Antidepressant-like actions of the polyamine site NMDA antagonist, eliprodil (SL-82.0715).
Functional N-methyl-D-aspartate (NMDA) antagonists including competitive antagonists, glycine partial agonists, and use-dependent channel blockers 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 produced a dose-dependent reduction in immobility in the forced swim test, but was inactive in the tail suspension test. Chronic treatment with eliprodil produced both a significant downregulation of beta-adrenoceptors and a reduction in the potency of glycine to inhibit [3H]5,7-dichlorokynurenic 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.
Laboratory of Neuroscience, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
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D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D015317:Biogenic Polyamines / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005998:Glycine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D007099:Imipramine / Q000494:pharmacology; D007736:Kynurenic Acid / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology*; D018009:Receptors, Glycine / Q000037:antagonists & inhibitors
D018759:Adrenergic Uptake Inhibitors; D000319:Adrenergic beta-Antagonists; D000928:Antidepressive Agents; D015317:Biogenic Polyamines; D018691:Excitatory Amino Acid Antagonists; D010880:Piperidines; D018009:Receptors, Glycine; D007736:Kynurenic Acid; D007099:Imipramine; C066192:5,7-dichlorokynurenic acid; D005998:Glycine; C058083:eliprodil