Duchenne muscular dystrophy, a genetic disease caused by the absence of functional dystrophin, remains without adequate treatment. Although great hopes are attached to gene and cell therapies, identification of active small molecules remains a valid option for new treatments. We have studied the effect of 20 approved pharmaceutical compounds on the muscles of dystrophin-deficient mdx5Cv mice. These compounds were selected as the result of a prior screen of 800 approved molecules on a dystrophin mutant of the invertebrate animal model Cænorhabditis elegans. Drugs were administered to the mice through maternal feeding since 2weeks of life and mixed in their food after the 3rd week of life. The effects of the drugs on mice were evaluated both at 6weeks and 16weeks. Each drug was tested at two concentrations. Prednisone was added to the molecule list as a positive control. To investigate treatment efficiency, more than 30 histological, biochemical and functional parameters were recorded. This extensive study reveals that tricyclics (Imipramine and Amitriptyline) are beneficial to the fast muscles of mdx mice. It also highlights a great variability of responses according to time, muscles and assays.