Orphenadrine citrate is a NMDA receptor antagonist with Ki of 6.0 +/- 0.7 μM, HERG potassium channel blocker.Target: NMDA ReceptorOrphenadrine has been used as an antiparkinsonian, antispastic and analgesic drug. Orphenadrine inhibits [3H]MK-801 binding to the phencyclidine (PCP) binding site of the N-methyl-D-aspartate (NMDA)-receptor in homogenates of postmortem human frontal cortex with a Ki-value of 6.0 +/- 0.7 microM. The NMDA receptor antagonistic effects of orphenadrine were assessed using concentration- and patch-clamp techniques on cultured superior colliculus neurones. Orphenadrine blocked open NMDA receptor channels with fast kinetics and in a strongly voltage-dependent manner. The IC50-value against steady state currents at -70 mV was 16.2 +/- 1.6 microM (n = 6). Orphenadrine exhibited relatively fast, concentration-dependent open channel blocking kinetics (Kon 0.013 +/- 0.002 10(6) M-1S-1) whereas the offset rate was concentration-independent (Koff 0.230 +/- 0.004 S-1) [1]. Orphenadrine competitively inhibited [3H]nisoxetine binding in rat vas deferens membranes (Ki = 1.05+/-0.20 microM). It can be concluded that orphenadrine, at low micromolar concentrations, interacts with the noradrenaline reuptake system inhibiting its functionality and thus potentiating the effect of noradrenaline [2].
ZD-9379 is a potent, orally active, and brain penetrant full antagonist at the glycine site of the NMDA receptor. ZD-9379 has neuroprotective effect[1][2].
CGP 78608 hydrochloride is a highly potent and selective antagonist at the glycine-binding site of the NMDA receptor, with an IC50 of 6 nM. CGP 78608 acts as a potentiator of GluN1/GluN3A-mediated glycine currents, with an estimated EC50 in the low nM range (26.3 nM). Anticonvulsant activity[1][2].
Quisqualic acid (L-Quisqualic acid), a natural analog of glutamate, is a potent and pan two subsets (iGluR and mGluR) of excitatory amino acid (EAA) agonist with an EC50 of 45 nM and a Ki of 10 nM for mGluR1R. Quisqualic acid is isolated from the fruits of Quisqualis chinensis[1][2].
6-Methoxy-2-naphthoic acid is an NMDA receptor modulator extracted from patent WO 2012019106 A2.
Gavestinel (GV 150526) is a potent, selective, orally active and non-competitive antagonist of NMDA receptor. Gavestinel binds to the glycine site of the NMDA receptor, with a pKi of 8.5. Gavestinel can be used for the research of acute ischemic stroke[1].
Farampator-d10 (CX-691-d10) is the deuterium labeled Farampator. Farampator (CX-691) is an AMPA receptor positive modulator.
UBP301 is a potent and selective antagonist of kainate receptor with IC50 and KD of 164 μM and 5.94 μM, respectively. UBP301 has ∼30-fold selectivity of kainate receptor over AMPA receptor. UBP301 is the derivative of willardiine[1].
Orphenadrine-d3 (hydrochloride) is the deuterium labeled Orphenadrine hydrochloride[1]. Orphenadrine hydrochloride is an orally active and non-competitive NMDA receptor antagonist (crosses the blood-brain barrier) with a Ki of 6.0 μM. Orphenadrine hydrochloride relieves stiffness, pain and discomfort due to muscle strains, sprains or other injuries. Orphenadrine hydrochloride is also used to relieve tremors associated with parkinson's disease. Orphenadrine citrate has good neuroprotective properties, can be used in studies of neurodegenerative diseases[2][3].
Dynorphin A (1-10) an endogenous opioid neuropeptide, binds to extracellular loop 2 of the κ-opioid receptor. Dynorphin A (1-10) also blocks NMDA-activated current with an IC50 of 42.0 μM.
