Acetylcholine, cholinomimetic agents, cholinergic antagonists - Chronological milestones
In the early 1900s, release of compounds during stimulation of sympathetic and parasympathetic nerves was suspected (Langley, Dixon, Dale). This release was confirmed in 1921 by Otto Loewi who stimulated the vagus nerve of a frog heart perfused by a fluid which after came to perfuse a second heart frog. The frequency of beats of the first heart slowed down after the stimulation of the vagus but also, after a short time, the second heart slowed down. It was evident that a substance was liberated by the first heart. The substance responsible of this slowing was acetylcholine.
In the late 1850s, Claude Bernard showed that the locus of action of curare was between the nerve and the muscle.
Preparations of belladonna, Atropa belladona, are known since antiquity. Atropine was isolated from belladonna in 1831. The antagonist effect of atropine towards stimulation of parasympathetic nerve is known since 1870.
D-tubocurarine was introduced in anesthesiology around 1945.
Nicotine was isolated from tobacco in 1828.
Physostigmine or eserine, isolated from Calabar bean in 1864, was introduced in therapeutics in 1877.
Anticholinesterases with irreversible effect were synthesized around the years 1940.
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