cholinesterase inhibitor
A cholinesterase inhibitor boosts cholinergic signaling indirectly. Instead of imitating acetylcholine, it disables the enzyme that mops it up, so the body's own transmitter lingers in the synapse and acts longer and more strongly, much like jamming the cleanup crew so the message stays on the board.
The target enzyme is acetylcholinesterase, which normally breaks acetylcholine down within milliseconds. Reversible inhibitors such as neostigmine, pyridostigmine, and donepezil bind transiently; irreversible inhibitors such as organophosphates bind the enzyme almost permanently, which is why nerve agents and many insecticides are so toxic. Because they raise acetylcholine everywhere, their effects appear at muscarinic sites, nicotinic sites, and in the brain.
Therapeutic uses follow these sites: neostigmine and pyridostigmine strengthen muscle in myasthenia gravis and reverse non-depolarizing neuromuscular block, while centrally active donepezil and rivastigmine modestly help cognition in Alzheimer's disease. Overdose causes a cholinergic crisis treated with atropine and, for organophosphates, the enzyme reactivator pralidoxime.
Neostigmine is given at the end of surgery to reverse rocuronium, raising acetylcholine at the neuromuscular junction so muscle strength and breathing return.
Reversing a neuromuscular blocker after surgery.
Distinguishing a myasthenic crisis (too little acetylcholine, needs more drug) from a cholinergic crisis (too much, needs less) is critical, because both cause severe weakness yet require opposite treatments.