The history of acetylcholinesterase inhibitors in the treatment of myasthenia gravis

The beneficial effects of acetylcholinesterase inhibitors for the treatment of myasthenia gravis (MG) was a major discovery that came about through one young physician putting together a string of previous observations. To understand how this discovery came to light, we must first go back to earlier times when men hunted by bow-and-arrow to capture their prey. The substance used to poison the prey was eventually was identified as curare. Centuries later, a connection was made between the physiological effects of curare and a disease entity with no known pathological mechanism or treatment, myasthenia gravis. In 1935, house officer Dr. Mary Walker was the first physician to try physostigmine in the treatment of MG, which had previously been used to treat curare poisoning. What she saw was a dramatic improvement in the symptoms experienced in patients with MG, and thus became the first documented case of use of physostigmine, an acetylcholinesterase inhibitor, in the treatment of MG. This article is a summary of the history of the use of acetylcholinesterase inhibitors in the treatment of myasthenia gravis. This article is part of the special issue entitled ‘Acetylcholinesterase Inhibitors: From Bench to Bedside to Battlefield’. •Physostigmine was used to treat myasthenia gravis in 1934 by Dr. Mary Walker.•Patients with myasthenia gravis have symptoms similar to curare poisoning.•Physostigmine is a partial antagonist to curare.•Pyridostigmine, created in 1955, remains the mainstay of treatment for MG worldwide.•Edrophonium can be used to diagnose MG but is not available in the US.