Abstract:
:Donepezil is a selective inhibitor of acetylcholinesterase (AChE) clinically used for treating Alzheimer's disease. Cholinergic effects after short-term exposure of donepezil (up to 12 h) have been extensively studied in rats, but few have addressed the potential long-term effects. After 14 days administration (1x3 mg/kg, decapitation 4 h after the last injection) the cerebral acetylcholine level was increased by 35% and the AChE activity was decreased by 66% and 32% in brain and blood, respectively. No change was detected in choline acetyltransferase activity, or the levels of vesicular acetylcholine transporter, choline transporter, or muscarinic receptors. Expression of various cholinergic genes was unaffected. Preliminary results of AChE activity in human blood showed 60-97% and 43-89% of pre-exposed level after one and three days of donepezil administration (5 mg daily), respectively. In conclusion, donepezil exposure in rats at doses that do not inhibit brain AChE continuously during the day, will not lead to tolerance development.
journal_name
Neurochem Resjournal_title
Neurochemical researchauthors
Haug KH,Bogen IL,Osmundsen H,Walaas I,Fonnum Fdoi
10.1007/s11064-005-8828-6keywords:
subject
Has Abstractpub_date
2005-12-01 00:00:00pages
1511-20issue
12eissn
0364-3190issn
1573-6903journal_volume
30pub_type
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