AbstractMK‐801 is a potent inhibitor of the NMDA subtype of glutamate receptors. Single‐channel and macroscopic current indicate that MK‐801 also inhibits nicotinic acetylcholine receptors (nAChRs). MK‐801 does not significantly increase desensitization of the nAChR, the main action of MK‐801 is to enter and block the open channel. The voltage dependence for block is consistent with a single binding site within the channel that is 50% of the way through the membrane field. The IC50 for block is 3 μM at‐70 mV for currents induced by 0.5 μ;M ACh. The data from both single‐channel and macroscopic currents can be used to estimate a Kd (0) of 7 μM, which is about 40 times higher than the Kd(0) for MK‐801 binding to the NMDA receptor. The relative potency of tricyclic compounds like MK‐801 for various neurotransmitter systems points out that the pharmacologic action of these drugs could involve complicated interactions in vivo.