</ref>. More details can be seen at [[Aricept_Complexed_with_Acetylcholinesterase]]. |
===Pharmacokinetics=== | ===Pharmacokinetics=== | ||
Current revision
Donepezil
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