Neostigmine is a cholinesterase inhibitor used in the symptomatic treatment of myasthenia gravis by improving muscle tone. Cholinergic neurons in the brain are primarily responsible for movement in skeletal muscles. In the neuron, acetylcholine is synthesized form acetyl-coa and choline, and stored into synaptic vesicles. When an action potential arrives at the nerve terminal, voltage gated calcium channels open leading to an influx of calcium ions into the neuron. This triggers the docking of the synaptic vesicle and release of acetylcholine into the synapse. Acetylcholine acts on nicotinic receptors on the motor end plate. Nicotinic receptors are cation channels, when activated they transport sodium ions into the motor end plate. The sodium causes depolarization of the cell, opening voltage gated calcium channels on the sarcoplasmic reticulum. Calcium enters the cytosol from the sarcoplasmic reticulum and binds to calmodulin. Calmodulin activates myosin light chain kinase. Myosin light chain kinase converts myosin light chain to phosphorylated myosin light chain. The phosphorylated myosin light chain causes actin to become bound to myosin leading to muscle contraction. The acetylcholine in the synapse is cleared rapidly by acetylcholinesterase which breaks acetylcholine down into choline and acetate. Choline is taken back up into the presynaptic neuron and recycled to produce more acetylcholine. Neostigmine reversibly inhibits the acetylcholinesterase enzyme, which normally breaks down acetylcholine. The main pharmacological actions of this drug are believed to occur as the result of this enzyme inhibition, enhancing cholinergic transmission, which improves muscle tone. Common side effects include bradyarrhythmias, bronchospasm, miosis, nausea, and increased peristalsis.

Neostigmine Pathway. References