ANTIDEPRESSANT-LIKE ACTIONS OF THE POLYAMINE SITE NMDA ANTAGONIST, ELIPRODIL (SL-82.0715)

Functional N-methyl-D-aspartate (NMDA) antagonists including competiti ve antagonists, glycine partial agonists, and use-dependent channel bl ockers exhibit antidepressant-like actions in preclinical models. The present study examined the effects of eliprodil (SL-82.0715), an NMDA antagonist acting at polyamine sites, in behavioral and neurochemical tests predictive of antidepressant activity. In mice, eliprodil produc ed a dose-dependent reduction in immobility in the forced swim test, b ut was inactive in the tail suspension test. Chronic treatment with el iprodil produced both a significant downregulation of beta-adrenocepto rs and a reduction in the potency of glycine to inhibit [H-3]5,7-dichl orokynurenic acid binding to strychnine-insensitive glycine receptors in neocortical membranes. In toto, these data indicate that like other NMDA antagonists, eliprodil possesses antidepressant-like actions in preclinical tests predictive of clinical efficacy.