Changes in preference for receptor subtypes of configurational variants of a glutamate analog: conversion from the NMDA-type to the non-NMDA type.
The (2S,3R,4S) isomer of 2-(carboxycyclopropyl)glycines (CCG) (L-CCG-IV) is a potent NMDA-type agonist in the mammalian central nervous system. L-CCG-IV is a conformationally restricted glutamate analogue in which the cyclopropyl group fixes the glutamate chain, and closely mimics the folded conformation of L-glutamate. (6R)-Substituted L-CCG-IV, however, demonstrated pharmacological properties of non-NMDA type agonists in the newborn rat spinal motoneuron while (6S)-CCG derivatives showed similar properties to the parent compound, L-CCG-IV. In the dorsal root fiber of newborn rats, (6R)-methoxymethyl and benzyloxymethyl substituted L-CCG-IV caused kainate-like depolarization. The depolarizing potency of (6R)-benzyloxymethyl substituted L-CCG-IV was slightly lower than that of kainate, demonstrating a relatively high potency.
Ishida
M
M
Tokyo Metropolitan Institute of Medical Science, Japan.
Ohfune
Y
Y
Shimada
Y
Y
Shimamoto
K
K
Shinozaki
H
H
D000600:Amino Acids, Dicarboxylic / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D005071:Evoked Potentials / Q000187:drug effects; D005971:Glutamates / Q000494:pharmacology*; D066298:In Vitro Techniques; D007536:Isomerism; D007608:Kainic Acid / Q000494:pharmacology; D008968:Molecular Conformation; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D013329:Structure-Activity Relationship
D000600:Amino Acids, Dicarboxylic; D005971:Glutamates; D007608:Kainic Acid; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; C035261:(alpha-carboxycyclopropyl)glycine