Toxins targeting cholinergic transmission Flashcards
Pharmacognosy
The study of drugs from natural sources
Plant Toxins
- 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
Tobacco
- 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
Laburnum
- 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
Curare Alkaloids
- 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respiratory paralysis, death - Once used as surgical NMJ blocker now superseded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
alkaloid
nitrogen containing compound of plant origin
Tropane Alkaloids
Jimson weed
- 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
Tropane Alkaloids
Deadly nightshade
- Atropine, hyoscine (scopolamine)
hyoscyamine - Atropa belladonna
Atropine
‘Parasympatholytics’ Increased heart rate* Dilated pupils Dry mouth Blurred vision
Hyoscine
Balance problems Hallucinations Convulsions Memory loss motion sickness (depression, addiction, ‘truth drug’)
Cholinesterase Inhibitors
- Chinese firmoss Huperzine A - Daffodils, snowdrops Galantamine - Calabar bean Physostigmine
Function of Cholinesterase Inhibitors
- 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’)
Cholinesterase Inhibitors Therapeutic Applications
Physostigmine - Myasthenia gravis - Glaucoma - Alzheimer’s Disease Huperzine A - Alzheimer’s Disease Galantamine - Alzheimer’s Disease
Animal Toxins
Used in hunting of prey
Used to defend against predation
Paralysis/incapacitation of prey -> easier to eat
“Predigestion”
Elapid Snake Toxins
Hollow-fanged snakes Can inject large quantities of venom Venom derived from saliva Many different components (mostly peptides) “predigestion”, cardiotoxins neurotoxins
Cobra Toxin
- 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
Mamba Toxins
Dendrotoxins Target K+ channels Target mAChRs (M1, M4)
Botulinum Toxin
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.
