Drugs and Poisons - Poisons

Aconitine

• Produced by plants in the Aconitum genus

• More commonly known as “wolfsbane”

• Used by Romans

Aconitine

• Locks sodium-ion channels in the open

conformation (agonist)

• Depolarizes membrane potential—nerves

cannot reset

• Death occurs due to cardiac arrest and/or

respiratory paralysis

Aconitine

Batrachotoxin

• Poison dart frogs (do not make toxin, bacteria or diet)

Batrachotoxin

Locks sodium-ion channels in the open conformation (agonist)

• Depolarizes membrane

potential—nerves cannot

reset

• Death occurs due to cardiac

arrest and/or respiratory

paralysis

• Frog ion channels have a

different structure that do

not bind the poison

Batrachotoxin

Coniine

Isolated from poison hemlock (Conium

maculatum) and Yellow Pitcher plant

• Used to execute Socrates (399 BCE)

Coniine

Locks sodium-ion channels in the open

conformation (agonist)

• Binds specifically to the sodium ion channels that

respond to acetylcholine or nicotine

• Death caused by asphyxia due to inability to breathe

Coniine

Tetrotodoxin

Tetrotodoxin

Isolated from many marine sources

• Pufferfish, octopi, squid & horseshoe crabs

• Also found in some flatworms and ringworms

• Produced by symbiotic bacteria

Tetrotodoxin

Blocks sodium ion channels (antagonist)

Nerves unable to signal—loss of feeling

Toxic doses cause paralysis of heart and

diaphragm

Sarin

Sarin

Developed by German chemist Gerhard

Schrader in 1938

 Based on a pesticide called Tabun (“taboo”)

 Utilized by Germany as a chemical weapon in WW2

 Also used during the 1988 Iran-Iraq war and 2013 Syrian Civil

War, as well as some domestic terror attacks in Japan

 Many related compounds include VX, Soman & Novichok

Sarin

Irreversible inhibitor of acetylcholine esterase

(AChE)

 Leads to a buildup of acetylcholine, causing

continuous neuron activation

 Death caused by asphyxia due to inability to control

the diaphragm

Ricin

Ricin

Isolated from Castor beans

 Ricinus communis

◼ A protein heterodimer consisting of two chains

(A & B) held together by a disulfide bond

 The A-chain (blue) is the active chain responsible for

toxicity

Ricin

A-chain cleaves adenine in 28S rRNA

 A structural component of the ribosome needed for

function (ribosomal RNA)

 One ricin A-chain can cleave these adenine residues

in 1500 ribosomes per minute

 Death occurs by shock and organ failure

Amatoxin

Amatoxin

Interferes with the movement of the “bridge helix” in RNA polymerase II

 Movement of the bridge is

required for translocation

 α-Amanitin binding reduces

nucleotide rate from several

thousand per minute to <10 per

minute

 Death occurs several days after

ingestion typically due to organ

and kidney failure

Amatoxin

Isolated from mushrooms, primarily those in the

genera Amanita, Galerina, and Lepiota

 Commonly known as “death cap” or “paddy straw”

 Many related compounds, depending on R groups

◼ α-Amanitin, β-Amanitin, γ-Amanitin etc.

◼ α-Amanitin most responsible for human deaths

Mustard Gas

Mustard Gas

First synthesized by several European

chemists in the late 1800’s

Exact dates are unclear

First utilized in war by Germany in WWI

Characteristic bullae (fluid-filled blisters)

Mustard Gas

• Initial effects are intense itching and blistering (chemical burns). Death occurs due to severe burn injuries.

• Alkylating properties make them strongly mutagenic and carcinogenic (can also cross-link DNA)

Zyklon B

Zyklon B

Cyanide-based pesticide

Hydrogen cyanide released once canister is

exposed to air

Used by Nazi Germany to execute Jews

starting early in 1942

Zyklon B

Binds the heme in cytochrome c oxidase

 Halts electron transport chain

 Acute exposure leads to cardiac arrest