A neurotoxin is a toxin that acts specifically on nerve cells (neurons), usually by interacting with membrane proteins such as ion channels. Some sources are more general, and define the effect of neurotoxins as occurring at nerve tissue. Bungarotoxin, which is considered a neurotoxin, has its effect at the motor end plate.
Toxins ingested from the environment are described as exogenous and include gases (such as carbon monoxide), metals (such as mercury), liquids (ethanol), and numerous solids. Many neurotoxins are found in plant and animal matter found in nature; for example the neurotoxin aesculin is found in the horse chestnut (Aesculus hippocastanum), and the California buckeye tree. When exogenous toxins are ingested, the effect on neurons is largely dependent on dosage.
Neurotoxicity also occurs from substances produced within the body, known as endogenous neurotoxins. An example of an endogenous neurotoxin is the primary neurotransmitter glutamate, which, when levels reach too high, can result in excitotoxicity and cause neuronal death by apoptosis.
Classification and examples
Many of the venoms and other toxins that organisms use in defense against predators are neurotoxins. A common effect is paralysis, which sets in very rapidly. The venom of bees, scorpions, pufferfish, spiders, and snakes can contain many different toxins.
Many neurotoxins act by affecting voltage-dependent ion channels:
Agent Channel tetrodotoxin and batrachotoxin sodium channels maurotoxin, agitoxin, charybdotoxin, margatoxin, slotoxin, scyllatoxin and hefutoxin potassium channels calciseptine, taicatoxin, calcicludine, and PhTx3 calcium channels
Saxitoxin is also a very potent natural neurotoxin, produced by some strains of marine dinoflagellates, cyanobacteria and puffer fish. Saxitoxins bioaccumulate in shellfish and certain finfish. Ingestion of saxitoxin, usually through shellfish contaminated by toxic algal blooms, can result in paralytic shellfish poisoning. Together with tetrodoxin, saxitoxin has been used in molecular biology to establish the function of the sodium channel. It acts on the voltage-gated sodium channels of nerve cells, preventing normal cellular function and leading to paralysis. The blocking of neuronal sodium channels which occurs in paralytic shellfish poisoning produces a flaccid paralysis that leaves its victim calm and conscious through the progression of symptoms. Death often occurs from respiratory failure.
Bungarotoxin is also a very potent neurotoxin. It binds irreversibly and competitively to the acetylcholine receptor found at the end plate of the neuromuscular junction, causing paralysis, and depending on the dose, can cause respiratory failure and death in the victim
Another very potent neurotoxin is taipoxin. The toxin causes a gradual reduction to complete stop of evoked and spontaneous release of acetylcholine from motor nerve terminals. If the dose is high enough, the victim can die from asphyxia caused by paralysis of the respiratory muscles.
Botulinum neurotoxins are the most potent natural toxins known(only tested on laboratory mice). They are produced by various toxigenic strains of Clostridium botulinum and act as metalloproteinases that enter peripheral cholinergic nerve terminals and cleave proteins that are crucial components of the neuroexocytosis apparatus, causing a persistent but reversible inhibition of neurotransmitter release resulting in flaccid muscle paralysis.
Examples of neurotoxic drugs include, but are not limited to:
- Certain psychostimulants, particularly methamphetamine and to a lesser degree dextroamphetamine and amphetamine, when used at high doses have been shown to cause dopaminergic and serotonergic neurotoxicity via oxidative stress. The neurotoxicity of stimulants such as cocaine and methylphenidate is debatable.
- Empathogen-entactogens such as MDMA and MDA (except MDAI) have been found to cause neurotoxicity to serotonergic nerve terminals, though this claim has been readily disputed.
- L-DOPA induces damage to striatal dopamine neurons, particularly after chronic usage. Also shown to potentiate neurotoxicity of amphetamines and other dopamine releasing agents
- NMDA receptor antagonists like ketamine, PCP, DXM, and dizocilpine (MK-801) have been shown to produce Olney's lesions in rodents, though this has never been observed in humans.
- GHB receptor agonists like GHB, GBL, and 1,4-BD, which damage the cerebral/prefrontal cortex and hippocampus via oxidative stress.
- NMDA receptor agonists like ibotenic acid (which is found in Amanita muscaria mushrooms) and GABA receptor antagonists like picrotoxin, and bicuculline are neurotoxic via excitotoxicity.
- Several antipsychotics have been linked to brain gray/white matter loss.
- Others such as 5,7-DHT, 6-OHDA, MPP+, MPTP, PBA, PCA, and PIA.
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Animal Poisons & Venoms: Batrachotoxin • Bestoxin • Birtoxin • Bungarotoxin • Charybdotoxin • Conotoxin • Saxitoxin • TetrodotoxinNeurotoxic drugs: Amphetamine • Lisdexamfetamine • Methamphetamine • αET • αMT • MBDB • MDA • MDEA • MDMA (Ecstasy) • PBA • PCA • PIA • 1,4-BD • GBL • GHB • Ibotenic Acid • Dizocilpine (MK-801) • Ketamine • Phencyclidine (PCP) • 5,7-DHT • 6-OHDA • MPTP/MPP+ • Norsalsolinol • Ethanol (Alcohol)
Bacterial toxins: Botulinum toxin • Tetanospasmin
Fungal toxins: Bicuculline
Plant toxins: Penitrem A • Picrotoxin
Nerve agents: Cyclosarin EA-3148 • GV (nerve agent) • Novichok agent • Sarin • Soman • Tabun (nerve agent) • VE (nerve agent) • VG (nerve agent) • VM (nerve agent) • VR (nerve agent) • VX (nerve agent)
Neurotransmitters and precursors: Dopamine • Glutamate • L-Tyrosine • L-Phenylalanine • L-DOPA (Levodopa) • L-Glutamine
Toxins (enterotoxin/neurotoxin/hemotoxin/cardiotoxin/phototoxin) Bacterial toxinsGram positiveCocciGram negative MycotoxinsAflatoxin · Amatoxin (alpha-amanitin, beta-amanitin, gamma-amanitin, epsilon-amanitin) · Citrinin · Cytochalasin · Ergotamine · Fumonisin (Fumonisin B1, Fumonisin B2) · Gliotoxin · Ibotenic acid · Muscimol · Ochratoxin · Patulin · Phalloidin · Sterigmatocystin · Trichothecene · Vomitoxin · Zeranol · Zearalenone Invertebrates Vertebratesreptile/snake venom: Bungarotoxin (Alpha-Bungarotoxin, Beta-Bungarotoxin) · Calciseptine · Taicatoxin · Calcicludine · Cardiotoxin IIInote: some toxins are produced by lower species and pass through intermediate species
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