NMDA receptors noncompetitive antagonists

Antagonists selective for kainate receptors are not available yet. The non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) blocks AMPA as well as kainate receptors. Nevertheless, compounds like GYKI53655, which acts as a noncompetitive antagonist of AMPA receptors and completely blocks AMPA receptor function at certain concentrations at which no antagonistic effect on kainate receptors is discernible, has been used to demonstrate the kainate receptor-mediated currents in neurons. 

Hanania, T. and Zahniser, N.R., Locomotor activity induced by noncompetitive NMDA receptor antagonists versus dopamine transporter inhibitors opposite strain differences in inbred long-sleep and short-sleep mice, Alcohol Clin. Exp. Res., 26, 431, 2002. 

Ida I., Aami T., Kuribara H. Inhibition of cocaine sensitization by MK-801 a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist evaluation by ambulatory activity in mice. Jpn. J. Pharmacol. 69 83, 1995. 

Glutamate systems have long been implicated in the pathophysiology of schizophrenia. Strong if circumstantial evidence comes from the psychosis associated with phencyclidine (PGP) administration PGP blocks of the ion channel the glutamate/NMDA receptor. Psychosis due to PGP and other noncompetitive NMDA antagonists includes the development of negative as well as positive symptoms and therefore is considered a better model of schizophre-... 

Tzschentke T. M. and Schmidt, W. J. Does the noncompetitive NMDA receptor antagonist dizocilpine (MK801) really block behavioural sensitization associated with repeated drug administration , Trends Pharmacol. Sci. 1998, 19, 447-451. 

Another member of the arylcyclohexylamine structural class is ketamine, which is a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, meaning it disables certain higher-function signaling mechanisms in the brain (consciousness, memory, perception, and motor activity) from lower functions (breathing and heart rate). Ketamine is manufactured commercially for use as a surgical anesthetic for both humans and animals. 

Ketamine and PCP are use-dependent noncompetitive antagonists of the NMDA receptor that bind to the intrachannel site of the receptor and prevent calcium ion flux (Javitt and Zukin, 1991) in humans they cause a syndrome that is clinically indistinguishable from schizophrenia and that involves not only positive (psychotic) symptoms, but also, negative symptoms (blunted affect, avolition), thought... 

One of the most popular hypotheses to explain schizophrenia, the glutamate hypothesis of schizophrenia, is based on the observation of psychotomimetic effects of noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists, such as phencyclidine (PCP), dizocilpine (MK-801), and ketamine. Like amphetamine, NMDA antagonists produce a psychosis-like state when administered to healthy individuals. Further... 

Ketamine acts as a noncompetitive antagonist of NMDA receptors. It induces changes of perception, memory, and cognition throughout the brain. Drugs like ketamine are said to work globally, meaning that they directly or indirectly... 

Is a low to moderate affinity noncompetitive (open-channel) NMDA receptor antagonist, which binds preferentially to the NMDA receptor-operated cation channels... 

Hs Weak noncompetitive NMDA-receptor antagonist (high doses), which may contribute to actions in chronic pain... 

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