Sodium channel activity and sigma binding of 2-aminopropanamide anticonvulsants

Sodium channel blocking, anticonvulsant activity, and sigma (sigma) binding of selected leads in a series of alpha-amino amide anticonvulsants were ex amined. While anticonvulsant compounds were always endowed with low micromo lar sodium (Na+) channel site-2 binding, compounds with low site-2 Na+ chan nel affinity failed to control seizures. No correlation could be drawn with sigma(1) binding. Both anticonvulsant and Na+ channel blocking activities were independent of stereochemistry, while sigma(1) binding seems to be fav oured by an S-configuration on the aminoamide moiety. (C) 1999 Elsevier Sci ence Ltd. All rights reserved.