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Small molecule
PubChem CID 4991

Pyridostigmine

Mestinon
Mechanism of action
Acetylcholinesterase
In plain language
Blocks the enzyme that breaks down a nerve-signaling chemical, so more of it lingers at the junction between nerves and muscles, helping weak muscles contract better.
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How it works
Pyridostigmine reversibly inhibits acetylcholinesterase, the enzyme that normally hydrolyzes acetylcholine at cholinergic synapses, thereby slowing acetylcholine breakdown and permitting freer transmission of nerve impulses across the neuromuscular junction. In myasthenia gravis, autoantibodies reduce the number of functional postsynaptic nicotinic acetylcholine at the neuromuscular junction, lowering the safety margin for transmission and producing fluctuating skeletal muscle weakness and fatigability; by prolonging acetylcholine's presence in the synaptic cleft, pyridostigmine partially compensates for this receptor deficit and improves muscle strength. The manufacturer's label describes pyridostigmine as an of neostigmine, differing in having a longer duration of action and fewer gastrointestinal side effects. Because its effect depends on dosing relative to disease severity, both underdosing and overdosing can worsen muscle weakness, so treatment requires individualized titration and monitoring to distinguish myasthenic worsening from cholinergic excess.
Therapeutic applications
Indicated for the treatment of myasthenia gravis, a chronic autoimmune neuromuscular disorder in which impair signal transmission at the neuromuscular junction, producing fluctuating skeletal muscle weakness and abnormal fatigability that characteristically worsens with sustained activity and improves with rest. As a reversible cholinesterase inhibitor, pyridostigmine is used to control myasthenic symptoms and improve muscle strength, including ocular, bulbar (speech, swallowing), limb, and respiratory muscle involvement, and can be used long-term as maintenance therapy. Dosage must be individualized to the patient's symptom pattern and severity, since both undertreatment and overtreatment can produce muscle weakness — the label specifically distinguishes this from myasthenic crisis versus cholinergic crisis, a critical distinction given that increasing the dose in the presence of cholinergic crisis can have serious consequences.
Class
Therapeutic area
Neuromuscular
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