Felbamate hydrate (FBM) is a potent nonsedative anticonvulsant whose clinical effect may be related to the inhibition of N-methyl-D-aspartate (NMDA) .Target: NMDA ReceptorFelbamate (marketed under the brand name Felbatol by MedPointe) is an anti-epileptic drug used in the treatment of epilepsy. It is used to treat partial seizures (with and without generalization) in adults and partial and generalized seizures associated with Lennox-Gastaut syndrome in children. However, an increased risk of potentially fatal aplastic anemia and/or liver failure limit the drugs usage to severe refractory epilepsy.Felbamate has been proposed to a unique dual mechanism of action as a positive modulator of GABAA receptors and as a blocker of NMDA receptors, particularly isoforms containing the NR2B subunit. Although it is clear that felbamate does cause pharmacological inhibition of NMDA receptor of relevance of NMDA receptor blockade as a strategy for the treatment of human epilepsy has been questioned. Therefore, the importance of the effects of felbamate on NMDA receptors to its therapeutic action in epilepsy is uncertain.
NMDA receptor modulator 5 (Compound 195) is a potent NMDA receptor modulator. NMDA receptor modulator 5 can be used for neurological disorder research[1].
TCN 213 is a selective, surmountable, glycine-dependentlly GluN1/GluN2A NMDAR antagonist with IC50s of 0.55, 3.5, 40 μM in the presence of 75, 750, 7500 nM glycine, respectively. TCN 213 can be used to monitor, pharmacologically, the switch in NMDAR expression in developing cortical neurones[1][2].
MRZ 2-514 is an antagonist of the strychnine-insensitive modulatory site of the NMDA receptor (glycineB), with Ki of 33 μM.
NMDA receptor modulator 4 (Compound 169) is a potent NMDA receptor modulator. NMDA receptor modulator 4 can be used for neurological disorder research[1].
BPAM344 is a kainate receptor (KAR) subunits GluK1b, GluK2a, and GluK3a positive allosteric modulator (PAM)[1].
TCN 201 is a potent, selective and non-competitive antagonist of GluN1/GluN2A NMDAR. TCN 201 antagonism is dependent on the GluN1-agonist concentration. TCN 201 allows pharmacological identification of native GluN2A-containing NMDAR populations[1].
Ro 25-6981 hydrochloride is a potent, selective and activity-dependent NR2B subunit specific NMDA receptor antagonist. Ro 25-6981 hydrochloride shows anticonvulsant and anti-parkinsonian activity. Ro 25-6981 hydrochloride has the potential for the research of parkinson's disease (PD)[1][2][3].
CX546 is a selective positive AMPAR modulator; the prototypical ampakine agent.IC50 value:Target: AMPAR agonistin vitro: Treatments with the ampakine CX614 markedly and reversibly increased brain-derived neurotrophic factor (BDNF) mRNA and protein levels in cultured rat entorhinal/hippocampal slices [1]. in contrast to cyclothiazide or IDRA 21, the Ampakine CX546 binds specifically to the agonist bound nondesensitized receptor, most likely acting by destabilizing the desensitized receptor conformation [2]. In binding tests, CX546 caused an approximately 2-fold increase in the affinity for radiolabeled agonists, whereas CX516 was ineffective [3]. in vivo: Intraperitoneal injections of CX546 increased hippocampal BDNF mRNA levels in aged rats and middle-aged mice [1]. Administration of the positive modulator of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors (AMPAR), CX546, during the conditioning phase only, improved the disrupted LI in mGluR5 knockout mice and facilitated LI in control C57BL/6J mice, given extended number of conditioning trails (four conditioning stimulus-unconditioned stimulus) [4].
UBP608 is a potent N-Methyl-D-aspartate receptors (NMDARs) negative allosteric modulator. UBP608 has the potential for the research of neurological disorders[1].
Meclofenoxate hydrochloride, an ester of dimethylethanolamine (DMAE) and 4-chlorophenoxyacetic acid (pCPA), has been shown to improve memory, have a mentally stimulating effect, and improve general cognition.IC50 value: Target: nootropicMeclofenoxate, administered in a dose of 50 mg/kg twice daily for 7 days using the maze-training method, increased the number of responses to the conditioned stimulus, when retention tests were made 24 hours and 7 days after training, whereas citicholine, applied in the same way in a dose of 10 mg/kg, shortened the latency of the responses with reinforcement during the training and increased the number of correct responses to the conditioned stimulus in retention tests 7 days after the training [1]. Meclofenoxate appears to increase the consolidation of new information into long-term memory, but does not affect other aspects of remembering [2].
