Meclozine ameliorates skeletal muscle pathology and increases muscle forces in mdx mice

Biochem Biophys Res Commun. 2022 Feb 12:592:87-92. doi: 10.1016/j.bbrc.2022.01.003. Epub 2022 Jan 7.


We screened pre-approved drugs for the survival of the Hu5/KD3 human myogenic progenitors. We found that meclozine, an anti-histamine drug that has long been used for motion sickness, promoted the proliferation and survival of Hu5/KD3 cells. Meclozine increased expression of MyoD, but reduced expression of myosin heavy chain and suppressed myotube formation. Withdrawal of meclozine, however, resumed the ability of Hu5/KD3 cells to differentiate into myotubes. We examined the effects of meclozine on mdx mouse carrying a nonsense mutation in the dystrophin gene and modeling for Duchenne muscular dystrophy. Intragastric administration of meclozine in mdx mouse increased the body weight, the muscle mass in the lower limbs, the cross-sectional area of the paravertebral muscle, and improved exercise performances. Previous reports show that inhibition of phosphorylation of ERK1/2 improves muscle functions in mouse models for Emery-Dreifuss muscular dystrophy and cancer cachexia, as well as in mdx mice. We and others previously showed that meclozine blocks the phosphorylation of ERK1/2 in cultured cells. We currently showed that meclozine decreased phosphorylation of ERK1/2 in muscles in mdx mice but not in wild-type mice. This was likely to be one of the underlying mechanisms of the effects of meclozine on mdx mice.

Keywords: Drug repositioning; Duchenne muscular dystrophy; Meclozine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Humans
  • Male
  • Meclizine / pharmacology*
  • Meclizine / therapeutic use
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred mdx
  • Motor Activity / drug effects
  • Muscle Development / drug effects
  • Muscle Strength / drug effects
  • Muscle Strength / physiology*
  • Muscle, Skeletal / pathology*
  • Muscle, Skeletal / physiopathology*
  • Muscular Dystrophy, Duchenne / drug therapy
  • Muscular Dystrophy, Duchenne / pathology
  • Muscular Dystrophy, Duchenne / physiopathology
  • Phosphorylation / drug effects


  • Meclizine
  • Extracellular Signal-Regulated MAP Kinases