Tricyclic antidepressants block N‐methyl‐ d ‐aspartic acid‐induced lethality in mice

It has been suggested on the basis of in vitro studies that tricyclic antidepressants interact with the N-methyl-D-aspartic acid (NMDA)-receptor complex to block the action of NMDA. The present study showed that tricyclic antidepressants prevented lethality produced by a large dose of NMDA. The potency of the drugs in preventing NMDA-induced lethality correlated with the inhibition of [3H]-MK-801 binding at the NMDA receptor complex, and not with effects on amine uptake. These in vivo data support the in vitro data of Reynolds & Miller (1988a,b).