Flupirtine (Maleate)

Flupirtine Maleate is an orally active, blood-brain barrier-crossing non-opioid analgesic and neuroprotective agent. Flupirtine Maleate is a neuronal potassium channel opener (Kv7 activator), a NMDA receptor antagonist and a GABA receptor activator. Flupirtine Maleate 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 Maleate exhibits analgesic, muscle relaxant properties, protects neurons from excitotoxic, ischemic, or cytokine-mediated death. Flupirtine Maleate functions as a non-opioid analgesic without antipyretic or antiphlogistic properties, shows no relevant affinity to opiate receptor. Flupirtine Maleate can be used for the research of focal cerebral ischemia, pain, Alzheimer’s disease, or multiple sclerosis^{[1][2][3][4][5]}. In Vitro:Flupirtine (0.1-100 μM for tsA cells; 3-30 μM for SCG neurons; 3-30 μM for hippocampal, DRG, DH neurons) Maleate 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) Maleate 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) Maleate 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) Maleate 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) Maleate 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) Maleate 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) Maleate 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]. In Vivo:Flupirtine (1-10 mg/kg; i.p.; single dose; up to 9 h post-stroke) Maleate 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].