Sodium channel activity and sigma binding of 2-aminopropanamide anticonvulsants

• Published in: Bioorganic & medicinal chemistry letters Vol. 9; no. 17; pp. 2521 - 2524
• Main Authors: Pevarello, Paolo, Bonsignori, Alberto, Caccia, Carla, Amici, Raffaella, McArthur, Robert A., Fariello, Ruggero G., Salvati, Patricia, Varasi, Mario
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 06.09.1999; Elsevier
• Subjects: Amides - metabolism; Amides - pharmacology; Animals; Anticonvulsants; Anticonvulsants - metabolism; Anticonvulsants - pharmacology; Anticonvulsants. Antiepileptics. Antiparkinson agents; Biological and medical sciences; Medical sciences; Neurologically active compds; Neuropharmacology; Pharmacology. Drug treatments; Rats; Receptors, sigma - metabolism; Sigma receptors; Sodium channel; Sodium Channel Blockers; Anticonvulsants; Sodium channel; Sigma receptors; Neurologically active compds; Ether; Rat; Aminoamide; Rodentia; Sigma receptor; Central nervous system; Anticonvulsant; Ionic channel; In vitro; Stereoselectivity; α-Aminoacid; Vertebrata; Biological fixation; Mammalia; Structure activity relation; Sodium; Animal; Benzenic compound; S configuration; Chemical synthesis; Brain (vertebrata)
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(99)00415-1

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 σ 1 binding. Both anticonvulsant and Na + channel blocking activities were independent of stereochemistry, while σ 1 binding seems to be favoured by an S-configuration on the amino amide moiety.