title: Sodium channel activity and sigma binding of 2-aminopropanamide anticonvulsants.
abstract: Sodium channel blocking, anticonvulsant activity, and sigma (sigma) binding of selected leads in a series of alpha-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 sigma1 binding. Both anticonvulsant and Na+ channel blocking activities were independent of stereochemistry, while sigma1 binding seems to be favoured by an S-configuration on the aminoamide moiety.
authors.affiliation: Pharmacia & Upjohn, Chem. Dept., Milan, Italy. paolo.pevarello@eu.pnu.com
authors.forename: P
authors.initials: P
authors.lastname: Pevarello
authors.forename: A
authors.initials: A
authors.lastname: Bonsignori
authors.forename: C
authors.initials: C
authors.lastname: Caccia
authors.forename: R
authors.initials: R
authors.lastname: Amici
authors.forename: R A
authors.initials: RA
authors.lastname: McArthur
authors.forename: R G
authors.initials: RG
authors.lastname: Fariello
authors.forename: P
authors.initials: P
authors.lastname: Salvati
authors.forename: M
authors.initials: M
authors.lastname: Varasi
mesh_terms: D000577:Amides / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017480:Receptors, sigma / Q000378:metabolism*; D026941:Sodium Channel Blockers
chemical_list: D000577:Amides; D000927:Anticonvulsants; D017480:Receptors, sigma; D026941:Sodium Channel Blockers