Different pharmacology of @entity30182 at @entity1 and XXXX M2 and M 4 mAChRs in neocortex.

@entity1 @entity308 @entity3264 @entity1246 @entity16 @entity18380 @entity161 @entity302 @entity195 @entity35 @entity3451 @entity30182 @entity5402 @entity934
Cholinergic transmission plays a pivotal role in learning, memory and cognition, and disturbances of cholinergic transmission have been implicated in @entity16 including @entity195 , @entity302 and @entity161 . Pharmacological alleviation of these diseases by drugs including @entity30182 ( @entity18380 ), promising in animal models, often fails in @entity1 . We therefore compared the effects of @entity18380 on glutamatergic and GABAergic transmission in slices from @entity35 and @entity1 neocortex. We used @entity5402 (CCh; an established agonist at metabotropic muscarinic @entity934 ( @entity3451 ) receptors (mAChRs)) as a reference. Standard electrophysiological methods including intracellular and field potential recordings were used. In the @entity35 neocortex, @entity18380 prevented the CCh-induced decrease of GABAA and GABAB receptor-mediated responses but not the CCh-induced increase of the @entity308 . @entity18380 reduced neither the amplitude of the excitatory postsynaptic potentials (EPSP) nor antagonized the CCh-induced @entity308 of EPSP. In the @entity1 neocortex, however, @entity18380 failed to prevent CCh-induced decrease of the GABAB responses and directly reduced the amplitude of EPSP. These data suggest distinct effects of @entity18380 in @entity35 and @entity1 at M2 and M4 mAChRs underlying presynaptic modulation of @entity1246 and @entity3264 release, respectively. In particular, @entity18380 might be a M2 mAChR antagonist in the @entity35 but has no activity at this receptor in @entity1 neocortex. However, @entity18380 has an agonistic effect at M4 mAChR in the @entity1 but no such effect in the @entity35 neocortex. The present study confirms that pharmacology at mAChRs can differ between species and emphasizes the need of studies in @entity1 tissue.
