'Butamben, a specific local anesthetic and aspecific ion channel modulator'

Abstract

Butamben is a local anesthetic with some unusual characteristics. Epidural application in the form of a suspension leads to long-term selective pain suppression, leaving the motor system intact. The mechanism behind this selective behavior is not understood. In order to see whether this selectivity can be traced back to a selective action on ion channels, the effect of butamben was studied on several ion channels. This thesis describes the modulating effects of butamben on voltage-gated calcium channels, with N-, L- and T-type in particular. Furthermore, its effects on the voltage-gated potassium channels Kv1.1 and hERG are described. Butamben affects the different studied ion channels all in a likewise manner. Clinically relevant concentrations speed up the gating kinetics and reduce the overall current amplitude. The data suggest that butamben biases ion channels towards intermediate closed states It is unlikely that butamben displays its current modulating effects through specific butamben receptors. The selective analgesic action of butamben probably relies on relatively aspecific ion current inhibition at a specific stable concentration.