Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.16.2 (PCP)
 3,761 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glutamate receptor antagonists with selective action at the N-methyl-D-aspartate (NMDA) receptor are promising agents for the neuroprotective and symptomatic pharmacotherapy of various neuropsychiatric disorders. Although NMDA receptor antagonists of the phencyclidine (PCP) type are precluded from clinical use because of their psychotomimetic properties, amantadine and memantine have been administered to human patients with idiopathic Parkinson's disease and spasticity for many years without serious adverse effects. The mechanisms underlying these differences in psychotogenicity of different NMDA receptor antagonist are currently being discussed. Different affinity to the PCP binding site of the NMDA receptor, region-specific pharmacology, as well as different binding profiles to neurotransmitter receptors other than the NMDA type glutamate receptor, most likely play a role in determining whether an NMDA receptor antagonist drug will be tolerated clinically or not.
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PMID:[New therapeutic possibilities with low-affinity NMDA receptor antagonists]. 867 93

Glutamate receptor-dependent neural plasticity is thought to be implicated in memory processes. Ionotropic N-methyl-D-aspartate- (NMDA) sensitive and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate- (AMPA) sensitive glutamate receptors have been particularly studied for their role in synaptic plasticity. Drugs can alter AMPA and NMDA receptor neurotransmission by competing for the glutamate site or other sites on these receptor proteins. Variants of the protein subunits forming AMPA and NMDA heteromers contribute to the complexity of pharmacological activity at these receptors. The NMDA receptor has numerous modulatory centers, including the glycine binding site, NR2B protein specific binding site, and an intrachannel (PCP) binding site. In this study, the accuracy and rate of rats performing under a Fixed Consecutive Number (FCN) operant task were measured after administrations of site-selective AMPA and NMDA receptor modulators. Test compounds included two glycine site NMDA agonists [(+)HA 966 and D-cycloserine], two NR2-B site NMDA antagonists (eliprodil and ifenprodil), an NMDA channel blocking antagonist (MK 801), and a competitively acting AMPA receptor antagonist (NBQX). The accuracy of FCN performance was not affected by response-rate-altering doses of (+) HA 966, D-cycloserine, eliprodil, ifenprodil, or NBQX. MK 801, on the other hand, reduced performance accuracy at several doses. These results are consistent with earlier studies suggesting that AMPA antagonists minimally affect working memory and that glycine and NR2B protein-specific modulatory sites may have advantages as targets for the development of medications intended to alter NMDA receptor-mediated transmission.
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PMID:Site-selective N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate antagonists produce distinct effects in rats performing complex discriminations. 1243 22