Ca2+ antagonists effect an antidepressant-like adaptation of the NMDA receptor complex.
Chronic, but not acute treatment of mice with nimodipine and diltiazem produce significant increases in the IC50 of glycine to inhibit [3H]5,7-dichlorokynurenic acid binding in cerebral cortex. Such adaptive changes in the ligand binding properties of the NMDA receptor complex are also manifested following chronic treatment with antidepressants from every principal therapeutic class. These findings indicate voltage-dependent calcium channel antagonists would be strong candidates for rigorous clinical trials in depressive disorders.
Nowak
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Laboratory of Neuroscience, National Institute on Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0008.
Paul
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IA
Popik
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Young
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Skolnick
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D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001665:Binding Sites; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D003863:Depression / Q000188:drug therapy; D004110:Diltiazem / Q000494:pharmacology; D005998:Glycine / Q000494:pharmacology*; D007736:Kynurenic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D008297:Male; D051379:Mice; D009553:Nimodipine / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism
D000928:Antidepressive Agents; D002121:Calcium Channel Blockers; D016194:Receptors, N-Methyl-D-Aspartate; D009553:Nimodipine; D004110:Diltiazem; D007736:Kynurenic Acid; C066192:5,7-dichlorokynurenic acid; D005998:Glycine