:
Mexiletine is an antiarrhythmic drug belonging to IB class, acting as sodium channel blocker.
Besides its well-known activity on arrhythmias, its usefulness in the treatment of myotonia,
myotonic distrophy and amyotrophic lateral sclerosis is now widely recognized. Nevertheless, it has
been retired from the market in several countries because of its undesired effects. Thus, several
papers were reported in the last years about analogues and homologues of mexiletine being
endowed with a wider therapeutic ratio and a more selectivity of action. Some of them showed
sodium channel blocking activity higher than the parent compound. It is noteworthy that mexiletine
is used in therapy as a racemate even though a difference in the activities of the two enantiomers
were widely demonstrated, with (–)-(R)-enantiomer being more active: this finding led several
research groups to study mexiletine and its analogues and homologues in their optically active
forms. This review summarizes the different synthetic routes used to obtain these compounds. They
could represent an interesting starting point to new mexiletine-like compounds without common
side effects related to the use of mexiletine.