throughout the 1860s by a few different Edinburgh scientists, including Douglas Argyll Robertson who wrote a paper on the use of Calabar bean extract on the eye and was the first to use it medicinally, and Thomas Richard Fraser, who researched how to best extract the active principle, which was later determined to be physostigmine. Fraser also studied the antagonism between physostigmine and atropine extremely rigorously, at a time when the concept of antagonism had little if any experimental support. Fraser's research is still the basis of today's knowledge about the interactions between atropine and physostigmine at many different and specific doses. Physostigmine's first use as a treatment for glaucoma was by Ludwig Laqueur in 1876. Laqueur himself had glaucoma so, like Christison, he experimented on himself, although Laqueur was much more scientific and methodical in his self-treatment. In the 1920s, Otto Loewi determined the biomechanical mechanism for the effects of physostigmine on the body. Loewi was studying how actions that we now consider to be controlled by the parasympathetic nervous system, were directed by chemicals. During his studies, Loewi discovered acetylcholine and that physostigmine acted by preventing acetylcholine inhibition. In 1936, Loewi was awarded the Nobel Prize for his work on discovering acetylcholine and biological chemical transmitters. More important discoveries surrounding physostigmine were made at the University of Edinburgh in 1925. Edgar Stedman and George Barger determined the structure of physostigmine using a method called chemical degradation. In 1935 Percy Lavon Julian was later the first to synthesize physostigmine. English scientist Robert Robinson was also working on the synthesis of physostigmine, but surprisingly Julian, a relatively unknown scientist at the time, was the successful one. In 1934, while working at St Alfege's Hospital in London, Dr Mary Walker discovered that a subcutaneous injection of physostigmine could temporarily reverse the muscle weakness found in patients with myasthenia gravis. She had noted that the symptoms and signs of myasthenia were similar to those found in curare poisoning, and physostigmine was used as an antidote to curare poisoning at that time. Her article explaining the first case of myasthenia gravis being successfully treated with physostigmine was published in The Lancet in June 1934. See also Neostigmine Miotine T-1123 TL-1238 References Acetylcholinesterase inhibitors Antidotes Alkaloids Aromatic carbamates Pyrroles Pyrroloindoles Secondary amines Alkaloids found in Fabaceae Plant toxins Ophthalmology drugs