A monoamine neurotoxin, or monoaminergic neurotoxin, is a

drug A drug is any chemical substance other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect. Consumption of drugs can be via insufflation (medicine), inhalation, drug i ...

that selectively damages or destroys

monoaminergic Monoaminergic means "working on monoamine neurotransmitters", which include serotonin, dopamine, norepinephrine, epinephrine, and histamine. A monoaminergic, or monoaminergic drug, is a chemical, which functions to directly modulate the seroton ...

neuron A neuron (American English), neurone (British English), or nerve cell, is an membrane potential#Cell excitability, excitable cell (biology), cell that fires electric signals called action potentials across a neural network (biology), neural net ...

s. Monoaminergic neurons are neurons that signal via stimulation by

monoamine neurotransmitter Monoamine neurotransmitters are neurotransmitters and neuromodulators that contain one amino group connected to an aromatic ring by a two-carbon chain (such as -CH2-CH2-). Examples are dopamine, norepinephrine and serotonin. All monoamines ...

s including

serotonin Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. It is an amine synthesized ...

, and

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic compound, organic chemical in the catecholamine family that functions in the brain and human body, body as a hormone, neurotransmitter and neuromodulator. The ...

. Examples of monoamine neurotoxins include the serotonergic neurotoxins ''para''-chloroamphetamine (PCA),

methylenedioxymethamphetamine 3,4-Methylenedioxymethamphetamine (MDMA), commonly known as ecstasy (tablet form), and molly (crystal form), is an empathogen–entactogenic drug with stimulant and minor psychedelic properties. In studies, it has been used alongside psych ...

(MDMA), and 5,7-dihydroxytryptamine (5,7-DHT); the

dopaminergic Dopaminergic means "related to dopamine" (literally, "working on dopamine"), a common neurotransmitter. Dopaminergic substances or actions increase dopamine-related activity in the brain. Dopaminergic pathways, Dopaminergic brain pathways facil ...

neurotoxins oxidopamine (6-hydroxydopamine),

MPTP MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is an organic compound. It is classified as a tetrahydropyridine. It is of interest as a precursor to the monoaminergic neurotoxin MPP+, which causes permanent symptoms of Parkinson's dise ...

, and

methamphetamine Methamphetamine (contracted from ) is a potent central nervous system (CNS) stimulant that is mainly used as a recreational drug use, recreational or Performance-enhancing substance, performance-enhancing drug and less commonly as a secon ...

; and the noradrenergic neurotoxins oxidopamine and DSP-4. In the case of serotonergic neurotoxins like MDMA, research suggests that simultaneous induction of serotonin and dopamine release, serotonin depletion, dopamine uptake and

metabolism Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the co ...

hyperthermia Hyperthermia, also known as overheating, is a condition in which an individual's body temperature is elevated beyond normal due to failed thermoregulation. The person's body produces or absorbs more heat than it dissipates. When extreme te ...

oxidative stress Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal ...

and

antioxidant Antioxidants are Chemical compound, compounds that inhibit Redox, oxidation, a chemical reaction that can produce Radical (chemistry), free radicals. Autoxidation leads to degradation of organic compounds, including living matter. Antioxidants ...

depletion, and/or drug

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

s may all be involved in the neurotoxicity. On the other hand, there is evidence that drug metabolites may not be involved. Some research suggests that serotonergic neurotoxicity might represent neuroadaptive mechanisms rather than neuronal damage ''per se''. Dopaminergic neurotoxins can induce a

Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a neurodegenerative disease primarily of the central nervous system, affecting both motor system, motor and non-motor systems. Symptoms typically develop gradually and non-motor issues become ...

-like condition in animals and humans. Serotonergic neurotoxins have been associated with

cognitive Cognition is the "mental action or process of acquiring knowledge and understanding through thought, experience, and the senses". It encompasses all aspects of intellectual functions and processes such as: perception, attention, thought, ...

and memory deficits and psychiatric changes.

List of monoamine neurotoxins

Serotonergic neurotoxins

Phenethylamines

* 2,4-Dichloroamphetamine (2,4-DCA) *

2,4,5-Trihydroxyamphetamine 2,4,5-Trihydroxyamphetamine (THA) is a neurotoxin and a metabolite of MDMA. It comes from the ring-hydroxylation of 3,4-methylenedioxyamphetamine (MDA). In one paper, it was shown to reduce hippocampal tryptophan hydroxylase activity by 54% afte ...

(2,4,5-THA) *

2,4,5-Trihydroxymethamphetamine 2,4,5-Trihydroxymethamphetamine (THMA or THM) is a neurotoxin and a metabolite of MDMA. It has structural similarity to the dopamine neurotoxin 6-hydroxydopamine, and produces lasting serotonin deficits when administered centrally. See also * 2,4 ...

