Phentolamine is a commonly used drug in clinical practice, above all to lower blood pressure through vasodilation. This vasodilatory effect leads to a faster local elimination of injected substances. Therefore, phentolamine is used to shorten the unwanted prolonged duration of local numbness, especially in minor surgical procedures such as dental treatments. In our study, we investigated the interaction of phentolamine with voltage-gated sodium channels – proteins cruxial for neuronal activity.
Using patch-clamp experiments, we demonstrated that phentolamine acts as a blocker of various subgroups of voltage-gated sodium channels. This finding is particularly interesting because local anesthetics exert their effects by blocking these very channels. As a result, this function of phentolamine could potentially counteract with its use in the shortening of local anesthesia. Through patch-clamp experiments on mutated sodium channels and computer simulations, we showed that phentolamine binds to a site on the sodium channel that is very similar to the binding site of conventional local anesthetics.
Finally, we compared other drugs from the same pharmacological class (the so-called alpha-blockers) in terms of their effects on sodium channels and found that phentolamine exhibits a particularly strong inhibitory effect on sodium currents. This suggests that it could be promising to investigate other drugs in the future for their ability to shorten local anesthesia duration.
Toklucu, I., Sudha Bhagavath Eswaran, V., Bott, R. A., Kesdoğan, A. B., Gaebler, A. J., Stingl, J., Hausmann, R., Körner, J., & Lampert, A. (2025). α-Adrenoreceptor blocker phentolamine inhibits voltage-gated sodium channels via the local anaesthetic binding site. British Journal of Pharmacology, 1–18.
