In the brain of @entity195 @entity1 , down-regulation of both cholinergic and glutamatergic systems have been found and is thought to play an important role in @entity73 , learning, and memory. @entity45920 is a @entity29276 -related nootropic drug exhibiting various pharmacological actions such as a cognitive-enhancing effect. The present study was undertaken to elucidate mechanisms underlying the action of @entity45920 on glutamatergic receptors and intracellular protein kinases. @entity1024 ( @entity143 )-evoked currents were recorded from @entity35 cortical neurons in long-term cultured primary neurons using the whole-cell patch-clamp technique. @entity143 -evoked currents were greatly and reversibly potentiated by bath application of @entity45920 , resulting in a bell-shaped dose-response curve. The maximum potentiation of 170% relative to the control was produced at 10 nM. Treatment with an inhibitor of the @entity2228 binding site of the @entity143 receptor, @entity45606 , at 1   M prevented augmentation of @entity143 -evoked currents by @entity45920 . In @entity35 hippocampal @entity1249 slices, field excitatory postsynaptic potentials were recorded by stimulation of Schaffer collateral/commissural pathways. @entity45920 treatment significantly enhanced long-term potentiation (LTP) with the same bell-shaped dose-response curve. Furthermore, @entity45920 -induced LTP enhancement was closely associated with @entity460 /calmodulin-dependent protein kinase II (CaMKII) activation with concomitant increase in phosphorylation of @entity140 -type @entity2227 receptor subunit 1 ( @entity4860 ) (Ser-831) as a postsynaptic CaMKII substrate. In conclusion, @entity45920 enhances @entity143 -receptor function through stimulation of its @entity2228 binding site and @entity45920 -induced CaMKII activation likely contributes to improvement of cognition, learning, and memory.

Pharmacological study on Alzheimer's drugs targeting XXXX /calmodulin-dependent protein kinase II.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity1024 :: ('CHEBI:31882', 'Chemical') :: ['N-Methyl-D-aspartate'] @entity45920 :: ('MESH:C058876', 'Chemical') :: ['nefiracetam', 'Nefiracetam'] @entity2227 :: ('CHEBI:29987', 'Chemical') :: ['glutamate'] @entity2228 :: ('CHEBI:57305', 'Chemical') :: ['glycine'] @entity1249 :: ('310218(Tax:10116)', 'Gene') :: ['CA1'] @entity73 :: ('MESH:D003072', 'Disease') :: ['impairment of cognition'] @entity45606 :: ('MESH:C057013', 'Chemical') :: ['7-chlorokynurenic acid'] @entity4860 :: ('50592(Tax:10116)', 'Gene') :: ['GluA1'] @entity29276 :: ('MESH:C032519', 'Chemical') :: ['pyrrolidine'] @entity143 :: ('CHEBI:6121', 'Chemical') :: ['NMDA'] @entity460 :: ('MESH:D002118', 'Chemical') :: ['calcium'] @entity195 :: ('MESH:D000544', 'Disease') :: ["Alzheimer's disease"] @entity35 :: ('10116', 'Species') :: ['rat'] @entity140 :: ('MESH:D018350', 'Chemical') :: ['AMPA']
@entity460 :: (MESH:D002118,Chemical) :: ['calcium']
