PMID- 18795266
OWN - NLM
STAT- MEDLINE
DCOM- 20090805
LR  - 20220321
IS  - 1432-2072 (Electronic)
IS  - 0033-3158 (Linking)
VI  - 202
IP  - 1-3
DP  - 2009 Jan
TI  - Evaluation of the pro-cognitive effects of the AMPA receptor positive modulator, 
      5-(1-piperidinylcarbonyl)-2,1,3-benzoxadiazole (CX691), in the rat.
PG  - 343-54
LID - 10.1007/s00213-008-1325-2 [doi]
AB  - RATIONALE: Positive allosteric modulators of the glutamatergic 
      alpha-amino-3-hydroxy-5-methyl-4-isoazolepropionic acid (AMPA) receptor do not 
      stimulate AMPA receptors directly but delay deactivation of the receptor and/or 
      slow its desensitisation. This results in increased synaptic responses and 
      enhanced long-term potentiation. Thus, it has been suggested that such compounds 
      may have utility for the treatment of cognitive impairment. OBJECTIVES: The 
      objective of the study was to investigate the effect of an AMPA positive 
      modulator, CX691, (1) in three rodent models of learning and memory, (2) on 
      neurochemistry in the dorsal hippocampus and medial prefrontal cortex following 
      acute administration, and (3) on brain-derived neurotrophic factor (BDNF) 
      messenger RNA (mRNA) expression in the rat hippocampus following acute and 
      sub-chronic administration. RESULTS: CX691 attenuated a scopolamine-induced 
      impairment of cued fear conditioning following acute administration (0.1 mg/kg 
      p.o.) and a temporally induced deficit in novel object recognition following both 
      acute (0.1 and 1.0 mg/kg p.o.) and sub-chronic (bi-daily for 7 days) 
      administration (0.01, 0.03, 0.1 mg/kg p.o.). It also improved attentional 
      set-shifting following sub-chronic administration (0.3 mg/kg p.o.). Acute CX691 
      (0.1, 0.3 and 1.0 mg/kg, p.o.) increased extracellular levels of acetylcholine in 
      the dorsal hippocampus and medial prefrontal cortex and dopamine in the medial 
      prefrontal cortex. Sub-chronic administration of CX691 (0.1 mg/kg, p.o.) elevated 
      BDNF mRNA expression in both the whole and CA(1) sub-region of the hippocampus (P 
      < 0.05). CONCLUSIONS: Collectively, these data support the pro-cognitive activity 
      reported for AMPA receptor positive modulators and suggest that these compounds 
      may be of benefit in treating disorders characterised by cognitive deficits such 
      as Alzheimer's disease and schizophrenia.
FAU - Woolley, M L
AU  - Woolley ML
AD  - Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline plc, New 
      Frontiers Science Park, Third Avenue, Harlow, Essex CM195AW, UK. 
      marie.2.woolley-roberts@gsk.com
FAU - Waters, K A
AU  - Waters KA
FAU - Gartlon, J E
AU  - Gartlon JE
FAU - Lacroix, L P
AU  - Lacroix LP
FAU - Jennings, C
AU  - Jennings C
FAU - Shaughnessy, F
AU  - Shaughnessy F
FAU - Ong, A
AU  - Ong A
FAU - Pemberton, D J
AU  - Pemberton DJ
FAU - Harries, M H
AU  - Harries MH
FAU - Southam, E
AU  - Southam E
FAU - Jones, D N C
AU  - Jones DN
FAU - Dawson, L A
AU  - Dawson LA
LA  - eng
PT  - Journal Article
DEP - 20080916
PL  - Germany
TA  - Psychopharmacology (Berl)
JT  - Psychopharmacology
JID - 7608025
RN  - 0 (1-(benzofurazan-5-ylcarbonyl)piperidine)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Muscarinic Antagonists)
RN  - 0 (Nootropic Agents)
RN  - 0 (Oxadiazoles)
RN  - 0 (Piperidines)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, AMPA)
RN  - DL48G20X8X (Scopolamine)
RN  - N9YNS0M02X (Acetylcholine)
RN  - VTD58H1Z2X (Dopamine)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
MH  - Acetylcholine/metabolism
MH  - Amygdala/physiology
MH  - Animals
MH  - Attention/drug effects
MH  - Brain-Derived Neurotrophic Factor/biosynthesis
MH  - Cognition/*drug effects
MH  - Conditioning, Operant/drug effects
MH  - Cues
MH  - Dopamine/metabolism
MH  - Fear/drug effects/psychology
MH  - Hippocampus/drug effects/metabolism
MH  - In Situ Hybridization
MH  - Male
MH  - Muscarinic Antagonists/pharmacology
MH  - Nootropic Agents/*pharmacology
MH  - Norepinephrine/metabolism
MH  - Oxadiazoles/*pharmacology
MH  - Piperidines/*pharmacology
MH  - Prefrontal Cortex/drug effects/metabolism
MH  - RNA, Messenger/biosynthesis
MH  - Rats
MH  - Receptors, AMPA/*drug effects
MH  - Recognition, Psychology/*drug effects
MH  - Scopolamine/antagonists & inhibitors/pharmacology
EDAT- 2008/09/17 09:00
MHDA- 2009/08/06 09:00
CRDT- 2008/09/17 09:00
PHST- 2008/04/22 00:00 [received]
PHST- 2008/08/31 00:00 [accepted]
PHST- 2008/09/17 09:00 [pubmed]
PHST- 2009/08/06 09:00 [medline]
PHST- 2008/09/17 09:00 [entrez]
AID - 10.1007/s00213-008-1325-2 [doi]
PST - ppublish
SO  - Psychopharmacology (Berl). 2009 Jan;202(1-3):343-54. doi: 
      10.1007/s00213-008-1325-2. Epub 2008 Sep 16.