Acetylcholinesterase inhibitors in MG: to be or not to be?
Myasthenia gravis (MG) is an autoimmune disorder usually caused by antibodies against either the acetylcholine receptor (AChR) or muscle-specific tyrosine kinase (MuSK) at the neuromuscular junction. Neuromuscular transmission failure results in muscle fatigue and weakness that can be treated symptomatically with acetylcholinesterase inhibitors (AChEIs). Long-term treatment with nonselective AChEIs may have considerable drawbacks; thus, this medication is ideally tapered when strength improves. Patients with AChR antibodies respond beneficially to treatment, whereas patients with MuSK antibodies generally do not. Recently, the selective AChEI EN101, which specifically targets the isoform of "read-through" AChE (AChE-R), has been developed and may be of importance for symptomatic relief in AChR-antibody seropositive MG. This article is a review of the mechanisms, therapeutic effects, and drawbacks, with both old and new AChEIs in MG.
Punga
Anna Rostedt
AR
Department of Clinical Neurophysiology, Uppsala University Hospital, 75185 Uppsala, Sweden. annarostedtpunga@gmail.com
Stålberg
Erik
E
D000109:Acetylcholine / Q000378:metabolism; D000110:Acetylcholinesterase / Q000737:chemistry / Q000187:drug effects / Q000235:genetics; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use; D007165:Immunosuppression Therapy / Q000379:methods; D009157:Myasthenia Gravis / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D009469:Neuromuscular Junction / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology / Q000627:therapeutic use; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D002800:Cholinesterase Inhibitors; C477243:EN101; D007155:Immunologic Factors; D009838:Oligodeoxyribonucleotides; D011950:Receptors, Cholinergic; D000110:Acetylcholinesterase; D000109:Acetylcholine