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what are alkaloids?
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what are the two main classes?
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how are alkaloids synthesised?
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a basic organic compound containing nitrogen
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heterocyclic
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from the amino acids phenylalanine, tryptophan, and tyrosine
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non-heterocyclic
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where are cholinergic receptors found?
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what is the primary ligand for the cholinergic receptor?
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how does it function as a neurotransmitter?
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what are the two main types of cholinergic receptors?
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does it have a faster or slower response?
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central nervous system
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acetylcholine
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it opens ligand-gated ion channels
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ionotropic receptors (direct neurotransmitter action)
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faster
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autonomic nervous system (regulates homeostasis)
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metabotropic receptors (indirect neurotransmitter action)
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slower
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musculoskeletal system
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what are the two classes of cholinergic receptors?
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what kind of receptors are they?
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does it have a faster or slower response?
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what are the main types of these receptors?
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where are they found?
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nicotinic acetylcholine receptors
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ion channel-linked receptors
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faster (direct channel opening)
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N1
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skeletal muscle (neuromuscular)
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N2
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neuronal receptors (nerve synapses)
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muscarinic acetylcholine receptors
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G protein-coupled receptors
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slower (act via secondary messengers)
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M1
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gastric secretions, CNS
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M2
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heart muscle (contraction)
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M3
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glands (e.g. salivary, pancreas)
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M4 & M5
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central nervous system
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what is nicotine?
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what is the mechanism of action of nicotine?
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how can this lead to a toxic effect?
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what are the physiological consequences of nicotine toxicity?
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what is the LD50 of nicotine?
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a parasympathomimetic alkaloid found in the Solanaceae (nightshade) family of plants
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it binds to the nicotinic receptors in the CNS & acts as a 'volume control'
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through excessive stimulations of the nicotinic acetylcholine receptors
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initial symptoms: nausea, vomiting, hypertension, tachycardia, dizziness, and seizure
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0.5 to 1.0mg/kg for adults
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it increases release of neurotransmitters, providing a stimulant effect
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it also interacts with nicotinic receptors in the adrenal gland, stimulating the release of adrenaline
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after excessive stimulation, receptor levels are depressed
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subsequent symptoms: hypotension, bradycardia, CNS depression, coma, and paralysis
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what is muscarine?
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what is the mechanism of action of muscarine?
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how can this lead to a toxic effect?
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what are the physiological consequences of muscarine toxicity?
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what is the LD50 of muscarine?
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an alkaloid found in many species of mushroom
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it binds to the muscarinic receptors and activates them (same as ACh)
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through excessive activation of the muscarinic acetylcholine receptors
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cardiac arrest via M2 receptors (through bradycardia & low blood pressure)
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unknown in humans (0.23mg/kg in mice)
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convulsion and hypothermia via M1, M4, and M5 receptors in the brain
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bronchoconstriction and severe gastrointestinal symptoms
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what is glycine?
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what is its function in the CNS?
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where are glycine receptors (GlyRs) found?
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what kind of receptor is the GlyR?
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what does it do?
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the smallest of the 20 common amino acids (MW: 75 Da)
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an inhibitory neurotransmitter
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in the CNS (especially in the brain cord, brain stem, and retina)
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ionotropic receptor
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regulates chloride movement
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when the receptor is activated, chloride enters the neuron
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an essential precursor in the synthesis of porphyrins (most important porphyrin in haem)
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this creates an inhibitory post-synaptic potential, making the neuron less likely to generate an action potential
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what is strychnine?
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what is the mechanism of action of strychnine?
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how can this lead to a toxic effect?
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what are the physiological consequences of strychnine toxicity?
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what is the LD50 of strychnine?
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an alkaloid found in the seeds of the Strychnos tree (one of the most bitter chemicals known)
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it acts as an antagonist, and prevents glycine from binding to GlyR
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without the glycine inhibiting GlyR, the nervous system becomes hypersensitive
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initial symptoms include restlessness, muscle twitching, and stiffness of the neck
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1-2mg/kg in humans
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action potentials are triggered by very low levels of neurotransmitter, causing constant muscle contractions/twitching
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later symptoms include convulsions and dilation of the pupils
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death usually occurs as a result of respiratory arrest and asphyxia
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what is ricin?
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what is the mechanism of action of ricin?
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how can this lead to a toxic effect?
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what are the physiological consequences of ricin toxicity?
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what is the LD50 of ricin?
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a lectin (carbohydrate-binding protein) from the seeds of the castor oil plant
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it is a type 2 ribosome-inactivating protein (RIP) or holotoxin (a single ricin molecule can inactivate 1500 ribosomes per minute)
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it irreversibly hydrolyses a glycosidic bond in the rRNA of the 60s ribosomal subunit
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severe diarrhea
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22ug/kg from injection or inhalation (approx 1.8mg/adult - 20 castor seeds could kill an adult)
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this rapidly and completely inactivates the ribosome
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death usually occurs from circulatory shock due to a shutdown of metabolism
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this shuts down protein synthesis within the cells
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