Mexiletine is a treatment approved by the U.S. Food and Drug Administration (FDA) to treat irregular heartbeat. It may also be used to treat muscle cramps in amyotrophic lateral sclerosis (ALS).

How mexiletine works

ALS is a serious condition characterized by the progressive loss of motor neurons — the nerve cells that control muscle contraction, allowing us to move, talk, swallow, and breathe. As the motor neurons deteriorate, muscles begin to weaken and atrophy.

When muscles move, the nerve signal sent from the brain to the muscle is conducted by changing the flow of ions in and out of the nerve cells, changing the overall charge of the nerve cell and conducting the nerve message. In ALS, dying nerve cells can cause strong, irregular nerve signals to be sent to the muscles, which can cause painful muscle cramping.

Mexiletine is a sodium channel blocker; it works by inhibiting the flow of charged ions (in this case, sodium) through a protein channel in the nerve cells, slowing the conduction of a nerve impulse. It is thought that mexiletine can, therefore, reduce muscle cramps seen in ALS by reducing the faulty nerve impulses being sent to the muscles.

Mexiletine in clinical trials for ALS

A Phase 2 clinical trial (NCT01849770) tested whether mexiletine was safe and effective in people with ALS. Sixty patients were randomly assigned to receive either 300 mg per day of mexiletine, 900 mg per day of mexiletine, or a placebo for 12 weeks. Safety and tolerability were the primary outcome measures. Pharmacokinetics (movement of the drug in the body) were also assessed, as were the ALS functional rating scale-revised (ALSFRS-R) scores (a measure of disability), and muscle cramp frequency and severity.

The results were published in the journal Neurology. Only one adverse reaction was reported (a fall). Mexiletine treatment resulted in large dose-dependent reductions in muscle cramp frequency and severity. No effect on the rate of disease progression was detected at 12 weeks.

A second Phase 2 clinical trial (NCT02781454) conducted by the same research group is ongoing and expected to be completed by the end of 2018. The trial is testing whether mexiletine is effective in lowering the electrical activity of the motor neurons in people with ALS. The investigators also are searching for any signs that the treatment may slow the progression of the disease and reduce muscle cramps and muscle twitching. This will be determined through transcranial magnetic stimulation (TMS, a non-invasive method of using magnetic stimulation to measure nerve transmission in the brain) and threshold tracking nerve conduction studies (TTNCS, a way of measuring how active nerve signaling is in peripheral nerves such as arms or legs).

A Phase 4 clinical trial (NCT01811355) tested whether mexiletine was effective in treating muscle cramps in ALS patients. Twenty patients received either 150 mg of mexiletine or a placebo twice per day for two weeks. After a one-week washout period, patients who received a placebo in the first half of the trial received mexiletine and those who received the medication got the placebo. Patients kept a cramp journal, recording the number and severity of the cramps they experienced throughout the study.

The results were published in the journal Muscle & Nerve; 18 patients reported fewer muscle cramps, and four patients became cramp free. Cramp severity was significantly reduced, and treatment was well-tolerated.

Other information

Mexiletine may cause side effects, including heartburn, nausea, dizziness, tremors, and blurred vision. Patients should contact a physician immediately if they experience chest pain, irregular heartbeat, or liver problems.


ALS News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.