Abstract
Enantiopure 2-(1,2,3,4-tetrahydro-1-isoquinolyl)ethanol derivatives were tested for their affinity to the ifenprodil binding site of the NMDA receptor, their potency to inhibit [3H]MK801 binding and their NMDA-NR2B subtype selectivity. The (1S,1'S)-configurated series displayed the highest affinity to the ifenprodil binding site. A reasonable potency and NMDA-NR2B subtype selectivity was found for (1S,1'S)-4c (R1=Me, R2=OMe). A high affinity to HERG K+ channels, however, suggests that (1S,1'S)-4c may involve an increased risk of cardiovascular side effects.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Binding Sites
-
Dizocilpine Maleate / pharmacokinetics
-
Ethanol / analogs & derivatives*
-
Ethanol / chemical synthesis
-
Ethanol / pharmacology*
-
Excitatory Amino Acid Antagonists / pharmacology*
-
Isoquinolines / chemical synthesis*
-
Isoquinolines / pharmacology*
-
Kinetics
-
Models, Molecular
-
Molecular Structure
-
Potassium Channels / physiology
-
Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
-
Stereoisomerism
Substances
-
2-(1,2,3,4-tetrahydro-1-isoquinolyl)ethanol
-
Excitatory Amino Acid Antagonists
-
Isoquinolines
-
NR2B NMDA receptor
-
Potassium Channels
-
Receptors, N-Methyl-D-Aspartate
-
Ethanol
-
Dizocilpine Maleate