Inhibition of N-methyl-D-aspartate activated ion current by desmethylimipramine.
The tricyclic antidepressant desmethylimipramine (DMI) interacts with the NMDA receptor/ionophore complex; however, the site of the interaction has not been clearly established.  Although evidence from receptor binding assays suggests that DMI interacts with the Zn2+ binding site, other binding studies and electrophysiological studies suggest otherwise. Using the whole-cell patch clamp technique to record from cultured hippocampal neurons, we report that recovery of NMDA-activated current from block by DMI is time-dependent and this time-dependent component was not observed following preexposure of neurons to Zn2+. These observations favor the hypothesis that DMI interacts at a binding site within the NMDA receptor/complex channel pore and not at the Zn2+ binding site.
White
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G
Section of Electrophysiology, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD 20852.
Lovinger
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DM
Peoples
R W
RW
Weight
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D000818:Animals; D003891:Desipramine / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D016202:N-Methylaspartate / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects; D051381:Rats; D015032:Zinc / Q000494:pharmacology
D007473:Ion Channels; D016202:N-Methylaspartate; D015032:Zinc; D003891:Desipramine