PMID- 28089695
OWN - NLM
STAT- MEDLINE
DCOM- 20170907
LR  - 20180719
IS  - 1878-4216 (Electronic)
IS  - 0278-5846 (Linking)
VI  - 75
DP  - 2017 Apr 3
TI  - The pharmacology of tacrine at N-methyl-d-aspartate receptors.
PG  - 54-62
LID - S0278-5846(16)30278-0 [pii]
LID - 10.1016/j.pnpbp.2017.01.003 [doi]
AB  - The mechanism of tacrine as a precognitive drug has been considered to be complex 
      and not fully understood. It has been reported to involve a wide spectrum of 
      targets involving cholinergic, gabaergic, nitrinergic and glutamatergic pathways. 
      Here, we review the effect of tacrine and its derivatives on the NMDA receptors 
      (NMDAR) with a focus on the mechanism of action and biological consequences 
      related to the Alzheimer's disease treatment. Our findings indicate that effect 
      of tacrine on glutamatergic neurons is both direct and indirect. Direct NMDAR 
      antagonistic effect is often reported by in vitro studies; however, it is 
      achieved by high tacrine concentrations which are not likely to occur under 
      clinical conditions. The impact on memory and behavioral testing can be ascribed 
      to indirect effects of tacrine caused by influencing the NMDAR-mediated currents 
      via M1 receptor activation, which leads to inhibition of Ca(2+)-activated 
      potassium channels. Such inhibition prevents membrane repolarization leading to 
      prolonged NMDAR activation and subsequently to long term potentiation. 
      Considering these findings, we can conclude that tacrine-derivatives with dual 
      cholinesterase and NMDARs modulating activity may represent a promising approach 
      in the drug development for diseases associated with cognitive dysfunction, such 
      as the Alzheimer disease.
CI  - Copyright (c) 2017 Elsevier Inc. All rights reserved.
FAU - Horak, Martin
AU  - Horak M
AD  - Institute of Physiology, Academy of Sciences of the Czech Republic v.v.i., 
      Videnska 1083, 14220 Prague 4, Czech Republic.
FAU - Holubova, Kristina
AU  - Holubova K
AD  - National Institute of Mental Health, Topolova 748, 250 67 Klecany, Czech 
      Republic.
FAU - Nepovimova, Eugenie
AU  - Nepovimova E
AD  - Biomedical Research Centre, University Hospital Hradec Kralove, Sokolska 581, 500 
      05 Hradec Kralove, Czech Republic.
FAU - Krusek, Jan
AU  - Krusek J
AD  - Institute of Physiology, Academy of Sciences of the Czech Republic v.v.i., 
      Videnska 1083, 14220 Prague 4, Czech Republic.
FAU - Kaniakova, Martina
AU  - Kaniakova M
AD  - Institute of Physiology, Academy of Sciences of the Czech Republic v.v.i., 
      Videnska 1083, 14220 Prague 4, Czech Republic.
FAU - Korabecny, Jan
AU  - Korabecny J
AD  - Biomedical Research Centre, University Hospital Hradec Kralove, Sokolska 581, 500 
      05 Hradec Kralove, Czech Republic.
FAU - Vyklicky, Ladislav
AU  - Vyklicky L
AD  - Institute of Physiology, Academy of Sciences of the Czech Republic v.v.i., 
      Videnska 1083, 14220 Prague 4, Czech Republic.
FAU - Kuca, Kamil
AU  - Kuca K
AD  - Biomedical Research Centre, University Hospital Hradec Kralove, Sokolska 581, 500 
      05 Hradec Kralove, Czech Republic.
FAU - Stuchlik, Ales
AU  - Stuchlik A
AD  - Institute of Physiology, Academy of Sciences of the Czech Republic v.v.i., 
      Videnska 1083, 14220 Prague 4, Czech Republic.
FAU - Ricny, Jan
AU  - Ricny J
AD  - National Institute of Mental Health, Topolova 748, 250 67 Klecany, Czech 
      Republic.
FAU - Vales, Karel
AU  - Vales K
AD  - National Institute of Mental Health, Topolova 748, 250 67 Klecany, Czech 
      Republic.
FAU - Soukup, Ondrej
AU  - Soukup O
AD  - Biomedical Research Centre, University Hospital Hradec Kralove, Sokolska 581, 500 
      05 Hradec Kralove, Czech Republic. Electronic address: ondrej.soukup@fnhk.cz.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20170113
PL  - England
TA  - Prog Neuropsychopharmacol Biol Psychiatry
JT  - Progress in neuro-psychopharmacology & biological psychiatry
JID - 8211617
RN  - 0 (Cholinesterase Inhibitors)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 4VX7YNB537 (Tacrine)
SB  - IM
MH  - Animals
MH  - Cholinesterase Inhibitors/*pharmacology
MH  - Humans
MH  - Membrane Potentials/drug effects
MH  - Models, Molecular
MH  - Neurons/*drug effects
MH  - Receptors, N-Methyl-D-Aspartate/drug effects/*metabolism
MH  - Tacrine/chemistry/*pharmacology
OTO - NOTNLM
OT  - Cognition
OT  - Long term potentiation
OT  - M1 activation
OT  - Multi-target directed ligands
OT  - NMDA receptors
OT  - Tacrine
EDAT- 2017/01/17 06:00
MHDA- 2017/09/08 06:00
CRDT- 2017/01/17 06:00
PHST- 2016/10/07 00:00 [received]
PHST- 2016/12/15 00:00 [revised]
PHST- 2017/01/09 00:00 [accepted]
PHST- 2017/01/17 06:00 [pubmed]
PHST- 2017/09/08 06:00 [medline]
PHST- 2017/01/17 06:00 [entrez]
AID - S0278-5846(16)30278-0 [pii]
AID - 10.1016/j.pnpbp.2017.01.003 [doi]
PST - ppublish
SO  - Prog Neuropsychopharmacol Biol Psychiatry. 2017 Apr 3;75:54-62. doi: 
      10.1016/j.pnpbp.2017.01.003. Epub 2017 Jan 13.