MK-801 BLOCKS MONOAMINE TRANSPORTERS EXPRESSED IN HEK CELLS

(+)-MK-801 is known to be a specific non-competitive antagonist of N-m ethyl-D-aspartate (NMDA) receptors, However, besides having an anticon vulsant effect, this compound possesses a central sympathomimetic effe ct and an anxiolytic-like action, raising the possibility that (+)-MK- 801 might affect monoamine uptake systems, To elucidate this possibili ty, we investigated the effects of (+)-MK-801 on monoamine transporter s expressed in HEK cells, (+)-MK-801 significantly inhibited the uptak e of all three monoamine transporters in a dose-dependent manner and t he inhibitions were competitive with respect to monoamines, The K-i va lues of (+)-MK-801 on the norepinephrine, dopamine and serotonin trans porters were 3.2 mu M, 40 mu M and 43 mu M, respectively, In addition, (-)-MK-801, a less potent antagonist of NMDA receptors, also inhibite d monoamine transporters with a similar potency as that of (+)MK-801, These results clearly indicate that MK-801, a noncompetitive antagonis t of NMDA receptors, competitively inhibits monoamine transporters wit hout stereoselectivity. (C) 1998 Federation of European Biochemical So cieties.