Benzodiazepines modify evoked action potentials of the rat sciatic nervein vitro

Abstract

Diazepam, midazolam and clonazepam were examined at concentrations varying from 3.10–5 to 3.10–4 M. In the isolated rat sciatic nerve preparation all compounds produced significant time‐ and concentration‐dependent inhibition of evoked action potentials. With increasing time intervals the response became increasingly concentration‐dependent. Concentrations of 3.10–5 M of midazolam or clonazepam ‐ and diazepam, at the time intervals up to 24 min, to a lesser extent ‐ produced a slight increase of the amplitude. The time‐response curves of diazepam tended to flatten between 24 and 60 min. Clonazepam, after eliciting intitial increase at 6.10–5 M, reduced the action potentials only in the range of l.l0–4 to 3.10–4 M. The latter reduction was time‐dependent in a significant way at concentrations of 3.10–4 M. The Emax values of the benzodiazepines were increased progressively with the exposure time, i.e. that of diazepam > midazolam > clonazepam. It is concluded that, in the concentrations studied, benzodiazepines have direct time‐dependent blocking actions on nerve conduction in isolated motor nerves ‐ involving ion channel currents ‐ those of diazepam being the most potent.