title: NMDA-NR2B subtype selectivity of stereoisomeric 2-(1,2,3,4-tetrahydro-1-isoquinolyl)ethanol derivatives.
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.
authors.affiliation: Department Pharmazie-Zentrum für Pharmaforschung, Ludwig-Maximilians-Universität München, Butenandtstr. 5-13, D-81377 München, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Höfner
authors.forename: Cornelia E
authors.initials: CE
authors.lastname: Hoesl
authors.forename: Chris
authors.initials: C
authors.lastname: Parsons
authors.forename: Günther
authors.initials: G
authors.lastname: Quack
authors.forename: Klaus T
authors.initials: KT
authors.lastname: Wanner
mesh_terms: D001665:Binding Sites; D016291:Dizocilpine Maleate / Q000493:pharmacokinetics; D000431:Ethanol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000494:pharmacology*; D007700:Kinetics; D008958:Models, Molecular; D015394:Molecular Structure; D015221:Potassium Channels / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism
chemical_list: C504179:2-(1,2,3,4-tetrahydro-1-isoquinolyl)ethanol; D018691:Excitatory Amino Acid Antagonists; D007546:Isoquinolines; C121001:NR2B NMDA receptor; D015221:Potassium Channels; D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol; D016291:Dizocilpine Maleate