the calabar river is found on the west coast of africa
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The Calabar River is found on the West coast of Africa
The Calabar bean
The Calabar bean: An ordeal poisonThe 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
N
N
CH3
H
CH3
CH3
O
NH
O
CH3 ON+
CH3
CH3CH3
O
CH3
physostigmine acetyl choline
Nerve gases and insecticidesOrganophosphorus 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
CH3P
F
OO P OO
CN
NCH3P OO
S
N
CH3P
F
OO
Sarin Soman VX Tabun
Some common insecticides
OP
O
NO2
O
S
OP
SO
SOO
OO
OP
O N
N
O
S
O
O
NH
parathion malathion diazinon
carbaryl
Antidotes for nerve gasesAtropine 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
ON
O
N