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MK‐801 inhibition of nicotinic acetylcholine receptor channels
Author(s) -
Amador Mariano,
Dani John A.
Publication year - 1991
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.890070305
Subject(s) - nicotinic acetylcholine receptor , nicotinic agonist , acetylcholine receptor , chemistry , alpha 4 beta 2 nicotinic receptor , acetylcholine , pharmacology , ganglion type nicotinic receptor , muscarinic acetylcholine receptor m5 , neuroscience , receptor , muscarinic acetylcholine receptor m3 , biology , biochemistry
MK‐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 IC 50 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 K d (0) of 7 μM, which is about 40 times higher than the K d (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.