Antagonist properties of the stereoisomers of ifenprodil at NR1A/NR2A and NR1A/NR2B subtypes of the NMDA receptor expressed in Xenopus oocytes.
The NMDA receptor antagonist ifenprodil contains two asymmetric centres which give rise to four stereoisomeric forms of this molecule. The inhibitory effects of each of these stereoisomers on recombinant NMDA receptors expressed from NR1A/NR2A and NR1A/NR2B subunit combinations were studied in Xenopus oocytes by voltage-clamp recording. All four ifenprodil stereoisomers were potent antagonists at NR1A/NR2B (IC50 < 0.8 microM), but weak antagonists at NR1A/NR2A receptors (IC50 > 100 microM). In heteromeric NR1A/NR2B receptors, (+) erythro- and (-) threo-ifenprodil (IC50 0.21 and 0.22 microM, respectively) were about 4 times more potent than (-) erythro- and (+) threo-ifenprodil (IC50 0.81 and 0.76, respectively). These results show that the stereoisomers of ifenprodil exhibit a weak though significant stereoselectivity at the NR1A/NR2B NMDA receptor subtype.
Avenet
P
P
Synthélabo Recherche, CNS Research Department, Bagneux, France.
Léonardon
J
J
Besnard
F
F
Graham
D
D
Frost
J
J
Depoortere
H
H
Langer
S Z
SZ
Scatton
B
B
D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D008969:Molecular Sequence Data; D009865:Oocytes; D010880:Piperidines / Q000737:chemistry / Q000494:pharmacology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000145:classification / Q000235:genetics; D013237:Stereoisomerism; D014982:Xenopus laevis
D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; C010739:ifenprodil