PMID- 20659453
OWN - NLM
STAT- MEDLINE
DCOM- 20101001
LR  - 20211020
IS  - 1090-2430 (Electronic)
IS  - 0014-4886 (Print)
IS  - 0014-4886 (Linking)
VI  - 225
IP  - 2
DP  - 2010 Oct
TI  - Lack of efficacy of NMDA receptor-NR2B selective antagonists in the R6/2 model of 
      Huntington disease.
PG  - 402-7
LID - 10.1016/j.expneurol.2010.07.015 [doi]
AB  - N-methyl-D-aspartate receptor (NMDAR) mediated excitotoxicity is a probable 
      proximate mechanism of neurodegeneration in Huntington disease (HD). Striatal 
      neurons express the NR2B-NMDAR subunit at high levels, and this subunit is 
      thought to be instrumental in causing excitotoxic striatal neuron injury. We 
      evaluated the efficacy of 3 NR2B-selective antagonists in the R6/2 transgenic 
      fragment model of HD. We evaluated ifenprodil (10 mg/kg; 100 mg/kg), RO25,6981 
      (10 mg/kg), and CP101,606 (30 mg/kg). Doses were chosen on the basis of pilot 
      acute maximally tolerated dose studies. Mice were treated with subcutaneous 
      injections twice daily. Outcomes included survival; motor performance declines 
      assessed with the rotarod, balance beam task, and activity measurements; and 
      post-mortem striatal volumes. No outcome measure demonstrated any benefit of 
      treatments. Lack of efficacy of NR2B antagonists in the R6/2 model has several 
      possible explanations including blockade of beneficial NMDAR mediated effects, 
      inadequacy of the R6/2 model, and the existence of multiple proximate mechanisms 
      of neurodegeneration in HD.
CI  - Published by Elsevier Inc.
FAU - Tallaksen-Greene, Sara J
AU  - Tallaksen-Greene SJ
AD  - Geriatrics Research, Education, and Clinical Center, VAAAHS, Ann Arbor, MI 48105, 
      USA.
FAU - Janiszewska, Anita
AU  - Janiszewska A
FAU - Benton, Kasha
AU  - Benton K
FAU - Ruprecht, Lech
AU  - Ruprecht L
FAU - Albin, Roger L
AU  - Albin RL
LA  - eng
GR  - R03 NS054810/NS/NINDS NIH HHS/United States
GR  - R21 NS059537/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100724
PL  - United States
TA  - Exp Neurol
JT  - Experimental neurology
JID - 0370712
RN  - 0 (Phenols)
RN  - 0 (Piperidines)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (Ro 25-6981)
RN  - BD2A56I30W (traxoprodil mesylate)
RN  - R8OE3P6O5S (ifenprodil)
SB  - IM
MH  - Animals
MH  - Corpus Striatum/*drug effects/pathology
MH  - Disease Models, Animal
MH  - Female
MH  - Huntington Disease/*drug therapy/pathology
MH  - Kaplan-Meier Estimate
MH  - Male
MH  - Mice
MH  - Motor Activity/*drug effects
MH  - Organ Size
MH  - Phenols/pharmacology/therapeutic use
MH  - Piperidines/pharmacology/therapeutic use
MH  - Receptors, N-Methyl-D-Aspartate/*antagonists & inhibitors
MH  - Sex Factors
MH  - Treatment Outcome
PMC - PMC2939157
MID - NIHMS226010
EDAT- 2010/07/28 06:00
MHDA- 2010/10/05 06:00
PMCR- 2011/10/01
CRDT- 2010/07/28 06:00
PHST- 2010/05/05 00:00 [received]
PHST- 2010/07/02 00:00 [revised]
PHST- 2010/07/19 00:00 [accepted]
PHST- 2010/07/28 06:00 [entrez]
PHST- 2010/07/28 06:00 [pubmed]
PHST- 2010/10/05 06:00 [medline]
PHST- 2011/10/01 00:00 [pmc-release]
AID - S0014-4886(10)00253-0 [pii]
AID - 10.1016/j.expneurol.2010.07.015 [doi]
PST - ppublish
SO  - Exp Neurol. 2010 Oct;225(2):402-7. doi: 10.1016/j.expneurol.2010.07.015. Epub 
      2010 Jul 24.