Sodium channel activity and sigma binding of 2-aminopropanamide anticonvulsants

Sodium channel blocking, anticonvulsant activity, and sigma (σ) binding of selected leads in a series of α-amino amide anticonvulsants were examined. While anticonvulsant compounds were always endowed with low micromolar sodium (Na+) channel site-2 binding, compounds with low site-2 Na+ channel affinity failed to control seizures. No correlation could be drawn with σ1 binding. Both anticonvulsant and Na+ channel blocking activities were independent of stereochemistry, while σ1 binding seems to be favoured by an S-configuration on the amino amide moiety.