HI I’m Dr Simon Freilich Consultant in Clinical Neurophysiology
In this video I’m going to explain how nerve agents work with specific regard to the recent
Skripal Poisoning. For those of you who don’t follow
my channel, I am not a toxicologist, pharmacologist, intensive care physician or warfare expert.
But I do know at least some neurophysiology and this is a
very relevant topic for us. Nerve agents come from a chemical family called
organophosphates. These were initially developed as pesticides in the 1930’s but given their
potential for toxicity, these were developed into agents of
chemical warfare. As the first group of these were developed
in Germany, they were given the term G-series and
include, Sarin, Cyclosarin, Tabun etc. Use of these included the Tokyo Metro Sarin attack
and of course, most recently in Syria with devastating effects.
because they were inherently unstable, successors were sought, and the even more lethal V-series
was born in the 1950’s with VM, VX and VR. Kim Jong Un’s half brother was infamously
assassinated with an oil based form of VX.
Russia in the 1980’s and 90’s then developed an even more deadly series which are classed
as Novichok but which little is known about.
Fortunately, we do at least know that their common physiological target is an enzyme called
Acetylcholinesterase. One of the bodies most important neurotransmitters
is Acetyl-Choline. It is found both in the Central
Nervous System and the Peripheral Nervous System and transmits signal at specific receptors
called Nictonic and Muscarinic receptors.
Once this transmitter has been released, the body recycles it using an enzyme called Acetly-
Cholinesterase. Organophosphates bind to this enzyme and block it from recycling the Acetyl-
Choline. As a result the levels of released Acetyl-Choline rise and lead to increased
and persistent signalling.
This leads to widespread and fairly characteristic signs
Muscarinic overactivation leads to copious tearing, pinpoint pupils, hypersalivation
and sweating. The airway muscles constrict and make it harder
to breath and to fill up with fluid. The heart slows
down and gut hypermotility leads to stomach cramps, vomiting and diarrhoea.
Nicotinic overactivation occurs
at higher doses
and leads to overstimulation