Neostigmine

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.

Raw materials

Preparation Products