Synthesis and in vitro sodium channel blocking activity evaluation of novel homochiral mexiletine analogs.
New chiral mexiletine analogs were synthesized in their optically active forms and evaluated in vitro as use-dependent blockers of skeletal muscle sodium channels. Tests carried out on sodium currents of single muscle fibers of Rana esculenta demonstrated that all of them exerted a higher use-dependent block than mexiletine. The most potent analog, (S)-3-(2,6-dimethylphenoxy)-1-phenylpropan-1-amine (S)-(5), was six-fold more potent than (R)-Mex in producing a tonic block. As observed with mexiletine, the newly synthesized compounds exhibit modest enantioselective behavior, that is more evident in 3-(2,6-dimethylphenoxy)butan-1-amine (3).
Carocci
Alessia
A
Dipartimento Farmaco-Chimico, Facoltà di Farmacia, Università degli Studi di Bari, Bari, Italy. carocci@farmchim.uniba.it
Catalano
Alessia
A
Bruno
Claudio
C
Lentini
Giovanni
G
Franchini
Carlo
C
De Bellis
Michela
M
De Luca
Annamaria
A
Conte Camerino
Diana
D
D000818:Animals; D008801:Mexiletine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology*; D009132:Muscles / Q000187:drug effects*; D009222:Myotonia / Q000188:drug therapy*; D026941:Sodium Channel Blockers / Q000494:pharmacology*
D026941:Sodium Channel Blockers; D008801:Mexiletine