Desmethylimipramine potentiates NMDA responses in a mouse cortical slice preparation.

Desmethylimipramine (DMI) has been shown to interact with the N-methyl-D-aspartate (NMDA) receptor complex. Its probable action is through blockade of the cationic channel at the phencyclidine site and as a result it has potential anticonvulsant action. In this present study we have investigated the effects of DMI and ketamine on both NMDA-induced and spontaneous depolarizing shifts in cortical wedges prepared from genetically epilepsy-prone mice (DBA/2). Contrary to published reports, DMI potentiated the effects of NMDA and increased the frequency of spontaneous depolarizations. The actions of ketamine were inhibitory and these were reversed by DMI. Presynaptic mechanisms may be involved in the DMI-induced potentiation and this may explain the lowering of convulsive thresholds seen clinically with tricyclic antidepressants.