SIMULATION OF ACTION-POTENTIAL DAMPING PRODUCED BY ANTICONVULSANT DRUGS

Anticonvulsant drugs reduce the ability of central neurones to sustain high-frequency repetitive firing of action potentials. In recent year s, it has been demonstrated that this effect is primarily due to a Na conductance reduction. We have simulated the electrical behaviour of a neurone, including Ca2+ and various K+ conductances. Although a redu ction of Na+ conductance produces a progressive reduction until a comp lete suppression of the action potential bust, a smaller reduction of this conductance is necessary to produce the same effect when the dela yed-rectifier K+ conductance and the Ca2+ conductance are concomitantl y reduced. The results indicate that the drugs action on conductances other than Na+ is important for determining their anticonvulsant effec t on neurones at therapeutic concentrations. (C) 1997 The Italian Phar macological Society.