INBDE Pharmacology Practice Test

Which class irreversibly inhibits acetylcholinesterase?

Organophosphates Reversible anticholinesterases Neostigmine Physostigmine

Correct Answer:

Physostigmine

Explanation:

Irreversible inhibition of acetylcholinesterase is caused by organophosphates. They permanently phosphorylate the serine in the enzyme’s active site, forming a covalent bond that is very slow to reverse. With time, aging of this phosphorylated complex makes reactivation essentially impossible, leading to prolonged acetylcholine signaling. In contrast, physostigmine is a reversible anticholinesterase (carbamate inhibitor); it temporarily blocks the enzyme, but the bond is hydrolyzed and enzyme activity returns. Neostigmine is also reversible. So the class that irreversibly inhibits acetylcholinesterase is organophosphates.

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