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Neostigmine is a cholinesterase inhibitor used primarily for the treatment of myasthenia gravis, as well as for the reversal of neuromuscular paralysis. It works by inhibiting the reuptake of acetylcholine, thereby increasing the amount of acetylcholine in the junction. Neostigmine works only in the periphery though, and cannot cross the blood-brain barrier and therefore cannot enter the CNS. Note that increased acetylcholine levels can cause signs of cholinergic overload.

Key Points

  • Neostigmine
    • Mechanism
      • (Acetyl)cholinesterase inhibitor increases acetylcholine
        • Works peripherally (cannot cross BBB)
          • Neostigmine’s polarity is too high to cross the BBB
    • Clinical Use
      • Myasthenia gravis treatment
      • Neuromuscular junction blockade reversal
        • Must be given with atropine to prevent muscarinic effects such as bradycardia
      • Postoperative and neurogenic ileus and urinary retention
    • Physostigmine > neostigmine as antidote for anticholinergic activity
      • Physostigmine enters the CNS, whereas neostigmine does not cross the BBB
        • Neostigmine therefore can’t treat CNS effects of anticholinergic toxicity (e.g. delirium, agitation)
    • Adverse Effects
      • Cholinergic overstimulation (the usual laundry list)
        • DUMBELLS (this is a bad mnemonic that’s unfortunately canon)
          • Diarrhea, Urination, Miosis, Bradycardia, Emesis, Lacrimation, Lethargy, and Salivation
        • Treatment of adverse effects
          • Atropine: blocks muscarinic receptors
          • Pralidoxime: regenerates acetylcholinesterase (AChE)