kv7.5

Flindokalner (BMS-204352) is a potassium channel modulator and a positive modulator of all neuronal Kv7 channel subtypes expressed in HEK293 cells. It is also a positive modulator of large conductance calcium-activated K channels (BKca) and displays negative modulatory activity at Kv7.1 channels (Ki = 3.7 μM). Additionally, Flindokalner acts as a negative modulator of GABAA receptors and demonstrates anxiolytic efficacy in vivo.

Kv7.2/Kv7.3 activator-3 (GRT-X) is an orally active activator of Kv7.2/Kv7.3 channels and the TSPO. It activates Kv7.2/Kv7.3, Kv7.4, and Kv7.5 with EC50 values of 0.37, 2.06, and 0.75 μM, respectively, and binds to TSPO with Ki values of 0.07 μM (rat membrane) and 4.60 μM (human U-118 MG cells). This compound protects motor neurons from degeneration caused by exposure to astrocyte-conditioned media from mice and humans with amyotrophic lateral sclerosis/frontotemporal dementia. Additionally, Kv7.2/Kv7.3 activator-3 stimulates axonal growth in dorsal root ganglia through TSPO and Kv7.2/3 activation and exhibits anticonvulsant effects in epilepsy models. It alleviates hyperalgesia in diabetic neuropathy patients, enhances the survival and regeneration of neurons after cervical neuropathy in rats, and accelerates the recovery of normal function in sensory and motor neurons.