Pharmacological profile of dizocilpine (MK-801) and its potential use in animal model of schizophrenia
Abstract
N-Methyl-D-aspartate (NMDA) receptor belongs to the group of glutamate receptors, which are further divided into ionotropic and metabotropic. It affects synaptic plasticity and the development of neuronal synapsis in CNS.
Ionotropic NMDA receptors are activated by glutamate, thereby flowing positively charged ions through the membrane along its concentration gradient. However, glutamate overload leads to excitotoxicity, due to high levels of Ca2+, which leads to cell death assocciated with neurodegenerative diseases.
NMDA antagonists like dizocilpine reduce intracellular concentration of Ca2+ by modulating permeability of NMDA receptor channel. Dizocilpine act as a non-competitive NMDA receptor antagonist with anticonvulsant and anesthetic properties.
Its therapeutic use in humans is limited due its numerous side effects, but it is experimentally used as an animal model of schizophrenia.