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MK‐801 blocks monoamine transporters expressed in HEK cells
Author(s) -
Nishimura Mitsuhiro,
Sato Kohji,
Okada Tomoya,
Schloss Patrick,
Shimada Shoichi,
Tohyama Masaya
Publication year - 1998
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(98)00126-4
Subject(s) - monoamine neurotransmitter , nmda receptor , chemistry , pharmacology , dopamine , serotonin , receptor , dizocilpine , transporter , biology , biochemistry , endocrinology , gene
(+)‐MK‐801 is known to be a specific non‐competitive antagonist of N ‐methyl‐ d ‐aspartate (NMDA) receptors. However, besides having an anticonvulsant effect, this compound possesses a central sympathomimetic effect and an anxiolytic‐like action, raising the possibility that (+)‐MK‐801 might affect monoamine uptake systems. To elucidate this possibility, we investigated the effects of (+)‐MK‐801 on monoamine transporters expressed in HEK cells. (+)‐MK‐801 significantly inhibited the uptake of all three monoamine transporters in a dose‐dependent manner and the inhibitions were competitive with respect to monoamines. The K i values of (+)‐MK‐801 on the norepinephrine, dopamine and serotonin transporters were 3.2 μM, 40 μM and 43 μM, respectively. In addition, (−)‐MK‐801, a less potent antagonist of NMDA receptors, also inhibited monoamine transporters with a similar potency as that of (+)‐MK‐801. These results clearly indicate that MK‐801, a non‐competitive antagonist of NMDA receptors, competitively inhibits monoamine transporters without stereoselectivity.