Guanidine is a small molecule oral medication that has been used to treat the symptoms of Lambert-Eaton myasthenic syndrome (LEMS), a rare autoimmune disease that weakens muscles mainly in the lower limbs. Guanidine is one of the byproducts of protein metabolism that is excreted naturally in urine.

How guanidine works

LEMS is caused by autoantibodies that bind to proteins called voltage-gated calcium channels (VGCCs) in the nerve cell endings. This blocks the release of vesicles containing the neurotransmitter (cell-signaling molecule) acetylcholine from the nerve cell terminals into the synaptic space at the neuromuscular junction, which is where nerve cells and muscles meet. Acetylcholine is required for muscles to contract. The binding of the autoantibodies to VGCCs causes the muscles not to receive nerve cell signals to contract, resulting in symptoms such as severe muscle weakness and fatigue.

Guanidine binds to another type of channel protein at the neuromuscular junction, called potassium channels, and prolongs the nerve signal. This facilitates the uptake (absorption) of calcium by the remaining healthy calcium channels. That action stimulates the release of vesicles containing acetylcholine into the synaptic space in the neuromuscular junction and helps muscles contract.

Guanidine and clinical studies

While several case reports have shown that guanidine improves electromyographic parameters and muscle strength, it can cause serious side effects, especially related to blood disorders and kidney failure. Therefore, it is not the preferred option for LEMS therapy.

A study published in the journal Muscle & Nerve showed that a combination treatment of low-dose guanidine and pyridostigmine was relatively safe and effective in the long-term treatment of LEMS patients. In that study, nine patients were treated for three to 102 months with pyridostigmine and a daily dose of guanidine below 1,000 mg. Guanidine was given between the pyridostigmine doses. This combination therapy improved the clinical status of all patients. While three patients had to drop out of the study because of intestinal problems, no kidney or blood disease was observed.

In another study, also published in Muscle & Nerve, a patient with LEMS treated daily with low-dose guanidine developed neutropenia (very low number of white blood cells called neutrophils). However, a shift to alternate-day low-dose guanidine therapy was successful.

Other details about guanidine

Guanidine can cause serious side effects such as nausea, vomiting and diarrhea, bone marrow suppression that can cause blood disorders including anemia, low white blood cell count, and kidney insufficiency. That is why guanidine is not preferred for long-term treatment of LEMS.


Last updated: July 24, 2019


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