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Donepezil, but not galantamine, blocks muscarinic receptor‐mediated in vitro and in vivo responses

We have found that galantamine, but not donepezil, reversed isolation rearing‐induced deficits of prepulse inhibition (PPI) via an activation of muscarinic M1 receptors. To explain this difference, the present study examined the effects of these acetylcholinesterase inhibitors on muscarinic receptor‐mediated responses in in vitro and in vivo systems. Ca2+‐imaging study showed that donepezil, but not galantamine, blocked a muscarinic agonist carbachol‐induced increase in intracellular Ca2+ levels in SH‐SY5Y cells. Moreover, a microdialysis study showed that intraperitoneal administration of donepezil, but not galantamine, attenuated a preferential M1 receptor agonist Ndesmethylclozapine‐induced increase in dopamine release in mouse cerebral cortex. These results suggest that donepezil, but not galantamine, has an ability to block muscarinic receptor function and imply that the differential effects may be responsible for the difference in the effects on isolation rearing‐induced deficits of PPI between these drugs. Synapse, 2011. © 2011 Wiley‐Liss, Inc.