Toxins targeting cholinergic transmission

Question 1

Pharmacognosy

Answer 1

The study of drugs from natural sources

Question 2

Plant Toxins

Answer 2

• some plants depend on animals for dispersal of their seeds, most find it an evolutionary advantage to deter insects and animals from eating their foliage
• Unpleasant tasting, or toxic substances

Question 3

Tobacco

Answer 3

• Nicotine is highly toxic to humans as it activates nAChR in autonomic ganglia
• Tobacco pickers can absorb enough through their skin
• lower doses, providing it can be delivered in a way that bypasses liver metabolism, it can have pleasurable/addictive effects in the CNS

Question 4

Laburnum

Answer 4

• The toxic principal in laburnum is cytisine
• This drug is a potent agonist at ganglionic nAChR and CNS subtypes
• not potent at muscle nAChR
• used as smoking cessation aid but is expensive
• alternatives are nicotine and varenicline

Question 5

Curare Alkaloids

Answer 5

• Strychnos toxifera
• Potent antagonist at muscle nAChR flaccid paralysis
  respiratory paralysis, death
• Once used as surgical NMJ blocker now superseded
• tubocurarine
• coat arrows and blow gun darts

Question 6

alkaloid

Answer 6

nitrogen containing compound of plant origin

Question 7

Tropane Alkaloids

Jimson weed

Answer 7

• Atropine, hyoscine (scopolamine)
  hyoscyamine
• Datura stramonium
• Both plants belong to the Solanaceae family, which also includes tobacco, potato, tomato and peppers
• This includes potatoes: green parts of the plant and the fruit contain solanine – toxic to humans

Question 8

Tropane Alkaloids

Deadly nightshade

Answer 8

• Atropine, hyoscine (scopolamine)
  hyoscyamine
• Atropa belladonna

Question 9

Atropine

Answer 9

‘Parasympatholytics’
Increased heart rate*
Dilated pupils
Dry mouth
Blurred vision

Question 10

Hyoscine

Answer 10

Balance problems
Hallucinations
Convulsions
Memory loss
motion sickness 
(depression, addiction, ‘truth drug’)

Question 11

Cholinesterase Inhibitors

Answer 11

- Chinese firmoss
Huperzine A
- Daffodils, snowdrops
Galantamine
- Calabar bean
Physostigmine

Question 12

Function of Cholinesterase Inhibitors

Answer 12

• poisoning with Calabar beans results in neuromuscular block (paralysis), seizures, loss of bladder and bowel control and eventually death by asphyxiation
• sarin is an irreversible inhibitor of AChE but physostigmine is reversible
• Calabar beans were used for trial by ordeal (aka the ‘ordeal bean’)

Question 13

Cholinesterase Inhibitors Therapeutic Applications

Answer 13

Physostigmine
- Myasthenia gravis
- Glaucoma
- Alzheimer’s Disease
Huperzine A
- Alzheimer’s Disease
Galantamine
- Alzheimer’s Disease

Question 14

Animal Toxins

Answer 14

Used in hunting of prey
Used to defend against predation
Paralysis/incapacitation of prey -> easier to eat
“Predigestion”

Question 15

Elapid Snake Toxins

Answer 15

Hollow-fanged snakes
Can inject large quantities of venom
Venom derived from saliva
Many different components (mostly peptides)
“predigestion”, cardiotoxins
neurotoxins

Question 16

Cobra Toxin

Answer 16

• alpha cobratoxin
• 71 aa peptide
• irreversible antagonist at NMJ nAChR - very potent
• Cobra toxin causes block of neuromuscular transmission, flaccid paralysis and death due to asphyxia

Question 17

Mamba Toxins

Answer 17

Dendrotoxins
Target K+ channels
Target mAChRs (M1, M4)

Question 18

Botulinum Toxin

Answer 18

Produced by bacterium Clostridium botulinum
Most deadly toxin known (human LD50 2 ng/kg)
Peptide toxin (seven different types)
Actually an enzyme.
- PREVENTS RELEASE OF ACH BY STOPPING SNARE PROTEINS
- The enzyme components of botulinum toxin are proteases. They cleave the SNARE proteins. This means that ACh cannot be released and results in a (frequently) fatal paralysis.