Changes in preference for receptor subtypes of configurational variants of a glutamate analog: conversion from the...

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.