Excitatory amino acids receptor binding

McDonald J. W., Garofalo E. A., Hood T., Sackellares C., Gilman S., McKeever P. E., Troncoso J. C., and Johnston M. V. (1991). Altered excitatory and inhibitory amino acid receptor binding in hippocampus of patients with temporal lobe epilepsy. Ann. Neurol. 29 529-541. 

Both phencyclidine and ketamine bind with high affinity to a number of receptors in the brain, but it is now accepted that the primary target is the sigma-PCP receptor site located in the ion channel of the NMDA excitatory amino acid receptor complex. The precise function of this receptor in the brain is still the subject of debate. It is now known that there are two distinct sigma receptor sites in the mammalian brain (ctj and a2) which are not associated with the NMDA receptor complex. Haloperidol and the atypical neuroleptic remoxipride bind with high affinity to such sites, and it has been postulated that some typical and atypical neuroleptics may owe some of their pharmacological effects to their action on such receptors. 

Ketamine binds to the excitatory amino acid receptor known as theN-methyl-D-aspartate (NMDA) receptor complex, which regulates calcium flow through an ion channel (Figure 4.4). Therefore, ketamine s direct action is to block the movement of calcium through this channel.56... 

Domoic acid (CAS 14277-97-5, C15H21NO6) is produced by Nitzchia pungens. The toxin accumulates in the hepatopancreas of mussels, scallops, and other filter-feeding shellfish. Heat-stable neurotoxic domoic acid is similar in structure to the excitatory dicarboxylic amino acid, kainic acid, and has an antagonistic effect at the glutamate receptor. Domoic acid acts as a potent excitatory neurotransmitter, and it binds to excitatory amino acid receptors in the central nervous system in invertebrates. 

Young, A.B. and Egg, G.E. (1991) Excitatory amino acid receptors in the brain membrane binding and receptor autoradiographic approaches. In D. Lodge and G.L. Collin-gridge (Eds.), Trends in Pharmacological Sciences. The Pharmacology of Excitatory Amino Acids, Special Report, Elsevier, Amsterdam, pp. 18-24. 

L-689,560 is an excitatory amino acid antagonist. It binds to but does not activate excitatory amino acid receptors, thereby blocking the actions of agonists. The drug is a selective antagonist for the glycine site on the A7-methyl-D-aspartate receptor. ... 

The prevalent receptor model for the excitatory amino acid is a tetrameric complex. As mentioned in the text, there is evidence that the channel conductance depends on the number of subunits that bind a ligand. Estimate the EC50 value and Hill coefficient for a dose-response curve assuming that the occupation at each subunit has a Kd value of 1 pi I, an % of 1, and that activation induces a transition to an active state independent of the state of the other subunits ... 

PCP binds with high affinity to sites located in the cortex and limbic structures, resulting in blocking of iV-methyl-D-aspartate (NMDA)-type glutamate receptors see Chapter 12). LSD and other psychedelics do not bind to NMDA receptors. There is evidence that NMDA receptors are involved in ischemic neuronal death caused by high levels of excitatory amino acids as a result, there is interest in PCP analogs that block NMDA receptors but with fewer psychoactive effects. 

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