Which cholinesterase inhibitor can freely cross the blood-brain barrier?

The choice of physostigmine as the cholinesterase inhibitor that can freely cross the blood-brain barrier is accurate due to its chemical structure and properties. Physostigmine is a tertiary amine, which allows it to easily penetrate lipid membranes, including the blood-brain barrier, a selective barrier that protects the brain from certain substances in the bloodstream while allowing others that are lipophilic to pass through.

In contrast, neostigmine and pyridostigmine are quaternary ammonium compounds, which are largely hydrophilic. Their positive charge makes them less capable of crossing lipid membranes, including the blood-brain barrier, limiting their effects to peripheral cholinesterase inhibition. Edrophonium also lacks the necessary lipophilicity due to its quaternary structure, preventing it from crossing the barrier effectively.

Understanding these differences highlights the unique ability of physostigmine to influence central nervous system activity, making it valuable in treating conditions like glaucoma and reversing central anticholinergic toxicity.