nmda-in-2

NMDA-IN-2 (compound 6b) is a Procaine derivative that is an inhibitor of NMDA receptor 2B subtype [1].

3-MATIDA is an effective mGluR-1 antagonist (IC50: 6.3 μM, rat mGluR-1a). Displays ≥ 40-fold selectivity over other receptors: mGluR-5, mGluR-2, mGluR-4 (mGluR-4a) (IC50 > 300 μM), NMDA and GluR (AMPA) (IC50 = 250 μM). 3-MATIDA act as a neuroprotectant in cultured murine cortical cells and rat hippocampal slice cultures in vitro.

1. Linalool (Linalol), a natural compound of the essential oils, has been shown to have antinociceptive, antimicrobial, and anti-inflammatory properties. 2. Linalool was protected against LPS/GalN-induced liver injury through induction of antioxidant defense via Nrf2 activating and reduction inflammatory response via NF-κB inhibition. 3. Linalool biosynthesis and accumulation might be involved in plant defense against bacterial and fungal pathogens and be associated with field resistance to citrus canker. 4. Linalool significantly increased the expression of antioxidant enzymes regulated by Nrf-2 and diminished lung tissue levels of several pro-inflammatory cytokines, including tumor necrosis factor α (TNF-α) and interleukin (IL)-6.

1. Methyl eugenol (4-allylveratrole) is a natural constituent of the essential oils of a number of plants widely used in foodstuffs as flavouring agents, in view of the carcinogenic potential of ME, the need to check its presence in food products with effective analytical methods. 2. Methyleugenol has insecticidal properties. 3. Methyleugenol can inhibit the production of nitric oxide and decreased the protein expression of inducible nitric oxide synthase, it down-regulates the production of pro-inflammatory cytokines in the ischemic brain as well as in immunostimulated mixed glial cells; indicates that methyleugenol could be useful for the treatment of ischemia/inflammation-related diseases. 4. Methyleugenol has cytotoxicity and genotoxicity. 5. Intravenous (i.v.) treatment with methyleugenol (ME) in either anesthetized or conscious rats elicits hypotension, an effect that seems related to an active vascular relaxation rather than withdrawal of sympathetic tone. 6. Methyleugenol has antinociceptive effect on the second phase of formalin-induced pain, may be due to the inhibition of N-methyl-d-aspartic acid (NMDA) receptor-mediated hyperalgesia via GABA(A) receptors. 7. Methyleugenol has elaxant and antispasmodic actions on guinea-pig isolated ileum.

1-Aminocyclopropane-1-carboxylic acid (ACC) is an intermediate in the synthesis of ethylene, the plant hormone responsible for biological processes ranging from seed germination to organ senescence. It is a small molecule agonist at the glycine modulatory site of the NMDA receptor (EC50 = 0.7-0.9 μM) in the presence of low levels (1 μM) of glutamate and as a competitive antagonist at the glutamate-binding site on NMDA receptors (EC50 = 81.6 nM) with high levels (10 μM) of glutamate.2 This compound has been reported to protect against neuron cell death in vivo models of ischemia by enabling moderate levels of NMDA receptor activation and attenuating any excess NMDA receptor signaling that may lead to neurotoxicity.

Indole-2-carboxylic acid is an indole carboxylic acid compound with multi-target biological activity, exhibiting neuroprotective, antiviral, and antioxidant properties. Indole-2-carboxylic acid is a competitive antagonist at the glycine site of the NMDA receptor (Ki = 15 μM). Indole-2-carboxylic acid specifically inhibits the potentiating effect of glycine on NMDA-gated currents, blocking the neurotoxicity caused by excessive NMDA receptor activation, and can be used in research on the treatment of neurodegenerative diseases and cerebral ischemic injury. Indole-2-carboxylic acid is also an HIV-1 integrase inhibitor; it interferes with the integration of viral DNA into the host genome and can be used in the development of anti-HIV drugs.

PPADS tetrasodiuma is a potent P2X receptor antagonist and inhibitor of the inverse mode of Na/Ca²⁺ exchange in guinea pig airway smooth muscle and is neuroprotective against glutamate/NMDA toxicity.PPADS tetrasodiuma inhibits P2X1, P2X-2, P2X-3, and P2X- 5. 5.

DL-AP5 (2-APV) lithium is a competitive antagonist of the NMDA (N-Methyl-D-aspartate) receptor. It exhibits notable analgesic activity and specifically blocks channels in the rabbit retina.

SBI-810 hydrochloride is a β-arrestin-2 (βarr2)-biased allosteric modulator of NTSR1 (neurotensin receptor 1), exerting analgesic effects through peripheral and central mechanisms by inhibiting excitatory synaptic transmission, suppressing NMDA receptor and ERK signalling in spinal nociceptive neurons, and reducing Nav1.7 expression and action potential discharge in primary sensory neurons.

NMDA agonist 2 (compound 8d) effectively inhibits NMDA receptors, exhibiting an EC50 of 0.034 μM for GluN1/2C. It plays a significant role in neurological and psychiatric disorders.

