Acetylcholinesterase inhibition increases in vivo N-(2-[F-18]fluoroethyl)-4-piperidyl benzilate binding to muscarinic acetylcholine receptors

Although the inhibition of acetylcholinesterase remains the primary treatme nt of Alzheimer's disease, little is known of the results of increased acet ylcholine levels on muscarinic receptor occupancy or function. Using N-(2-[ F-18]fluoroethyl)-4-piperidyl benzilate ([F-18]FEPB), a moder ate affinity (K-i = 1.7 nmol/L) nonsubtype-selective muscarinic receptor antagonist. the authors examined the sensitivity of equilibrium in vivo radioligand bindin g 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 increase in N-(2-[F-18]fluo roethyl)-4-piperidyl benzilate binding to muscarinic cholinergic receptors. reaching a maximum increase of 90% in the striatum at a dose of 5 mg/kg in traperitoneally. Constant infusion of physostigmine at a dosage of 250 mug/ kg/min produced an identical increase in radioligand binding. This agonist- induced increase of in vivo mAChR radioligand binding offers a new method f or monitoring of the efficacy of acetylcholinesterase inhibitors or other d rugs to enhance acetylcholine actions at the muscarinic receptors.