Dizocilpine blocks NMDA receptors in a use- and voltage-dependent manner, since the channel must open for the drug to bind inside it.

It inhibits the induction of long term potentiation[4] and has been found to impair the acquisition of difficult, but not easy, learning tasks in rats[5][6] and primates.

[7] Because of these effects of dizocilpine, the NMDA receptor pore blocker ketamine is used instead as a dissociative anesthetic in human medical procedures.

While ketamine may also trigger temporary psychosis in certain individuals, its short half-life and lower potency make it a much safer clinical option.

However, dizocilpine is the most frequently used uncompetitive NMDA receptor antagonist in animal models to mimic psychosis for experimental purposes.

Excitatory amino acids, such as glutamate and aspartate, are released in toxic amounts when the brain is deprived of blood and oxygen and NMDA antagonists are thought to prevent the neurodegeneration through the inhibition of these receptors.

[19][20] Behavioural studies have shown that NMDA receptors are involved in the development of psychological dependence caused by chronic administration of morphine.

It is suggested that stimulating NR2B subunits of the NMDA receptor and its associated kinases in the nucleus accumbens leads to the rewarding effect caused by morphine.

Inhibition of this receptor and its kinases in the nucleus accumbens by co-treatment with NMDA antagonists prevents morphine-associated psychological dependence.

[21] An earlier study has shown that the prevention of morphine-associated psychological dependence was not due to state-dependency effects induced by dizocilpine[22] but rather reflect the impairment of learning that is caused by NMDA antagonists.

[28] Dizocilpine was also shown to potentiate the ability of levodopa to ameliorate akinesia and muscular rigidity in a rodent model of parkinsonism.

Dizocilpine had a promising future as a neuroprotective agent until neurotoxic-like effects, called Olney's Lesions, were seen in certain brain regions of lab rats.

[31] Other neurons in the area expressed an abnormal amount of heat shock protein[33] as well as increased glucose metabolism[34] in response to NMDA antagonist exposure.