Flupirtine hydrochloride  (Synonyms: D 9998 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^{[1][2][3][4][5]}.

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 K_V7 channels in tsA 201 cells expressing K_V7.2/7.3 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 GABA_A 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 GABA_A 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 GABA_A 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 K_V7 channels and GABA_A 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.

Flupirtine (1-10 mg/kg; i.p.; single dose; up to 9 h post-stroke) hydrochloride induces sustained neuroprotection, enhanced neurological recovery, and angioneurogenesis in mice with transient focal cerebral ischemia, with 10 mg/kg being the most effective dose^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

340.78

C₁₅H₁₈ClFN₄O₂

33400-45-2

O=C(NC1=CC=C(NCC2=CC=C(C=C2)F)N=C1N)OCC.Cl

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [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]