Donepezil- and scopolamine-induced rCMRglu changes assessed by PET in conscious rhesus monkeys.
OBJECTIVE
[(18)F]Fluoro-2-deoxyglucose positron emission tomography (FDG-PET) is a useful tool for measuring the regional cerebral metabolic rate of glucose (rCMRglu), which is an index of neuronal activity. Donepezil, an acetylcholine esterase inhibitor (AChEI), has been recommended as a treatment option for patients with Alzheimer's disease (AD). We aimed to characterize the effects of donepezil on rCMRglu using FDG-PET in non-human primates.


METHODS
We investigated the effects of administration of donepezil (500 microg/kg, i.m.), the non-selective muscarinic ACh receptor antagonist scopolamine (30 microg/kg, i.m.), and the coadministration of both drugs on the rCMRglu of conscious young rhesus monkeys.


RESULTS
Donepezil increased the rCMRglu in all regions of interest except in the thalamus. Scopolamine treatment also increased the rCMRglu in all regions of interest except the cerebellum and thalamus. However, these effects disappeared with coadministration of the drugs.


CONCLUSIONS
This PET study showed that administration of donepezil or scopolamine alone increased the rCMRglu in conscious rhesus monkeys. We also found that the donepezil-induced increase was abolished by simultaneous administration of scopolamine, suggesting that muscarinic ACh receptor function plays an important role in the effect of donepezil.
Asai
Makoto
M
The Medical and Pharmacological Research Center Foundation, Hakui, Ishikawa, Japan. makoto.asai@jp.astellas.com
Fujikawa
Akihiko
A
Noda
Akihiro
A
Miyoshi
Sosuke
S
Matsuoka
Nobuya
N
Nishimura
Shintaro
S
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000187:drug effects* / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D003243:Consciousness; D000077265:Donepezil; D004338:Drug Combinations; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism*; D007189:Indans / Q000008:administration & dosage / Q000494:pharmacology*; D008253:Macaca mulatta; D008297:Male; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology*; D049268:Positron-Emission Tomography; D012601:Scopolamine / Q000008:administration & dosage / Q000494:pharmacology*
D002800:Cholinesterase Inhibitors; D004338:Drug Combinations; D007189:Indans; D010880:Piperidines; D019788:Fluorodeoxyglucose F18; D000077265:Donepezil; D012601:Scopolamine; D005947:Glucose