Voltage-gated calcium channels are not affected by the novel anti-epileptic drug lacosamide

The novel anti-epileptic drug lacosamide targets two proteins - voltage-gated sodium channels and collapsin response mediator protein 2 (CRMP-2) - suggesting dual modes of action for lacosamide. We recently identified the neurite outgrowth and axonal guidance protein CRMP-2 as a novel partner and regulator of the presynaptic N-type voltage-gated Ca²⁺ channel (CaV2.2) [Brittain et al., J. Biol. Chem. 284: 31375-31390 (2009)]. Here we examined the effects of lacosamide on voltage-gated Ba2+ channels. Lacosamide did not affect Ba²⁺ currents via N- and P/Q- channels in rat hippocampal neurons or L-type Ca²⁺ channels in a mouse CNS neuronal cell line, respectively. N-type Ba²⁺ currents, augmented by CRMP-2 expression, were also unaffected by acute or chronic lacosamide exposure. These results establish that the anti-epileptic mode of action of lacosamide does not involve these voltage-gated Ca²⁺ channels.