(2,4,5-THMA) * 3-Chloroamphetamine (3-CA) * 3,4-Dichloroamphetamine (3,4-DCA) * 3,4-Dihydroxyamphetamine (HHA; 3,4-DHA; α-methyldopamine; α-Me-DA) *

3,4-Dihydroxymethamphetamine 3,4-Dihydroxymethamphetamine (HHMA, 3,4-DHMA), or 3,4-dihydroxy-''N''-methylamphetamine, also known as α-methylepinine or α,''N''-dimethyldopamine, is the major metabolite of 3,4-methylenedioxy-''N''-methylamphetamine (MDMA). It is formed fro ...

(HHMA; 3,4-DHMA; α-methylepinine; α,''N''-dimethyldopamine) * 3,4-Methylenedioxyamphetamine (MDA) * 3,4-Methylenedioxyethylamphetamine (MDEA) * 3,4-Methylenedioxymethamphetamine (MDMA) * 4-Chlorophenylisobutylamine (4-CAB; 4-chloro-α-desmethyl-α-ethylamphetamine; α-ethyl-PCA) * 5-MAPB *

Fenfluramine Fenfluramine, sold under the brand name Fintepla, is a serotonergic medication used for the treatment of seizures associated with Dravet syndrome and Lennox–Gastaut syndrome. It was formerly used as an appetite suppressant in the treat ...

* Mephedrone *

Methamphetamine Methamphetamine (contracted from ) is a potent central nervous system (CNS) stimulant that is mainly used as a recreational drug use, recreational or Performance-enhancing substance, performance-enhancing drug and less commonly as a secon ...

Methylbenzodioxolylbutanamine MBDB, also known as ''N''-methyl-1,3-benzodioxolylbutanamine or as 3,4-methylenedioxy-''N''-methyl-α-ethylphenylethylamine, is an entactogen of the phenethylamine, amphetamine, and phenylisobutylamine families related to MDMA. It is known by th ...

(MBDB) *

Methylone Methylone, also known as 3,4-methylenedioxy-''N''-methylcathinone (MDMC), is an entactogen and stimulant drug of the amphetamine, cathinone, and benzodioxole families related to 3,4-methylenedioxymethamphetamine (MDMA; "ecstasy"). It is th ...

* Norfenfluramine * ''para''-Bromoamphetamine (PBA; 4-bromoamphetamine; 4-BA) * ''para''-Bromomethamphetamine (PBMA; 4-bromomethamphetamine; 4-BMA) * ''para''-Chloroamphetamine (PCA; 4-chloroamphetamine; 4-CA) * ''para''-Chloromethamphetamine (PCMA; 4-chloromethamphetamine; 4-PCMA) * ''para''-Iodoamphetamine (PIA; 4-iodoamphetamine; 4-IA)

Tryptamines

* 4-Hydroxy-5-methoxytryptamine (4-HO-5-MeO-T) * 4,5-Dihydroxytryptamine (4,5-DHT) * 5,6-Dihydroxytryptamine (5,6-DHT) * 5,7-Dihydroxytryptamine (5,7-DHT) * 6,7-Dihydroxytryptamine (6,7-DHT) *

α-Ethyltryptamine α-Ethyltryptamine (αET, AET), also known as etryptamine, is an entactogen and stimulant drug of the tryptamine family. It was originally developed and marketed as an antidepressant under the brand name Monase by Upjohn in the 1960s before bei ...

(αET)

2-Aminoindans

* 5-Iodo-2-aminoindan (5-IAI) (weak) * 5-Methoxy-6-methyl-2-aminoindane (MMAI) (weak; alone and with

amphetamine Amphetamine (contracted from Alpha and beta carbon, alpha-methylphenethylamine, methylphenethylamine) is a central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, an ...

) * 5,6-Methylenedioxy-2-aminoindan (MDAI) (weak; alone and with amphetamine)

MPTP-related

* 2′-NH₂-MPTP (2′-amino-MPTP) *

Haloperidol Haloperidol, sold under the brand name Haldol among others, is a typical antipsychotic medication. Haloperidol is used in the treatment of schizophrenia, tics in Tourette syndrome, mania in bipolar disorder, delirium, agitation, acute psychos ...

