MK-801 AND ENANTIOMERS - POTENTIAL ANTIDEPRESSANTS OR FALSE POSITIVESIN CLASSICAL SCREENING MODELS

In the present experiments, the noncompetitive NMDA antagonist 11-dihy droxy-5H-dibenzo(ad)cyclo-hepten-5,10-imine (MK-801) and its (+) and ( -) enantiomers were tested in classical screening models used to detec t potential antidepressants. The drug and its enantiomers were active in the tail suspension test (TST). The racemate was also active in the forced swimming test (FST). The effects in these tests occurred, howe ver, at doses with marked stimulant activity. Further investigations ( reserpine, apomorphine, and yohimbine tests) could not confirm the sus pected antidepressant activity. Other NMDA antagonists-2-amino-7-phosp honoheptanoic acid (AP7), kynurenic acid, and 1-glutamic acid diethyle ster (GDEE)-showed no activity in the TST. These findings throw doubt concerning the potential antidepressant activity of MK-801 and other N MDA antagonists.