Abstract
(1S,3R)-1-Aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) and (1R,3S)-1-aminocyclopentane-1,3-dicarboxylic acid (1R,3S-ACPD) were characterized for potency, efficacy, and selectivity at metabotropic amino acid receptors. 1S,3R-ACPD stimulated [ 3H]phosphoinositide hydrolysis in slices of the neonatal and adult rat hippocampus with full efficacy and twice the potency relative to what has been shown for (±)-trans-ACPD. 1S,3R-ACPD was up to 30 times more potent in activating metamotropic excitatory amino acid receptors, compared to its affinity for [ 3H]CGS19755 binding to NMDA receptors. In contrast, 1R,3S-ACPD was much less potent, efficacious, and selective than 1S,3R-ACPD. Although 1S,3R-ACPD is not specific, it is a most selective and efficacious agonist at metabotropic excitatory amino acid receptors.
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