Flupirtine hydrochloride
Flupirtine (D 9998) hydrochloride is an orally active, blood-brain barrier-crossing non-opioid analgesic and neuroprotective agent. Flupirtine hydrochloride is a neuronal potassium channel opener (Kv7 activator), a NMDA receptor antagonist and a GABA receptor activator. Flupirtine hydrochloride stabilizes blood-brain-barrier integrity, reduces oxidative stress and brain leukocyte infiltration, enhances angioneurogenesis, suppresses calcium influx, stabilizes neuronal resting membrane potential, and counteracts focal cerebral ischemia. Flupirtine hydrochloride exhibits analgesic, muscle relaxant properties, protects neurons from excitotoxic, ischemic, or cytokine-mediated death. Flupirtine hydrochloride functions as a non-opioid analgesic without antipyretic or antiphlogistic properties, shows no relevant affinity to opiate receptor. Flupirtine hydrochloride can be used for the research of focal cerebral ischemia, pain, Alzheimer’s disease, or multiple sclerosis.
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- No. CAS: 33400-45-2
- Fòrmula: C15H18ClFN4O2
- Peso molecular:340.78
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Almacenamiento:
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Actividad biológica
Descripciòn
In Vitro
Flupirtine (0.1-100 μM for tsA cells; 3-30 μM for SCG neurons; 3-30 μM for hippocampal, DRG, DH neurons) hydrochloride enhances currents through KV7 channels in tsA 201 cells expressing KV7.2/7.3 subunits, rat SCG neurons, hippocampal neurons, DRG neurons, and DH neurons with EC50 values ranging from 4.4 to 6.1 μM[2].
Flupirtine (10, 30 μM) hydrochloride modulates GABAA receptors (enhancing low-concentration GABA currents) and NMDA receptors (inhibiting at 30 μM) but not TRPV1, non-NMDA glutamate, or glycine receptors in rat hippocampal neurons[2].
Flupirtine (30 μM) hydrochloride potentiates GABAA receptors in rat DRG, DH, and SCG neurons, with greater leftward shifts of GABA concentration-response curves in DRG and DH neurons than SCG neurons[2].
Flupirtine (0.1-100 μM) hydrochloride is more potent at enhancing GABAA receptor currents in rat DRG neurons (EC50 22 μM) than DH (EC50 53 μM) or hippocampal (EC50 65 μM) neurons, and therapeutic concentrations (3 μM) facilitate KV7 channels and GABAA receptors similarly in DRG/DH neurons[2].
Flupirtine (10-300 μM; 1.5 minutes) hydrochloride antagonizes NMDA-induced currents in cultured rat superior colliculus neurones with an IC50 of 182.1 μM for steady-state responses and 228.6 μM for peak responses[3].
Flupirtine (0.001-10 mM; 24 h) hydrochloride inhibits the growth of U373 MG cells with a GI50 of 0.47 mM, showing significant growth reduction at 1 and 10 mM after 24 h[4].
Flupirtine (1 mM; 24, 48 h) hydrochloride alters the cell cycle distribution of U373 MG cells, decreasing the percentage of cells in the G0-G1 phase compared to control after 24 and 48 h, with significant variations in cell cycle phases observed after 48 h[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:U373 malignant glioma (MG) cells
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Concentration:0.001, 0.01, 0.1, 1, and 10 mM
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Incubation Time:24 h
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Result:Inhibited U373 MG cell growth with a GI50 of 0.47. Significantly reduced cell growth at high doses (1 and 10 mM) compared to low doses (0.001 to 0.1 mM) and control.
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Cell Line:U373 malignant glioma (MG) cells
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Concentration:1 mM
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Incubation Time:24 h; 48 h
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Result:Detected G0-G0 phase percentage of 45.48, Sub G0-G0 phase percentage of 2.49, S phase percentage of 24.47, and G₂-M phase percentage of 27.56 after 24 h treatment. Detected G0-G1 phase percentage of 56.39, Sub G0-G1 phase percentage of 1.82, S phase percentage of 18.99, and G2-M phase percentage of 22.80 after 48 h treatment. Observed significant variations in cell cycle phases after 48 h but not 24 h of treatment.
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL6 (male, 22-25 g, transient focal cerebral ischemia via left middle cerebral artery thread occlusion for 30 min)[1]
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Dosage:1, 5, 10 mg/kg; 10 mg/kg (majority of experiments)
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Administration:i.p.; single dose; during reperfusion or at 3, 6, 9, 12 h post-stroke (9 h post-stroke for majority of experiments)
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Result:Reduced infarct volumes on day 2 post-stroke at 5 and 10 mg/kg (1 mg/kg had no effect); reduced infarct volumes, TUNEL+ cell counts, rt-PA-induced acute brain toxicity, Evans blue extravasation, oxidative stress (TBARS formation), intracerebral leukocyte infiltration, calpain activity, JNK and NF-κB activation, and proteasomal activity at 10 mg/kg (given up to 9 h post-stroke); increased STAT6 abundance, neuronal density (NeuN+ cells), CD31+ endothelial cells, Dcx+ immature neurons, and BrdU+/NeuN+ mature neurons on day 84; improved performance in rota rod, tight rope, corner turn, and foot fault tests up to day 84 at 10 mg/kg (given up to 9 h post-stroke).
Chemical Information
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No. CAS 33400-45-2
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Peso molecular 340.78
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Fòrmula C15H18ClFN4O2
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SMILES
O=C(NC1=CC=C(NCC2=CC=C(C=C2)F)N=C1N)OCC.Cl
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Synonyms
D 9998 hydrochloride
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Referencias
[1]. Jaeger HM, et al. The indirect NMDAR inhibitor flupirtine induces sustained post-ischemic recovery, neuroprotection and angioneurogenesis. Oncotarget. 2015;6(16):14033-14044. [Content Brief]
[2]. Klinger F, et al. Concomitant facilitation of GABAA receptors and KV7 channels by the non-opioid analgesic flupirtine. Br J Pharmacol. 2012;166(5):1631-1642. [Content Brief]
[3]. Kornhuber J, et al. Flupirtine shows functional NMDA receptor antagonism by enhancing Mg2+ block via activation of voltage independent potassium channels. Rapid communication. J Neural Transm (Vienna). 1999;106(9-10):857-67. [Content Brief]
[4]. Panchanathan E, et al. Effect of flupirtine on the growth and viability of U373 malignant glioma cells. Cancer Biol Med. 2013;10(3):142-147. [Content Brief]
[5]. Dörr J, et al. Disease Modification in Multiple Sclerosis by Flupirtine-Results of a Randomized Placebo Controlled Phase II Trial. Front Neurol. 2018;9:842. Published 2018 Oct 9. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Flupirtine hydrochloride Related Classifications
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