* HPP⁺ (haloperidol pyridinium) * HPTP

Dopaminergic neurotoxins

Phenethylamines

(2,4,5-THA) *

(2,4,5-THMA) * 3,4-Methylenedioxymethamphetamine (MDMA) (in mice but not in humans) * 4-Methylmethamphetamine (4-MMA; mephedrine) * 6-Hydroxydopa (6-OH-DOPA, 6-OHDOPA) * 6-Hydroxydopamine quinone (6-OHDA quinone; oxidopamine quinone) *

Amphetamine Amphetamine (contracted from Alpha and beta carbon, alpha-methylphenethylamine, methylphenethylamine) is a central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, an ...

* Mephedrone *

* Methcathinone *

* Oxidopamine (6-hydroxydopamine; 6-OHDA)

=Dopamine and metabolites

= * 3,4-Dihydroxyphenylacetaldehyde (DOPAL; dopamine aldehyde) * 5-''S''-Cysteinyldopamine (5-''S''-CyS-DA) * DOPA quinone * DOPAL quinone *

Dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. It is an amine synthesized ...

* Dopamine quinone * ''N''-Methylnorsalsolinol * Norsalsolinol * Salsolinol

Tryptamines

* 5,6-Dihydroxytryptamine (5,6-DHT) * 6,7-Dihydroxytryptamine (6,7-DHT)

MPTP-related

* 2′-CH₃-MPTP (2′-methyl-MPTP) *

* HPP⁺ (haloperidol pyridinium) * HPTP * MPP⁺ (cyperquat) *

Pesticides

Benomyl Benomyl (also marketed as Benlate) is a fungicide introduced in 1968 by DuPont. It is a systemic benzimidazole fungicide that is selectively toxic to microorganisms and invertebrates (especially earthworms), but relatively nontoxic toward mammals. ...

* Daidzin *

Dieldrin Dieldrin is an organochlorine compound originally produced in 1948 by J. Hyman & Co, Denver, as an insecticide. Dieldrin is closely related to aldrin, which reacts further to form dieldrin. Aldrin is not toxic to insects; it is oxidized in the i ...

* Fenpropathrin *

Mancozeb Mancozeb is a dithiocarbamate non-systemic agricultural fungicide with multi-site, protective action on contact. It is a combination of two other dithiocarbamates: maneb and zineb. The mixture controls many fungal diseases in a wide range of fi ...

Maneb Maneb (manganese ethylene-bis-dithiocarbamate) is a fungicide and a polymeric complex of manganese with the ethylene bis (dithiocarbamate) anionic ligand. Health effects Exposure to maneb can occur when breathed in; it can irritate the eyes, ...

Paraquat Paraquat ( trivial name; ), or ''N'',''N''′-dimethyl-4,4′-bipyridinium dichloride (systematic name), also known as methyl viologen, is a toxic organic compound with the chemical formula C6H7N)2l2. It is classified as a viologen, a family o ...

Rotenone Rotenone is an odorless, colorless, crystalline isoflavone. It occurs naturally in the seeds and stems of several plants, such as the jicama vine, and in the roots of several other members of the Fabaceae. It was the first-described member of the ...

Ziram Zinc dimethyldithiocarbamate is a coordination complex of zinc with dimethyldithiocarbamate. It is a pale yellow solid that is used as a fungicide, the sulfur vulcanization of rubber, and other industrial applications. Applications Known as ziram ...

Others

* Aldehyde dehydrogenase (ALDH) inhibitors (e.g.,

disulfiram Disulfiram is a medication used to support the treatment of chronic alcoholism by producing an acute sensitivity to ethanol (drinking alcohol). Disulfiram works by Enzyme inhibition, inhibiting the enzyme aldehyde dehydrogenase (specifically ALD ...

methylmercury Methylmercury is an organometallic cation with the formula . It is the simplest organomercury compound. Methylmercury is extremely toxic, and its derivatives are the major source of organic mercury for humans. It is a bioaccumulative environment ...

)

Noradrenergic neurotoxins

Phenethylamines and related

(2,4,5-THA) * 3,4-Methylenedioxyamphetamine (MDA) * 3,4-Dihydroxyphenylglycolaldehyde (DOPEGAL; norepinephrine/epinephrine aldehyde) * 6-Hydroxydopa (6-OH-DOPA, 6-OHDOPA) * DSP-4 * Oxidopamine (6-hydroxydopamine; 6-OHDA) * Xylamine

Tryptamines and related

* 4,5-Dihydroxytryptamine (4,5-DHT) * 5,6-Dihydroxytryptamine (5,6-DHT) * 5,7-Dihydroxytryptamine (5,7-DHT)

MPTP-related

* 2′-NH₂-MPTP (2′-amino-MPTP)

Unsorted or unknown

* 5-Hydroxyindoleacetaldehyde (5-HIAL) * RHPP⁺ * RHPTP

References

{{Monoamine neurotoxins