Description
Neostigmine is a cholinesterase inhibitor that contains a quaternary nitrogen atom, and as
a result it does not easily pass through the blood–brain barrier, thus having minimal toxicity on cholinesterase inhibition in the brain. The presence of a quaternary nitrogen atom
in the molecule leads to other significant differences between physostigmine and neostigmine, the main difference being that neostigmine, besides cholinesterase inhibition, has a
direct stimulatory effect on cholinergic receptors. However, with the exception of these
serious differences, the general action of neostigmine is analogous to the action of
physostigmine.
Uses
Like other reversible cholinesterase inhibitors, neostigmine exhibits powerful antimuscle relaxant action. This property of neostigmine is used in anesthesiology for
overcoming paralysis of skeletal muscle caused by muscle relaxants. Neostigmine is primarily used in myasthenia, motor damage after brain trauma, paralysis, for atrophy of the
optic nerve, and for treating atony of the bowels and urinary bladder.
Clinical Use
Myasthenia gravis
Antagonist to non-depolarising neuromuscular
blockade
Synthesis
Neostigmine, N,N,N-trimethyl-meta-(dimethylcarbomoyloxy)-phenylammonium methylsulfonate (13.2.9), which can be viewed as a simplified analog of
physostigmine, is made by reacting 3-dimethylaminophenol with N-dimethylcarbamoyl
chloride, which forms the dimethylcarbamate (13.2.8), and its subsequent alkylation using
dimethylsulfate forming the desired compound (13.2.9) [43].
Veterinary Drugs and Treatments
Neostigmine is indicated for rumen atony, initiating peristalsis,
emptying the bladder, and stimulating skeletal muscle contractions
in cattle, horses, sheep, and swine (Package insert; Stiglyn? 1:500-P/
M—Mallinckrodt). It has been used in the diagnosis and treatment
of myasthenia gravis and in treating non-depolarizing neuromuscular
blocking agents (curare-type) overdoses in dogs. Neostigmine
has also been used to treat massive ivermectin overdoses in cats.
Drug interactions
Potentially hazardous interactions with other drugs
Aminoglycosides, clindamycin and polymyxins
antagonise effects of neostigmine.
Metabolism
Poorly absorbed orally. Neostigmine undergoes hydrolysis
by cholinesterases and is also metabolised in the liver.
Neostigmine is rapidly eliminated and is excreted in the
urine both as unchanged drug and metabolites.
