PMID- 14510820
OWN - NLM
STAT- MEDLINE
DCOM- 20031125
LR  - 20190813
IS  - 0013-9580 (Print)
IS  - 0013-9580 (Linking)
VI  - 44
IP  - 10
DP  - 2003 Oct
TI  - Voltage-dependent block of N-methyl-D-aspartate receptors by the novel 
      anticonvulsant dibenzylamine, a bioactive constituent of 
      L-(+)-beta-hydroxybutyrate.
PG  - 1274-9
AB  - PURPOSE: Previously we demonstrated that L-(+)-beta-hydroxybutyrate (L-BHB), 
      acetoacetate (ACA), acetone, and dibenzylamine (DBA) were anticonvulsant in an 
      audiogenic seizure-susceptible model, and that DBA was a bioactive contaminant 
      identified in commercial lots of L-BHB. In the present study, we asked whether 
      these effects could be mediated by ionotropic glutamate or gamma-aminobutyric 
      acidA (GABAA) receptors. METHODS: We studied the effects of both stereoisomers of 
      BHB (as well as the racemate), ACA, and DBA on N-methyl-D-aspartate (NMDA), 
      alpha-amino-3-hydroxy-5methyl-4-isoxazole-proprionic acid (AMPA), and GABAA 
      receptors in cultured rodent neocortical neurons by using whole-cell 
      voltage-clamp recording techniques. RESULTS: Only L-BHB and DBA exerted a 
      concentration- and voltage-dependent block of NMDA-evoked currents, whereas none 
      of the tested substrates affected AMPA- or GABA-activated currents. The kinetics 
      of whole-cell block by L-BHB and DBA were similar, providing additional evidence 
      that DBA is responsible for the anticonvulsant activity of L-BHB. CONCLUSIONS: 
      BHB and ACA do not exert direct actions on GABAA or ionotropic glutamate 
      receptors in cultured neocortical neurons. In addition, we provide additional 
      evidence that DBA is responsible for the anticonvulsant activity of L-BHB, and 
      that this action may be mediated in part by voltage-dependent blockade of NMDA 
      receptors.
FAU - Donevan, Sean D
AU  - Donevan SD
AD  - Pfizer Global Research and Development, Ann Arbor, Michigan, USA.
FAU - White, H Steve
AU  - White HS
FAU - Anderson, Gail D
AU  - Anderson GD
FAU - Rho, Jong M
AU  - Rho JM
LA  - eng
GR  - K08 NS01974/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Epilepsia
JT  - Epilepsia
JID - 2983306R
RN  - 0 (Anticonvulsants)
RN  - 0 (Benzylamines)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 3G0YFX01C6 (dibenzylamine)
RN  - TZP1275679 (3-Hydroxybutyric Acid)
SB  - IM
MH  - 3-Hydroxybutyric Acid/metabolism/*pharmacology
MH  - Animals
MH  - Anticonvulsants/*pharmacology
MH  - Benzylamines/*pharmacology
MH  - Cells, Cultured
MH  - Dose-Response Relationship, Drug
MH  - Fetus
MH  - Mice
MH  - Neocortex/*drug effects/physiology
MH  - Patch-Clamp Techniques
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, N-Methyl-D-Aspartate/*antagonists & inhibitors/physiology
EDAT- 2003/09/27 05:00
MHDA- 2003/12/03 05:00
CRDT- 2003/09/27 05:00
PHST- 2003/09/27 05:00 [pubmed]
PHST- 2003/12/03 05:00 [medline]
PHST- 2003/09/27 05:00 [entrez]
AID - 07203 [pii]
AID - 10.1046/j.1528-1157.2003.07203.x [doi]
PST - ppublish
SO  - Epilepsia. 2003 Oct;44(10):1274-9. doi: 10.1046/j.1528-1157.2003.07203.x.