The Calabar River is found on the
West coast of Africa
The Calabar bean
The Calabar bean: An ordeal poison
The growth of Calabar beans was controlled by
royalty.
People suspected of crimes were forced to eat a
Calabar bean.
If the suspect died, they were considered “guilty”.
If they vomited and survived, they were declared,
“not guilty”.
If they did not vomit and survived, the suspect
was still considered guilty and was sold into
slavery.
People accused of crimes often requested the
ordeal.
Symptoms of Calabar bean poisoning
Initially salivation and constriction of the pupils
of the eyes,
Followed by muscular contraction, vomiting and
diarrhea.
At first, respiration is increased.
Later, respiration slows.
Death is by respiratory or cardiac arrest.
Europeans discover Calabar beans
News of the ordeal poison reached Europe by the
1800's.
Explorers brought the plant to Scotland in 1855.
They grew but did not flower.
Preserved specimens with flowers arrived in
Scotland in 1859.
Professor Balfour named the plant, Physostigma
venenosum, in 1860.
What makes the Calabar bean so toxic?
Jobst and Hesse isolated an alkaloid from Calabar
beans in 1863, which they called
“physostigmine”.
Vee and Leven independently isolated an alkaloid
from Calabar beans in 1865, which they called,
“eserine”.
Physostigmine and eserine were found to be
identical compounds.
Physostigmine is the major toxic component of
Calabar beans.
What makes the Calabar bean so toxic?
Chemists began to investigate the biologically
active compounds in plants in the 1800s.
Most of these compounds were found to be
weakly basic, hence, “alkaloids”.
Indole alkaloids, made from tryptophan, are one
of the largest classes of alkaloids.
More than 1200 indole alkaloids are known.
Physostigimine inhibits the
breakdown of acetylcholine
Acetylcholine is a neurotransmitter at the
neuromuscular junction
Release of acetylcholine causes muscle
contraction
The acetylcholine is then hydrolyzed by an
enzyme, acetylcholinesterase, to release the
muscle
Physostigmine binds to acetylcholinesterase and
blocks the hydrolysis of acetylcholine
Physostigmine and Acetylcholine
O
H3C N
H
O
H3C
O
N
N
H
CH3
H3C
O
CH3
+ CH
3
N
CH3
CH3
physostigmine
acetyl choline
Nerve gases and insecticides
Organophosphorus compounds also are potent
inhibitors of acetylcholinesterase
These compounds have been used as nerve gases
in warfare
Similar compounds are also used as insecticides
These compounds react irreversibly with
acetylcholinesterase by attaching a phosphorus to
the enzyme
Nerve gases were used by Saddam Hussein in the
Iran war and against the Kurds
Sarin was used in a terroist attack by Aum
Shinrikyo in the Tokyo subway in 1995
Some nerve gases
CH3
O P O
F
Sarin
CH3
O P O
F
Soman
CH3
O P O
S
N
N
VX
O P O
CN
Tabun
Some common insecticides
NO2
S
O
P
O
O
S
O
P
O
O
O
S
S
O
O
parathion
P
O
N
O
N
O
diazinon
malathion
O
O
carbaryl
N
H
Antidotes for nerve gases
Atropine blocks the effect of acetylcholine, so it
can be used as an antidote for nerve gas poisoning
Atropine would be lethal if taken without nerve
gas exposure
Physostigmine can be taken prophylactically if
exposure to organophosphorus nerve agents is
anticipated
A synthetic analogue, pyridostigmine, was used
by the military in the 1st Gulf War
Pyridine-2-aldoxime methiodide (PAM) can
reactive acetylcholinesterase
Medical uses for physostigmine
Physostigmine is used for treatment of glaucoma
Since Alzheimer's disease is associated with
decreased acetylcholine in the brain,
physostigmine has been tested as an Alzheimer's
treatment
Physostigmine was not effective for Alzheimer's
A synthetic analogue, rivastigmine, has shown
some efficacy in treatment of Alzheimer's and
Parkinson's disease
Rivastigmine
O
N
O
N