the calabar river is found on the west coast of africa

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