A Bit of History on Physostigmine and Its Use in Prague

Overview

In the 1860s, the extract of the Calabar bean or Esére nutwasstudied as a poison butwasalso introduced into ophthalmologyas an antagonist for atropine. Kleinwächter in Prague described it in 1864 as a succesful and specific antidote for atropinepoisoning. Several decades passed before physostigmine was isolated, but this substance has remained famous becauseit enabled discovery and establishment of neurotransmission, which started with the discovery of muscarinic action ofacetylcholine. The anti-curare properties of physostigmine were demonstrated in 1900 by Pal. However, when curare was atlast introduced into clinical anaesthesia in 1942, the antagonist used became the synthetic neostigmine. In the 1960s and1970s, physostigmine played a crucial role in reversal of anticholinergic effects of drugs in psychiatry, toxicology and lateron, during recovery from anaesthesia. The complex behavioural central anticholinergic syndrome (CAS) was described byLongo. Nowadays, physostigmine remains a safe and quite unique agent wherever increase of acetylcholine in the brain isnecessary, examples being intoxications with anticholinergic drugs, recovery from anaesthesia and in psychiatry. Physostigmineis being investigated not only for its role in alleviating symptoms of Alzheimer’s disease, but also for its capacityto counteract opiate-induced respiratory depression without abolishing analgesia. Eseroline, the first metabolite ofphysostigmine, is being investigated for its opioid-like and cholinesterase-inhibiting properties. Effects of physostigmineapplied into cerebrospinal fluid will probably be studied soon.

Key words:
physostigmine – atropine antidote – Central Anticholinergic Syndrome – intoxications – central muscarinictransmission – anaesthesia