PMID- 16740621
OWN - NLM
STAT- MEDLINE
DCOM- 20061010
LR  - 20121115
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 318
IP  - 3
DP  - 2006 Sep
TI  - Enhancement of antidepressant-like effects but not brain-derived neurotrophic 
      factor mRNA expression by the novel N-methyl-D-aspartate receptor antagonist 
      neramexane in mice.
PG  - 1128-36
AB  - Improved efficacy in the treatment of depression may be achieved by the combined 
      use of several antidepressants. In the present study, acute administration of the 
      novel N-methyl-D-aspartate (NMDA) receptor antagonist neramexane, as well as the 
      representative antidepressants imipramine, fluoxetine, and venlafaxine, shortened 
      the duration of immobility in the mouse tail suspension test with a minimal 
      effective dose of 5 mg/kg. When tested in combination, the antidepressant-like 
      effects of 5 mg/kg imipramine, 20 mg/kg fluoxetine, and 5 mg/kg venlafaxine were 
      potentiated by neramexane (2.5 mg/kg), a dose that alone did not produce a 
      significant effect on the duration of immobility. These effects seemed to be 
      specific, because they were not accompanied by significant effects on locomotor 
      activity. The enhanced antidepressant-like activity produced with the different 
      combinations was not synergistic as determined by comparing the theoretical and 
      observed ED(50) values for each combination. In separate experiments, Northern 
      blot analysis showed that a 14-day treatment with imipramine (10 mg/kg b.i.d.) 
      increased brain-derived neurotrophic factor (BDNF) mRNA expression in the cortex, 
      whereas neramexane (5 mg/kg b.i.d.) decreased it. Combined treatment produced no 
      effect on BDNF mRNA expression. Mice treated with imipramine or neramexane for 14 
      days and tested shortly after the last dose demonstrated significant shortening 
      of immobility, and the combined treatment produced an even greater 
      antidepressant-like effect. Together, these data support the view that NMDA 
      receptor antagonists enhance the potency of antidepressants, but they leave open 
      the question as to whether enhanced BDNF expression is a necessary feature of the 
      antidepressant-like effect.
FAU - Kos, Tomasz
AU  - Kos T
AD  - Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna St., 31-343 
      Krakow, Poland.
FAU - Legutko, Beata
AU  - Legutko B
FAU - Danysz, Wojciech
AU  - Danysz W
FAU - Samoriski, Gary
AU  - Samoriski G
FAU - Popik, Piotr
AU  - Popik P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060601
PL  - United States
TA  - J Pharmacol Exp Ther
JT  - The Journal of pharmacology and experimental therapeutics
JID - 0376362
RN  - 0 (Antidepressive Agents)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cyclopentanes)
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 856DX0KJ84 (neramexane)
SB  - IM
MH  - Animals
MH  - Antidepressive Agents/*pharmacology
MH  - Brain-Derived Neurotrophic Factor/*genetics
MH  - Cyclopentanes/*pharmacology
MH  - Excitatory Amino Acid Antagonists/*pharmacology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - RNA, Messenger/*analysis
MH  - Receptors, N-Methyl-D-Aspartate/*antagonists & inhibitors
EDAT- 2006/06/03 09:00
MHDA- 2006/10/13 09:00
CRDT- 2006/06/03 09:00
PHST- 2006/06/03 09:00 [pubmed]
PHST- 2006/10/13 09:00 [medline]
PHST- 2006/06/03 09:00 [entrez]
AID - jpet.106.103697 [pii]
AID - 10.1124/jpet.106.103697 [doi]
PST - ppublish
SO  - J Pharmacol Exp Ther. 2006 Sep;318(3):1128-36. doi: 10.1124/jpet.106.103697. Epub 
      2006 Jun 1.