Molecular Pharmacology of Selective Na_V1.6 and Dual Na_V1.6/Na_V1.2 Channel Inhibitors that Suppress Excitatory Neuronal Activity Ex Vivo.

ABSTRACT: Voltage-gated sodium channel (Na_V) inhibitors are used to treat neurological disorders of hyperexcitability such as epilepsy. These drugs act by attenuating neuronal action potential firing to reduce excitability in the brain. However, all currently available Na_V-targeting antiseizure medications nonselectively inhibit the brain channels Na_V1.1, Na_V1.2, and Na_V1.6, which potentially limits the efficacy and therapeutic safety margins of these drugs. Here, we report on XPC-7724 and XPC-5462, which represent a new class of small molecule Na_V-targeting compounds. These compounds specifically target inhibition of the Na_V1.6 and Na_V1.2 channels, which are abundantly expressed in excitatory pyramidal neurons.

SUBMITTER: Goodchild SJ 

PROVIDER: S-EPMC10958515 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature