Upcoming Webinar: Probing Sodium Channel Blockers In Vivo: TMS Strength–Duration Metrics as a Translational Biomarker

Dr Lorenzo Rocchi

30th of October, 2025

This webinar will introduce a novel approach using transcranial magnetic stimulation (TMS) with variable pulse widths to probe sodium channel function in vivo. By analysing strength–duration properties of cortical neurons, we explore whether this technique can serve as a pharmacodynamic biomarker, offering a new window into how drugs work in the human brain.

Join us to learn how this method could advance early-phase trials, differentiate between similar compounds, and support more personalized strategies in epilepsy drug development.

Register now

Research background:

Voltage-gated sodium channels (VGSCs) are fundamental determinants of neuronal excitability and central targets of many antiseizure medications. While preclinical models and in vitro studies have advanced our understanding of VGSC pharmacology, translating these findings to the intact human brain has remained challenging. Conventional measures, such as single TMS-derived motor thresholds, can detect general reductions in cortical excitability but often lack the specificity needed to differentiate between drug mechanisms.

In this study, we employed a novel transcranial magnetic stimulation (TMS) device capable of varying pulse width to characterize the strength–duration behavior of human cortical neurons. This approach provides access to rheobase and the strength–duration time constant (SDTC), parameters closely linked to axonal sodium channel function. We examined the acute effects of carbamazepine and lacosamide, two widely used antiseizure drugs with distinct pharmacological profiles.

Both drugs increased motor thresholds, confirming reduced cortical excitability. However, strength–duration curves revealed divergent mechanisms: lacosamide reduced SDTC and increased rheobase in a manner consistent with selective sodium channel blockade, while carbamazepine had minimal impact on these parameters despite lowering excitability. These findings suggest that strength–duration metrics can uncover drug-specific actions that are not evident from conventional TMS measures—or from animal and in vitro data alone.

From a clinical trial perspective, this work highlights the potential of TMS as a noninvasive pharmacodynamic biomarker. TMS can probe ion channel function in vivo, in the human brain, with a temporal resolution suitable for early-phase studies. Such measures can (1) clarify mechanisms of action, (2) differentiate compounds with superficially similar effects, and (3) inform dose selection and patient stratification. Importantly, they complement rather than replace preclinical models, offering a bridge between mechanistic insights and clinical translation.

Overall, TMS-based strength–duration analysis emerges as a promising tool for clinical research, capable of guiding the development and evaluation of novel therapeutics. By detecting subtle, mechanism-specific effects of sodium channel modulators in humans, this approach paves the way for more targeted, data-driven strategies in drug development and personalized medicine.