Ensaculin is a NMDA antagonist and a 5HT1A agonist potentially for the treatment of Alzheimer's disease (AD). Ensaculin showed memory-enhancing effects in paradigms of passive and conditioned avoidance in both normal and artificially amnesic rodents. It e

glycine (2-Aminoacetic acid) is a non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter.

Psychotridine is an alkaloid that has been found inP. forsterianaand has diverse biological activities.1,2,3It inhibits ADP-, collagen-, or thrombin-induced aggregation of washed isolated human platelets with IC50values of 1.4, 1.4, and 3.9 μM, respectively.1Psychotridine (2.5 or 5 μM) is cytotoxic to HTC rat hepatocellular carcinoma cells.2It reduces paw licking induced by capsaicin in mice when administered at doses of 0.5, 2.5, or 5 mg/kg.3 1.Beretz, A., Roth-Georger, A., Corre, G., et al.Polyindolinic alkaloids from Psychotria forsteriana. Potent inhibitors of the aggregation of human plateletsPlanta Med.51(4)300-303(1985) 2.Roth, A., Kuballa, B., Bounthanh, C., et al.Cytotoxic activity of polyindoline alkaloids of Psychotria forsteriana (Rubiaceae) (1)Planta Med.6450-453(1986) 3.Amador, T.A., Verotta, L., Nunes, D.S., et al.Involvement of NMDA receptors in the analgesic properties of psychotridinePhytomedicine8(3)202-206(2001)

Alaproclate is a selective serotonin reuptake inhibitor (SSRI).1,2 It inhibits depletion of serotonin (5-HT) induced by 4-methyl-α-ethyl-m-tyramine in rat cerebral cortex, hippocampus, hypothalamus, and striatum (EC50s = 18, 4, 8, and 12 mg/kg, respectively).1 Alaproclate inhibits NMDA-evoked currents and depolarization-induced voltage-dependent potassium currents in rat hippocampal neurons (IC50s = 1.1 and 6.9 μM, respectively) and does not inhibit GABA-evoked currents when used at concentrations up to 100 μM.2 It increases sirtuin 1 (SIRT1) levels in N2a murine neuroblastoma cells expressing apolipoprotein E4 (ApoE4; IC50 = 2.3 μM) and in the hippocampus in the FXFAD-ApoE4 transgenic mouse model of Alzheimer's disease when administered at a dose of 20 mg/kg twice daily.3 Alaproclate (40 mg/kg) decreases immobility time in the forced swim test in rats, indicating antidepressant-like activity.4References1. Michael, G.B., Eidam, C., Kadlec, K., et al. Increased MICs of gamithromycin and tildipirosin in the presence of the genes erm(42) and msr(E)-mph(E) for bovine Pasteurella multocida and Mannheimia haemolytica. Journal of Antimicrobial Chemotherapy 67(6), 1555-1557 (2012).2. Svensson, B.E., Werkman, T.R., and Rogawski, M.A. Alaproclate effects on voltage-dependent K+ channels and NMDA receptors: Studies in cultured rat hippocampal neurons and fibroblast cells transformed with Kv1.2 K+ channel cDNA. Neuropharmacology 33(6), 795-804 (1994).3. Campagna, J., Soilman, P., Jagodzinska, B., et al. A small molecule ApoE4-targeted therapeutic candidate that normalizes sirtuin 1 levels and improves cognition in an Alzheimer's disease mouse model. Sci. Rep. 8(1), 17574 (2018).4. Danysz, W.P., A., Kostowski, W., Malatynska, E., et al. Comparison of desipramine, amitriptyline, zimeldine and alaproclate in six animal models used to investigate antidepressant drugs. Pharmacol. Toxicol. 62(1), 42-50 (1988). Alaproclate is a selective serotonin reuptake inhibitor (SSRI).1,2 It inhibits depletion of serotonin (5-HT) induced by 4-methyl-α-ethyl-m-tyramine in rat cerebral cortex, hippocampus, hypothalamus, and striatum (EC50s = 18, 4, 8, and 12 mg/kg, respectively).1 Alaproclate inhibits NMDA-evoked currents and depolarization-induced voltage-dependent potassium currents in rat hippocampal neurons (IC50s = 1.1 and 6.9 μM, respectively) and does not inhibit GABA-evoked currents when used at concentrations up to 100 μM.2 It increases sirtuin 1 (SIRT1) levels in N2a murine neuroblastoma cells expressing apolipoprotein E4 (ApoE4; IC50 = 2.3 μM) and in the hippocampus in the FXFAD-ApoE4 transgenic mouse model of Alzheimer's disease when administered at a dose of 20 mg/kg twice daily.3 Alaproclate (40 mg/kg) decreases immobility time in the forced swim test in rats, indicating antidepressant-like activity.4 References1. Michael, G.B., Eidam, C., Kadlec, K., et al. Increased MICs of gamithromycin and tildipirosin in the presence of the genes erm(42) and msr(E)-mph(E) for bovine Pasteurella multocida and Mannheimia haemolytica. Journal of Antimicrobial Chemotherapy 67(6), 1555-1557 (2012).2. Svensson, B.E., Werkman, T.R., and Rogawski, M.A. Alaproclate effects on voltage-dependent K+ channels and NMDA receptors: Studies in cultured rat hippocampal neurons and fibroblast cells transformed with Kv1.2 K+ channel cDNA. Neuropharmacology 33(6), 795-804 (1994).3. Campagna, J., Soilman, P., Jagodzinska, B., et al. A small molecule ApoE4-targeted therapeutic candidate that normalizes sirtuin 1 levels and improves cognition in an Alzheimer's disease mouse model. Sci. Rep. 8(1), 17574 (2018).4. Danysz, W.P., A., Kostowski, W., Malatynska, E., et al. Comparison of desipramine, amitriptyline, zimeldine and alaproclate in six animal models used to investigate antidepressant drugs. Pharmacol. Toxicol. 62(1), 42-50 (1988).

