Inhibition of the Human Neuronal Sodium Channel Na1.9 by Arachidonyl-2-Chloroethylamide, An Analogue of Anandamide in a hNa1.9/rNa1.4 Chimera, An Experimental and in Silico Study.

Cannabinoids regulate analgesia, which has aroused much interest in identifying new pharmacological therapies in the management of refractory pain. Voltage-gated Na+ channels (Nas) play an important role in inflammatory and neuropathic pain. In particular, Na1.

Mefloquine inhibits voltage dependent Na1.4 channel by overlapping the local anaesthetic binding site.

Mefloquine constitutes a multitarget antimalaric that inhibits cation currents. However, the effect and the binding site of this compound on Na channels is unknown. To address the mechanism of action of mefloquine, we employed two-electrode voltage clamp recordings on Xenopus laevis oocytes, site-directed mutagenesis of the rat Na channel, and a combined in silico approach using Molecular Dynamics and docking protocols.

Predicting a double mutant in the twilight zone of low homology modeling for the skeletal muscle voltage-gated sodium channel subunit beta-1 (Nav1.4 β1).

The molecular structure modeling of the β1 subunit of the skeletal muscle voltage-gated sodium channel (Nav1.4) was carried out in the twilight zone of very low homology. Structural significance can per se be confounded with random sequence similarities.