Effect of tolperisone on the resting brain and on evoked responses, an phMRI BOLD study

Tolperisone is a voltage gated sodium channel blocker, centrally acting muscle relaxant drug, with a very advantageous side effect profile. Like other sodium channel blockers, it has weak affinity to the resting state and high affinity to the open/inactivated state of the channel. In this paper, its effect on BOLD responses in rat brain were elucidated both on the resting brain and paw stimulation evoked BOLD responses. Tolperisone did not exert any visible effect on resting brain, but strongly inhibited the paw stimulation evoked BOLD responses, showing somewhat higher efficacy in brain areas involved in pain sensation. This finding is in a good agreement with its sodium channel blocking profile. In the resting brain, most of the channels are in resting state. Electric train stimuli of the paw results in over activated neurons, where most sodium channels are in open or inactivated state. These data suggest that the very advantageous profile of tolperisone can be explained by its selective action on open or inactivated sodium channels of over-activated neurons in various brain regions rather than by a selective effect in the spinal cord as suggested previously.