If you have been diagnosed with myasthenia gravis (MG), you may have been prescribed either pyridostigmine or neostigmine (marketed as Mestinon and Bloxiverz, respectively). These drugs are known as cholinesterase inhibitors. What are they, and how do they work?
The neuromuscular junction in myasthenia gravis
To understand why cholinesterase inhibitors are frequently prescribed in MG, it is important to have a basic understanding of how MG causes muscle weakness and other symptoms.
The neuromuscular junction is the area where the nerve meets the muscle. In order for your muscle to be activated, it needs to receive a signal from the nerves. This signal is carried from the nerve to the muscle by a chemical called acetylcholine. When acetylcholine reaches the muscle’s acetylcholine receptors, the muscle activates.
Once the muscle has been activated, acetylcholine needs to be removed from the area; otherwise, your muscle wouldn’t recognize the next signal coming through. This is taken care of by acetylcholinesterase, an enzyme that breaks down acetylcholine.
In the majority of patients with MG, the body’s immune system attacks the acetylcholine receptors, meaning that the action of acetylcholine is blocked. This disruption in communication between the nerve and the muscle is the cause of muscle weakness commonly experienced by patients with MG.
Cholinesterase inhibitors to the rescue
This jamming in the communication between nerves and muscles is the primary disease driver in MG. Because the body’s immune system is attacking acetylcholine receptors, we want acetylcholine to remain in the neuromuscular junction for as long as possible. This is because having higher levels of acetylcholine will increase the chance that it can bind to the remaining acetylcholine receptors that are still functional.
This is where acetylcholinesterase inhibitors come into the picture. Remember how the enzyme acetylcholinesterase breaks down acetylcholine? Acetylcholinesterase inhibitors prevent that from happening. This leads to increased levels of acetylcholine in the neuromuscular junction, which is what we want.
Acetylcholinesterase inhibitors such as pyridostigmine and neostigmine are thus a key tool for reducing symptoms in many patients with MG.
Read more about MG treatment and care
Do cholinesterase inhibitors help everyone with myasthenia gravis?
Unfortunately, no.
Myasthenia gravis is driven by different autoantibodies in different people. Cholinesterase inhibitors work best in those with anti-acetylcholine receptor antibodies (called AChR+ MG), which is about 80%-85% of patients.
In people with autoantibodies against muscle-specific kinase (MuSK), problems with the protein MuSK, not acetylcholine receptors, drive the disease. People with this form of MG generally respond poorly to cholinesterase inhibitors.
As with any therapy, cholinesterase inhibitors may not be the right fit for all patients; for example, some patients are bothered by side effects, such as abdominal cramps and blurred vision. If you have further questions about how cholinesterase inhibitors work, why they are prescribed or what your treatment options are, be sure to speak to your doctor during your next clinical visit.
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