Abstract
NMDA receptors are widely distributed, rapidly responding ligand-gated and voltage-dependent cationic channels sensitive to L-glutamate and glycine. The NMDA receptors are essential for the normal function of the excitatory glutamatergic neurotransmission.
The receptor/channel complexes are highly permeable to Ca2+ and are subject to regulation by a variety of factors. Usually present as tetramers of protein subunits, NMDA receptors are formed by NR1, NR2 and/or NR3 subunits; however, all functional complexes must include NR1 subunits.
The presence of NR2 and NR3 subunits and/or the nature of their spice variants may influence a range of NMDA receptor characteristics such as binding affinities for glutamate and glycine. Altered function of NMDA receptors has been linked to the etilogy of mental disease, particularly as a part of the "glutmatergic hypothesis of schizophrenia".
The functional changes in NMDA receptors could result from genetically determined variations in individual protein subunits or from their abnormal expression. In addition, NMDA receptors can mediate perinatal neurotoxic insults such as those postulated in the "developmental hypothesis of schizophrenia".
D-Serine is another endogenous co-agonist at NMDA receptors and recent evidence suggests that disturbances in D-Serine homeostasis may also contribute to mechanisms of schizophrenia. Putative involvement of NMDA receptors in schizophrenia, their crucial role in the normal brain function and the complex but extensively studied nature of their regulation makes NMDA receptors promising targets for drugs.
Additional investigations using either animal models or combination of genetic studies and imaging technique in human patients in vivo would greatly aid the development of novel classes of neuroleptics.