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In the 1860s, the extract of the Calabar bean or Esere nut was studied as a poison but was also introduced into ophthalmology as an antagonist for atropine. Kleinwachter of Prague described it in 1864 as a successful and specific antidote for atropine poisoning. Several decades passed before physostigmine was isolated, but this substance has remained famous because it enabled discovery and establishment of neurotransmission which started with the discovery of mucarinic action of acetylcholine. The anti-curare properties of physostigmine were demonstrated in 1900 by Pal. However, when curare was at long last introduced into clinical anaesthesia in 1942, the antagonist used became the synthetic neostigmine. In the 1960s and 1970s, physostigmine played a crucial role in reversal of anticholinergic effects of drugs in psychiatry, toxicology and, later on, during recovery from anaesthesia. The complex behavioural central anticholinergic syndrome (CAS) was described by Longo. Nowadays, physostigmine remains a safe and quite unique agent wherever increase of acetylcholine in the brain is necessary, examples being intoxications with anticholinergic drugs, recovery from anaesthesia and in psychiatry. Physostigmine is being investigated not only for its role in alleviating symptoms of Alzheimer's disease, but also for its capacity to counteract opiate-induced respiratory depression without abolishing analgesia. Eseroline, the first metabolite of physostigmine, is being investigated for its opioid-like and cholinesterase-inhibiting properties. Effects of physostigmine applied into spinal liquor will probably be studied soon. |
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