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Drugs & neurotoxins

Uni of Notts, fundamentals of neuroscience, first year

TermDefinition
Mechanisms of action - loss of function (5) Blocking pores, competitive inhibitor, inhibiting opening mechanism, decreasing voltage sensitivity of proteins, inhibiting activation
Mechanism of action - gain of function (5) Enhancing effects of ligands, acting as an agonist, increasing voltage sensitivity of proteins, enhancing activation, inhibiting deactivation
Mode of action of Lidocaine Loses its charge to cross neuronal membrane then recharges to bind to VGSCs (Voltage Gated Sodium ion Channels) to promote inactivation from the inside
General anaesthetics & sedatives Binds to & agonises GABAa receptors to reduce neuronal excitability & hyperpolarise the cell, reducing the likelihood of an action potential propogation
Muscle relaxants Antagonises nACh receptors at neuromuscular junctions
Antiepileptics (anticonvulsants) Epilepsy is believed to be caused by lowered VGSC threshold. These drugs bind to VGSCs to enhance their inactivation properties & reduce mass excitability
Cardiac drugs Reduces cardiomyocyte contraction & dilates blood vessels by blocking VGCCs (Ca++ channels). Depolarisation still occurs the same, just leading to a smaller response & decaying faster
Neuroprotective drugs Ca++ can build up in neurones causing excitotoxicity which kills cells due to overexposure to glutamate at NMDA receptors (incomplete reuptake or leakage). These drugs block Ca++ channels in high voltage to prevent neurodegeneration
Use of neurotoxins in research (+example) Neurotoxins are specific to receptor types, allowing scientists to distinguish between them, purify, & dissect molecular elements. E.g., nicotine agonises ionotropic ACh whereas muscarine agonises metabotropic ACh channels
Use of neurotoxins in survival Animals & plants use them for self-defence or predation, targeting ion channels leads to very fast response
Use of neurotoxins by humans industrially Can be used as pesticides for crops or for specific medical therapies to alter the functioning of problematic channels. Even used in warfare e.g., sarin gas (ACh-esterase inhibitor)
How GABA receptors are classified Neurotoxin muscimol selectively binds to & agonises GABAa but not GABAb
Neurotoxins in column chromatography Since they selectively bind to specific proteins, they can be bound to beads in a column & have a solution containing the protein passed through which will bind strongly to the toxin. This is affinity chromatography
Example: Tetrodotoxin Has a high affinity for VGSC
Example: α-scorpion toxin Blocks inactivation gate of VGSC to cause a spastic paralysis of their prey
Example: d-tubocurarine Powerful competitive inhibitor of nACh causing fast paralysis, used as world's first ever muscle relaxant
Example: Batrachotoxin Lowers threshold of VGSCs to close to membrane resting potential while also inhibiting inactivation. Causes almost instant paralysis
Example: Zinconotide Analgesic peptide from cone snail blocking VGCCs preventing release of glutamate up to 1000x stronger than morphine without the dependence opioids can cause
Example: Neonicotinoids Agonise nACh receptors & can't be hydrolysed by acetylcholine esterase
Example: Cholinergic anthelminitics Agonists of nACh channels specific to nematodes
Example: Avermectins Agonise glutamate-gated chloride ion channels only in pests such as nematodes, tics, & lice causing hyperpolarisation paralysis
Neurotoxins as pesticides Early insecticides were toxic to non-pest animals & worked up the food chain to humans. Selective insecticides (e.g., pyrethroids from daisies) work like batrachotoxin except specific to insect VGCCs only
Created by: Beech47
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