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 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.
Pevarello
P
P
Pharmacia & Upjohn, Chem. Dept., Milan, Italy. paolo.pevarello@eu.pnu.com
Bonsignori
A
A
Caccia
C
C
Amici
R
R
McArthur
R A
RA
Fariello
R G
RG
Salvati
P
P
Varasi
M
M
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
D000577:Amides; D000927:Anticonvulsants; D017480:Receptors, sigma; D026941:Sodium Channel Blockers