Clinical Physiology and Mechanism of Dizocilpine (MK‐801): Electron Transfer, Radicals, Redox Metabolites and Bioactivity

Dizocilpine (MK-801), a drug with anticonvulsant and anesthetic properties, forms oxidative metabolites like hydroxylamines and phenolics. These metabolites may participate in redox reactions involving electron transfer and radical formation, similar to cocaine metabolism. The drug acts as an antagonist of the N-methyl-D-aspartate (NMDA) receptor in the glutamate category, which is linked to its central nervous system effects. Administration of dizocilpine induces learning impairment and behavioral deficits in mice, and it also influences fear and exerts analgesic effects in pain control. The review covers recent literature on MK-801/NMDA receptor involvement in various bioactivities.

Study at a glance

Abstract

Dizocilpine (MK‐801), an extensively investigated drug possessing secondary amine and benzenoid functions, displays a wide array of biological properties, including anticonvulsant and anesthetic. There is scant discussion of biomechanism. A relevant, important finding is formation of oxidative metabolites in the hydroxylamine and phenolic categories. Analogy to cocaine metabolites suggests participation of redox entities, such as, hydroxylamine, nitroxide and nitrosonium, which can lead to electron transfer and radical formation. There is also similarity to metabolism by 3,3′‐iminodipropionitrile and phencyclidine. Alternatively, the phenolic metabolites are well‐known precursors of ET quinones. The review documents various physiological effects, mainly involving the central nervous system. Also of interest are the pro‐ and anti‐oxidant properties. Considerable attention has been paid to MK‐801 as an antagonist of the N‐methyl‐D‐aspartate receptor in the glutamate category. This aspect is often associated with effects on the central nervous system. The review also provides recent literature dealing with MK‐801/NMDA receptor in various areas of bioactivity. Studies were made of MK‐801 involvement in working memory processing. Deficits in behavior were noted after administration of the drug. Treatment of mice with dizocilpine induced learning impairment. The influence of MK‐801 on fear has been investigated. The substance is known to exert an analgesic effect in pain control. A number of reports deal with anesthetic properties.