Mexiletine Helps Beat A Charley Horse, ALS Specialists Say

Staying calm? Mexiltine may help alleviate muscle cramps in ALS by reducing the hyperexcitability of the peripheral nerves (see also February 2017 news). The strategy is thought to reduce the increased influx of sodium ions into the distal axons of motor neurons, which may cause muscle cramps in the disease (Kanai et al., 2006). [Image: Courtesy of Nature Publishing Group. Reproduced with Permission.]

Mexiletine may help reduce a key source of pain in people with ALS according to a new study led by the Bjorn Oskarsson, now at the Mayo Clinic in Jacksonville, Florida. The drug, taken at a dose of 300 mg/daily, reduced the average number of muscle cramps by 33% compared to placebo according to a phase 4 clinical trial analysis. 20 people with ALS participated in the 6-week study.

The results add to growing evidence that mexiletine helps alleviate muscle cramps in at least some people with the disease (Weiss et al., 2016).

Mexiletine is emerging as a key alternative to quinine, which according to a warning issued in 2006 by the FDA, may result in potentially life-threatening complications including in the blood and the heart (Katzberg et al., 2010). The strategy is based on a small clinical study conducted by Kazuaki Kanai and colleagues at Chiba University School of Medicine in Japan in 2003, which found that mexiletine helped relieve muscle cramps in 8 people with spinocerebellar ataxia Type 3 (Kanai et al., 2003).

Muscle cramps are a major source of pain for about 1 out of 4 people with ALS (Caress et al., 2016).

The findings appeared on March 6 in Muscle and Nerve.

Mexiletine is a use-dependent sodium channel blocker that is FDA-approved for the treatment of cardiac arrhythmia. The approach is also emerging as a key therapeutic option to reduce muscle stiffness (myotonia) in rare muscle disorders including myotonic dystrophy type 1 (Logigian et al., 2010; Statland et al., 2012; for review, see Dowling et al., 2017).


To learn more about mexiletine, check out Mexiletine Alleviates Key Source of Muscle Pain in ALS.

Featured Paper

 Oskarsson B, Moore D, Mozaffar T, Ravits J, Wiedau-Pazos M, Parziale N, Joyce NC, Mandeville R, Goyal N, Cudkowicz ME, Weiss M, Miller RG, McDonald CM. Mexiletine for Muscle Cramps in ALS: A Randomized Double-Blind Crossover Trial. Muscle Nerve. 2018 Mar 6. [PubMed].


Weiss MD, Macklin EA, Simmons Z, Knox AS, Greenblatt DJ, Atassi N, Graves M, Parziale N, Salameh JS, Quinn C, Brown RH Jr, Distad JB, Trivedi J, Shefner JM, Barohn RJ, Pestronk A, Swenson A, Cudkowicz ME; Mexiletine ALS Study Group. A randomized trial of mexiletine in ALS: Safety and effects on muscle cramps and progression. Neurology. 2016 Apr 19;86(16):1474-81. [PubMed].

Kanai K, Kuwabara S, Arai K, Sung JY, Ogawara K, Hattori T. Muscle cramp in Machado-Joseph disease: altered motor axonal excitability properties and mexiletine treatment. Brain. 2003 Apr;126(Pt 4):965-73. [PubMed]

Kanai K, Kuwabara S, Misawa S, Tamura N, Ogawara K, Nakata M, Sawai S, Hattori T, Bostock H. Altered axonal excitability properties in amyotrophic lateral sclerosis: impaired potassium channel function related to disease stage. Brain. 2006 Apr;129(Pt 4):953-62. [PubMed].

Caress JB, Ciarlone SL, Sullivan EA, Griffin LP, Cartwright MS. Natural history of muscle cramps in amyotrophic lateral sclerosis. Muscle Nerve. 2016 Apr;53(4):513-7. [PubMed].

Further Reading

Chiò A, Mora G, Lauria G. Pain in amyotrophic lateral sclerosis. Lancet Neurol. 2017 Feb;16(2):144-157. [PubMed].

Logigian EL, Martens WB, Moxley RT 4th, McDermott MP, Dilek N, Wiegner AW, Pearson AT, Barbieri CA, Annis CL, Thornton CA, Moxley RT 3rd. Mexiletine is an effective antimyotonia treatment in myotonic dystrophy type 1. Neurology. 2010 May 4;74(18):1441-8. doi: 10.1212/WNL.0b013e3181dc1a3a.

Statland JM, Bundy BN, Wang Y, Rayan DR, Trivedi JR, Sansone VA, Salajegheh MK, Venance SL, Ciafaloni E, Matthews E, Meola G, Herbelin L, Griggs RC, Barohn RJ, Hanna MG; Consortium for Clinical Investigation of Neurologic Channelopathies. Mexiletine for symptoms and signs of myotonia in nondystrophic myotonia: a randomized controlled trial. JAMA. 2012 Oct 3;308(13):1357-65. [PubMed].


disease-als disease-myotonicdystrophy disease-spinocerebellar-ataxia hyperexcitability ion channels mexiletine muscle cramps myotonia pain
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