Flupirtine-d4 is intended for use as an internal standard for the quantification of flupirtine by GC- or LC-MS. Flupirtine is an activator of voltage-gated potassium channel 7 (Kv7/KCNQ).1,2,3 It induces relaxation of preconstricted pulmonary arteries isolated from wild-type and serotonin transporter-overexpressing (SERT+) mice.2 Flupirtine (30 mg/kg per day) decreases mean right ventricular pressure and right ventricular hypertrophy in hypoxia-induced and SERT+ mouse models of pulmonary arterial hypertension. It increases the paw withdrawal threshold in a rat model of streptozotocin-induced diabetic neuropathy when administered at a dose of 10 mg/kg and increases paw withdrawal latency in a rat model of carrageenan-induced paw inflammation when used in combination with morphine.3 Flupirtine also indirectly antagonizes NMDA receptors via its effects on potassium channels.1,4
|1. Devulder, J. Flupirtine in pain management: Pharmacological properties and clinical use. CNS Drugs 25(10), 867-881 (2010).|2. Morecroft, I., Murray, A., Nilsen, M., et al. Treatment with the Kv7 potassium channel activator flupirtine is beneficial in two independent mouse models of pulmonary hypertension. Br. J. Pharmacol. 157(7), 1241-1249 (2009).|3. Goodchild, C.S., Kolosov, A., Tucker, A.P., et al. Combination therapy with flupirtine and opioid: Studies in rat pain models. Pain Med. 9(7), 928-938 (2008).|4. Kornhuber, J., Bleich, S., Wiltfang, J., et al. Flupirtine shows functional NMDA receptor antagonism by enhancing Mg2+ block via activation of voltage independent potassium channels. J. Neural Transm. (Vienna) 106(9-10), 857-867 (1999).