Myasthenia gravis is a rare autoimmune
neuromuscular junction disorder mainly caused by
antibodies being targeted against the muscle
acetylcholine receptors (AChRs). The loss of AChRs leads to a defect in neuromuscular transmission resulting in
muscle weakness and
fatigue. Although once an often fatal illness,
Myasthenia gravis can now be well managed with relatively safe and effective treatments. However, the severe myasthenic cases associated with
thymus tumors remain often fatal exception in the management of the disease. The early treatment includes the use of
acetylcholinesterase inhibitors (AChEI) which enhance neuromuscular transmission. To ensure a peripheral effect, charged molecules are used, particularly quaternary
ammonium salts. The structure of AChEIs has been continuously modified to obtain the optimal ratio between AChE inhibition and potential side-effects. This review summarizes progress in the use of quaternary compounds as AChE inhibitors in vitro with respect to their structure and inhibitory ability. Namely,
carbamic acid esters, piperidinium and pyridinium
salts, bisquaternary pyridinium
salts and heterogeneous quaternary inhibitors are all discussed. Among data found in the literature, many compounds have shown promising inhibition of AChE when compared to commercial standards (
pyridostigmine,
neostigmine). Besides a promising inhibitory ability, selectivity for AChE versus
butyrylcholinesterase (BChE) for the most potent compounds (sub-nanomolar IC(50)) was also identified.