(RS)-AMPA ((±)-AMPA) monohydrate is a glutamate analogue and a potent and selective excitatory neurotransmitter L-glutamic acid agonist. (RS)-AMPA monohydrate does not interfere with binding sites for kainic acid or NMDA receptors[1][2].
Eliprodil(SL-820715) is a non-competitive NR2B-NMDA receptor antagonist(IC50=1 uM), less potent for NR2A- and NR2C-containing receptors(IC50> 100 uM).IC50 value:Target: NR2B-NMDA antagonistHuman N-type Ca2+ channel currents were inhibited by ifenprodil and eliprodil with IC50 values of 50 microM and 10 microM respectively whereas P-type Ca2+ channel currents were inhibited reversibly by ifenprodil and eliprodil with approximate IC50 values of 60 microM and 9 microM respectively. eliprodil (1 microm) produced a moderate reverse rate-dependent prolongation of the action potential duration (7.4+/-1.5, 8.9+/-2.1 and 9.9+/-1.8% at cycle lengths of 300, 1000 and 5000 ms, respectively; n=9).
(S)-(-)-5-Fluorowillardiine Hcl is a potent and specific AMPAR agonist.
JAMI1001A is a positive allosteric modulator of AMPA receptor. JAMI1001A efficaciously modulates AMPA receptor deactivation and desensitization of both flip and flop receptor isoforms[1].
DQP-26 is a potent NMDAR negative allosteric modulator with IC50 values of 0.77 μM and 0.44 μM for GluN2C and GluN2D, respectively. DQP-26 has the potential for NMDAR-associated neurological disease research[1].
(RS)-(Tetrazol-5-yl)glycine (D,L-(tetrazol-5-yl)glycine) is a highly potent and selective N-methyl-D-aspartate (NMDA) receptor agonist[1]. (RS)-(Tetrazol-5-yl)glycine has EC50s of 99 nM, 1.7 μM for GluN1/GluN2D and GluN1/GluN2A, respectively[2]. (RS)-(Tetrazol-5-yl)glycine induces seizure responses and Fos in mice[3].
CMPDA is a positive allosteric modulator of AMPA receptors with EC50s of 45.4 ± 4.2 nM/63.4 ± 5.6 nM for GluA2i/GluA2o receptor.IC50 value: 45.4 ± 4.2 nM/63.4 ± 5.6 nM(GluA2i/GluA2o) [1]Target: AMPAR modulatorCMPDA was nearly equipotent at modulating the two isoforms of GluA2 receptors, whereas CMPDB displayed a modest preference for the flip splice variant. Similar to CX614, CMPDA slowed the rate of deactivation of GluA2o receptors approximately 2-fold but had no effect on GluA2i receptor deactivation [1].
Memantine, an amantadine derivative with low to moderate-affinity for NMDA receptors, inhibit CYP2B6 and CYP2D6 with Ki of 0.51 nM and 94.9 μM, respectively..Target: NMDA Receptor, Memantine (Ebixa, Axura, Namenda, Akatinol) is a moderate-affinity, uncompetitive, voltage-dependent, NMDA-receptor antagonist with fast on/off kinetics that inhibits excessive calcium influx induced by chronic overstimulation of the NMDA receptor. Memantine is approved in the US and the EU for the treatment of patients with moderate to severe dementia of the Alzheimer's type [1]. Memantine has considerable therapeutic potential for the myriad of clinical entities associated with NMDA receptor-mediated neurotoxicity [2]. Memantine blocked 200 microM NMDA-evoked responses with a 50% inhibition constant (IC50) of approximately 1 microM at -60 mV and an empirical Hill coefficient of approximately 1 [3].
(RS)-AMPA ((±)-AMPA) hydrobromide is a glutamate analogue and a potent and selective excitatory neurotransmitter L-glutamic acid agonist. (RS)-AMPA hydrobromide does not interfere with binding sites for kainic acid or NMDA receptors[1][2].