NMDA receptor antagonist 2 is a highly potent and orally active NR2B subtype-selective antagonist of the N-methyl-D-aspartate (NMDA) receptor, with an IC50 of 1.0 nM and a Ki value of 0.88 nM. This compound is valuable in scientific investigations of neuropathic pain and Parkinson's disease.

Aminoadipic acid (DL-2-Aminoadipic acid) (2-aminoadipate) is a metabolite in the principal biochemical pathway of lysine. It is an intermediate in the metabolism (i.e. breakdown or degradation) of lysine and saccharopine. It antagonizes neuroexcitatory activity modulated by the glutamate receptor N-methyl-D-aspartate (NMDA). Aminoadipic acid has also been shown to inhibit the production of kynurenic acid, a broad spectrum excitatory amino acid receptor antagonist, in brain tissue slices.

5-(2-furyl)-N-propylisoxazole-3-carboxamide is a compound used as a molecular structural unit and is thought to be a modulator of NMDA receptors, and has been shown to be protective against glutamate-induced excitotoxicity and oxidative stress in neuronal cells. It has also been found to have anti-inflammatory activity, making it a potential therapeutic agent for diseases such as Alzheimer's disease and Parkinson's disease.

Procyclidine (Tricyclamol; (±)-Procyclidine) is an anticholinergic agent that functions as a muscarinic receptor antagonist and an N-methyl-D-aspartate (NMDA) antagonist. It is used in studies of Parkinson's disease and related psychiatric disorders, including Soman-induced epilepsy [1][2].

1. Rhynchophylline (Mitrinermine) can protect against ischemic damage, probably via regulating the Akt/mTOR pathway. 2. Rhynchophylline can protect against glutamate-induced neuronal death, can inhibit MA impairment in cultured neurons in vitro. 3. Rhynchophylline and isorhynchophylline have a non-competitive antagonistic effect on the NMDA-type ionotropic glutamate receptors, suggest that these alkaloids exert their protective action against ischemia-induced neuronal damage by preventing NMDA, muscarinic M1, and 5-HT2 receptors-mediated neurotoxicity during ischemia.

1. Praeruptorin C has been widely used as an antioxidant and a calcium antagonist to treat diseases. 2. Praeruptorin C partially protects cortical neurons by inhibiting the expression of GluN2B-containing NMDA receptors and regulating the Bcl-2 family. 3.

GYKI 52466 is an allosteric AMPA receptor antagonist. It selectively inhibits AMPA-induced inward currents (IC50 = 7.5 µM) over NMDA- or GABA-induced inward currents in primary rat hippocampal neurons at 50 µM but also inhibits kainate-induced inward currents in the same cells (IC50 = 11 µM).2 GYKI 52466 (10 µM) reduces the amplitude of spontaneous excitatory postsynaptic currents (EPSCs) in the same cells. It increases the latency to seizure onset and reduces mortality in a rat model of generalized tonic-clonic seizures induced by 4-aminopyridine (4-AP) when administered at doses of 25 and 50 mg/kg. GYKI 52466 (30 mg/kg) prevents neuronal damage in the CA1 region of the hippocampus in a rat model of global ischemia-reperfusion injury induced by four-vessel occlusion.

NMDAR/TRPM4-IN-2 is a potent interfacial inhibitor of NMDAR/TRPM4 interaction.NMDAR/TRPM4-IN-2 protects against MCAO-induced brain damage and NMDA-induced retinal ganglion cell loss in mice.NMDAR/TRPM4-IN-2 has neuroprotective activity against NMDA-induced hippocampal neuronal cell death and mitochondrial dysfunction. NMDAR/TRPM4-IN-2 showed neuroprotective activity against NMDA-induced cell death and mitochondrial dysfunction in hippocampal neurons with an IC50 value of 2.1 μM.

L-Homocysteic acid is an endogenous excitatory amino acid that acts as an NMDA receptor agonist with an EC50 of 14 μM. L-Homocysteic acid is neurotoxic and can be used in neurological disease-related research.

Conantokin G TFA, a 17-amino-acid peptide, is a potent, selective, and competitive antagonist of N-Methyl-D-Aspartate (NMDA) receptors, inhibiting NMDA-evoked currents in murine cortical neurons at an IC50 of 480 nM, and exhibiting neuroprotective properties [1] [2].