Discovered by a team at Merck in 1982, (+)-dizocilpine (MK-801) is an uncompetitive NMDA receptor antagonist that enters and plugs the ion channel pore only after glutamate and glycine have opened the channel ("use-dependent" block).
Because MK-801 blocks Ca²⁺ influx through synaptic NMDA receptors, it abolishes hippocampal long-term potentiation (LTP) and is widely used in preclinical neuroscience to model NMDA-hypofunction cognitive and psychotic-spectrum deficits.
Although initially investigated as an anticonvulsant and neuroprotectant in ischemic stroke, MK-801 was restricted to laboratory research after John Olney showed in 1989 that high doses cause vacuolar neuronal lesions (Olney's lesions) in rat posterior cingulate cortex.