A Comprehensive Monograph on Neostigmine (DB01400)

I. Introduction and Executive Summary

Preamble

Neostigmine is a parasympathomimetic agent that has served as a cornerstone of clinical practice in anesthesiology and neurology for nearly a century. As a synthetic small molecule, its primary pharmacological action is the reversible inhibition of the enzyme acetylcholinesterase (AChE).[1] This mechanism allows for the potentiation of acetylcholine at cholinergic synapses, a principle that has been harnessed for a range of therapeutic applications. The drug’s enduring presence in medicine is a testament to its reliable, predictable, and well-understood profile.

Historical Context

Patented in 1931 and receiving its initial U.S. Food and Drug Administration (FDA) approval in 1939, Neostigmine has a long and storied history of clinical use.[4] Its name is derived from the Greek

neos, meaning "new," and its design was inspired by the naturally occurring alkaloid physostigmine, representing an early triumph of rational drug design aimed at improving upon a natural prototype.[4]

Core Clinical Utility

The principal FDA-approved indication for Neostigmine is the reversal of the effects of non-depolarizing neuromuscular blocking agents (NMBAs) following surgery.[1] In this setting, it accelerates the recovery of muscle function, allowing for the safe return of spontaneous ventilation and airway reflexes. Beyond this primary role, Neostigmine has significant clinical applications, including the symptomatic treatment of myasthenia gravis, the management of acute colonic pseudo-obstruction (Ogilvie syndrome), and the treatment of postoperative and neurogenic urinary retention.[4]

Pharmacological Hallmark