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P2‐207: Discovery of a highly M5‐preferring muscarinic acetylcholine receptor allosteric potentiator
Author(s) -
Bridges Thomas M.,
Marlo Joy E.,
Niswender Colleen M.,
Gentry Patrick R.,
Weaver C. David,
Conn P. Jeffrey,
Lindsley Craig W.
Publication year - 2009
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2009.04.520
Subject(s) - potentiator , allosteric regulation , muscarinic acetylcholine receptor , acetylcholine , pharmacology , muscarinic acetylcholine receptor m1 , muscarinic acetylcholine receptor m5 , muscarinic acetylcholine receptor m4 , chemistry , muscarinic acetylcholine receptor m3 , muscarinic acetylcholine receptor m2 , long term potentiation , neuroscience , receptor , biology , biochemistry
by immunocytochemical staining. Results: Preliminary study of VSV replication in the PBLs of Alzheimer’s disease patients showed a high sensitivity to infection, except of PBL those under donepezil therapy.The PBL resistance stimulated us to study the effect of donepezil on innate immunity. Donepezil inhibited VSV replication in the leukocytes of healthy blood donors but influence on infection on infection in L929 and A 549 cells was not shown.The effect was dose dependent and individually differentiated.The production of TNF alfa and IFNs was reduced in infected leukocytes in a‘dose-dependent manner in the PBLs of the healthy donors and of AD patients.NFkB activation was also reduced by donepezil. Conclusions: Donepezil regulate two mechanisms of innate immunity of leukocytes:resistance to viruses and cytokine production.