UNASSIGNED: Drugs activating the sigma-1 (  1) chaperone protein are anti- @entity2730 and neuroprotective in neurodegenerative pathologies like @entity195 ( @entity195 ). Since these so-called   1 receptor (  1R) agonists modulate cholinergic and glutamatergic systems in a variety of physiological responses, we addressed their putative additive/synergistic action in combination with cholinergic or glutamatergic drugs. The selective   1 agonist @entity27180 , or the non-selective   1 drug @entity68303 was combined with the @entity4360 inhibitor @entity8124 or the @entity3391 receptor antagonist @entity3393 in the nontransgenic @entity19 model of @entity195 -like @entity2414 induced by intracerebroventricular injection of oligomeric Ab25-35 peptide. Two behavioral tests, spontaneous alternation and passive avoidance response, were used in parallel and both protective and symptomatic effects were examined. After determination of the minimally active doses for each compound, the combinations were tested and the combination index (CI) calculated. Combinations between the   1 agonists and @entity8124 showed a synergic protective effect, with CI<1, whereas the combinations with @entity3393 showed an antagonist effect, with CI>1. Symptomatic effects appeared only additive for all combinations, with CI=1. A pharmacological analysis of the @entity27180 + @entity8124 combination revealed that the synergy could be due to an inter-related mechanism involving a7 nicotinic ACh receptors and   1R. These results demonstrated that   1 drugs do not only offer a protective potential alone but also in combination with other therapeutic agents. The nature of neuromodulatory molecular chaperone of the   1R could eventually lead to synergistic combinations.

Protection by sigma-1 receptor agonists is synergic with @entity8124 , but not with @entity3393 , in a @entity19 model of amyloid-induced XXXX .

@entity2414 :: ('MESH:D008569', 'Disease') :: ['memory impairments'] @entity27180 :: ('MESH:C071738', 'Chemical') :: ['PRE-084'] @entity19 :: ('10090', 'Species') :: ['mouse'] @entity3391 :: ('D016202', 'Chemical') :: ['NMDA'] @entity2730 :: ('MESH:D000647', 'Disease') :: ['amnesic'] @entity3393 :: ('MESH:D008559', 'Chemical') :: ['memantine'] @entity4360 :: ('11423(Tax:10090)', 'Gene') :: ['acetylcholinesterase'] @entity195 :: ('MESH:D000544', 'Disease') :: ['AD', "Alzheimer's disease"] @entity8124 :: ('MESH:C076946', 'Chemical') :: ['donepezil'] @entity68303 :: ('MESH:C568535', 'Chemical') :: ['ANAVEX2-73']
@entity2414 :: (MESH:D008569,Disease) :: ['memory impairments']
