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.
Lancaster
J M
JM
Department of Pharmacology and Therapeutics, University of Wales College of Medicine, Heath Park, Cardiff, UK.
Davies
J A
JA
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000503:physiopathology; D003292:Convulsants / Q000494:pharmacology; D003337:Corpus Callosum / Q000187:drug effects / Q000503:physiopathology; D003891:Desipramine / Q000494:pharmacology*; D004827:Epilepsy / Q000235:genetics / Q000503:physiopathology*; D005260:Female; D007473:Ion Channels / Q000187:drug effects; D007649:Ketamine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA / Q000502:physiology; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D017981:Receptors, Neurotransmitter / Q000187:drug effects* / Q000502:physiology; D017478:Receptors, Phencyclidine; D013268:Stimulation, Chemical
D000927:Anticonvulsants; D003292:Convulsants; D007473:Ion Channels; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D017478:Receptors, Phencyclidine; D016202:N-Methylaspartate; D007649:Ketamine; D008274:Magnesium; D003891:Desipramine