Cocaine exerts its local anaesthetic effect by blocking voltage-gated sodium channels in peripheral neurons. Cocaine diffuses across the neuronal plasma membrane in its uncharged base form. Once inside the cytoplasm, it is protonated and this protonated form enters and blocks the pore of the voltage-gated sodium channel from the cytoplasmic side. For this to happen, the sodium channel must first become active so that so that gating mechanism is in the open state. Therefore cocaine preferentially inhibits neurons that are actively firing.