NMDA receptors anesthetics

The ion-channel blocking mechanism has been widely tested and found to be important in both pharmacology and physiology. Examples are the block of nerve and cardiac sodium channels by local anesthetics, or block of NMDA receptor channels by Mg2+ and the anesthetic ketamine. The channel-block mechanism was first used quantitatively to describe block of the squid axon K+ current by tetraethylammonium (TEA) ions. The effects of channel blockers on synaptic potentials and synaptic currents were investigated, particularly at the neuromuscular junction, and the development of the single-channel recording technique allowed channel blockages to be observed directly for the first time. 

Hypofunction of NMDA receptors may contribute to the endophenotype of schizophrenia. The hypothesis that hypofunction of a subpopulation of NMDA receptors contributes to the pathophysiology of schizophrenia has gained considerable support over the last decade (see Fig. 54-1). The dissociative anesthetics including phencyclidine (PCP) and ketamine when introduced clinically 40 years ago were noted to produce a syndrome that was difficult to distinguish from schizophrenia. These agents act as noncompetitive open-channel blockers of the NMDA receptor. 

A few ongoing studies involving chloroform have been identified. The effects of volatile anesthetics on the N-methyl-D-aspartate (NMDA) receptor-channel complex are being studied. Specific aims are to... 

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. 

DISSOCIATIVE ANESTHETIC An anesthetic that produces an unresponsive state by chemically muting the ability of N-methyl-D-aspartate (NMDA) receptors in the brain to process signals. 

NMDA RECEPTOR ANTAGONIST A class of anesthetics that block particular neurotransmitters located in the brain s cerebral cortex and hippocampus—regions responsible for memory, language, and motor control. 

Finally, there was a resurgence of interest in psychotogenic effects of ketamine in the early 1990s, following demonstrations that dissociative anesthetics such as PCP and ketamine induce their unique psychotomimetic effects by binding to a site located within the ion pore of the NMDA receptor (Anis et al., 1983 Javitt et al., 1987 Javitt and Zukin, 1991). Such studies remain ongoing and provide... 

No effective treatment is known. Drugs that counteract the effect of glycine on neuronal cells, such as strychnine, diazepam, and dextromethorphan, could bring mild benefits in milder forms of the condition. Ketamine, an anesthetic blocker of the N-methyl-n-aspartate (NMDA) receptor channel, brought a partial improvement of neurological symptoms and EEG findings m some patients, but their developmental milestones were delayed. 

---