Acetylcholinesterase inhibition increases in vivo N-(2-[18F]fluoroethyl)-4-piperidyl benzilate binding to muscarinic acetylcholine receptors.
Although the inhibition of acetylcholinesterase remains the primary treatment of Alzheimer's disease, little is known of the results of increased acetylcholine levels on muscarinic receptor occupancy or function. Using N-(2-[18F]fluoroethyl)-4-piperidyl benzilate ([18F]FEPB), a moderate affinity (Ki = 1.7 nmol/L) nonsubtype-selective muscarinic receptor antagonist, the authors examined the sensitivity of equilibrium in vivo radioligand binding in rat brain with changes in endogenous acetylcholine levels produced by treatments with acetylcholinesterase inhibitors. Phenserine administration 30 minutes before resulted in a dose-dependent into muscarinic cholinergic receptors, reaching a maximum increase of 90% in the striatum at a dose of 5 mg/kg intraperitoneally. Constant infusion of physostigmine at a dosage of 250 microg/kg/min produced an identical increase in radioligand binding. This agonist-induced increase of in vivo mAChR radioligand binding offers a new method for monitoring of the efficacy of acetylcholinesterase inhibitors or other drugs to enhance acetylcholine actions at the muscarinic receptors.
Skaddan
M B
MB
Department of Radiology, University of Michigan Medical School, Ann Arbor 48109-0552, USA.
Kilbourn
M R
MR
Snyder
S E
SE
Sherman
P S
PS
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001561:Benzilates / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D003342:Corpus Striatum / Q000378:metabolism; D005462:Fluorine Radioisotopes; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D018727:Muscarinic Antagonists / Q000378:metabolism*; D010830:Physostigmine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D010880:Piperidines / Q000378:metabolism*; D051381:Rats; D011976:Receptors, Muscarinic / Q000378:metabolism*
D001561:Benzilates; D002800:Cholinesterase Inhibitors; D005462:Fluorine Radioisotopes; D018727:Muscarinic Antagonists; C416657:N-(2-fluoroethyl)-4-piperidyl benzilate; D010880:Piperidines; D011976:Receptors, Muscarinic; D010830:Physostigmine; D000109:Acetylcholine; C092280:phenserine