Enantiomeric propanolamines have been identified as a new class of NR2B-selective NMDA receptor antagonists. The most effective agents are biaryl structures, synthesized in six steps with overall yields ranging from 11-64%. The compounds are potent and selective inhibitors of NR2B-containing recombinant NMDA receptors with IC 50 values between 30-100 nM. Potency is strongly controlled by substi...

Several pharmacologically distinct sites are known to modulate the N-methyl-D-aspartate (NMDA) receptor/ion complex, including a site within the ion channel which binds uncompetitive antagonists like phencyclidine (PCP) or dizocilpine. Glycine acts as a co-agonist for activation of the NMDA receptor complex through a strychnine-insensitive receptor, which is a potential target for novel therape...

Pain is detected by two different types of peripheral nociceptor neurons, C-fiber nociceptors with slowly conducting unmyelinated axons, and A-delta nociceptors with thinly myelinated axons. During inflammation, nociceptors become sensitized, discharge spontaneously, and produce ongoing pain. Prolonged firing of C-fiber nociceptors causes release of glutamate which acts on N-methyl-D-aspartate ...

Multiple studies demonstrate that coadministration of N-methyl-D-aspartate (NMDA) receptor antagonists with the opioid agonist morphine attenuates the development of analgesic tolerance. Sex differences in the effects of noncompetitive, but not competitive NMDA receptor antagonists on acute morphine analgesia, have been reported in mice, yet the role of sex in modulation of morphine tolerance b...

The effect of serotonin (5-HT) receptor blockade on rhythmic network activity and on N-methyl--aspartate (NMDA) receptor-induced membrane voltage oscillations was examined using an in vitro neonatal rat spinal cord preparation. Pharmacologically induced rhythmic hindlimb activity, monitored via flexor and extensor electroneurograms or ventral root recordings, was abolished by 5-HT receptor anta...

introduction: it has been shown that administration of win55,212-2, a cannabinoid receptor agonist, into the basolateral amygdala (bla), dose-dependently increases the thermal latency to withdrawal in the tail-.ick test and decreases pain related behaviors in both phases of the formalin test. recent human and animal imaging data suggest that the nucleus accumbens (nac) is an important neural su...

Clinical reports have described a long-lasting relief in neuropathic pain patients treated with NMDA receptor antagonists; it is unclear, however, what mediates this effect. In this work, we have used two NMDA antagonists of different class to investigate if the antiallodynic effects in a rat neuropathy model can outlast their in vivo NMDA antagonism. Both the uncompetitive NMDA antagonist keta...

Newly synthesized Arc mRNA is selectively targeted to synapses that have experienced particular patterns of activity. Here, we demonstrate that the targeting requires NMDA receptor activation. Arc expression was induced by an electroconvulsive seizure, and the newly synthesized mRNA was then targeted to synaptic sites by activating the perforant path projections to the dentate gyrus. When micro...

Successful management of epilepsy still remains a vital problem. Despite using various combinations of antiepileptic drugs (AEDs), 20-25% of epileptic patients are insensitive to currently available medication. Therefore, there is a considerable need for finding a more effective AED or synergistic combinations of AEDs. Experimental and clinical data indicate that excitatory amino acid (EAA) rec...

BACKGROUND The purpose of this study was to determine how the activation of different regulatory domains of the NMDA complex affects the antianxiety effect of antagonists acting at its distinct binding sites. METHODS The anxiolytic-like activity was assessed by the elevated plus-maze test in mice. RESULTS The anxiolytic activity of CGP 37849 (a competitive NMDA receptor antagonist) and L-70...