monoamine neurotoxin

{{Short description|Compounds that damage or destroy monoaminergic neurons}}

File:6-Hydroxydopamine.svg (6-hydroxydopamine), a selective dopaminergic and noradrenergic neurotoxin.]]

A monoamine neurotoxin, or monoaminergic neurotoxin, is a drug that selectively damages or destroys monoaminergic neurons.{{cite book | vauthors = Kostrzewa RM | title=Handbook of Neurotoxicity | chapter=Survey of Selective Monoaminergic Neurotoxins Targeting Dopaminergic, Noradrenergic, and Serotoninergic Neurons | publisher=Springer International Publishing | publication-place=Cham | date=2022 | isbn=978-3-031-15079-1 | doi=10.1007/978-3-031-15080-7_53 | pages=159–198}} Monoaminergic neurons are neurons that signal via stimulation by monoamine neurotransmitters including serotonin, dopamine, and norepinephrine.

Examples of monoamine neurotoxins include the serotonergic neurotoxins para-chloroamphetamine (PCA), methylenedioxymethamphetamine (MDMA), and 5,7-dihydroxytryptamine (5,7-DHT); the dopaminergic neurotoxins oxidopamine (6-hydroxydopamine), MPTP, and methamphetamine; 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, hyperthermia, oxidative stress and antioxidant depletion, and/or drug metabolites may all be involved in the neurotoxicity.{{cite book | author1-last=Baggott | author1-first=Matthew | author2-last= Mendelson | author2-first=John | chapter=Does MDMA Cause Brain Damage? | pages=110–145, 396–404 | editor1-last=Holland | editor1-first=J. | title=Ecstasy: The Complete Guide: A Comprehensive Look at the Risks and Benefits of MDMA | publisher=Inner Traditions/Bear | year=2001 | isbn=978-0-89281-857-0 | chapter-url=https://www.erowid.org/chemicals/mdma/mdma_neurotoxicity1.shtml | url=https://books.google.com/books?id=CUCcyklcO00C | access-date=24 November 2024 | quote = While a single injection of MDMA into the brain (intracerebroventricularly) had no effect on TPH activity, slow infusion of 1 mg/kg MDMA into the brain over 1 hr produced enough oxidative stress to acutely reduce TPH activity (Schmidt and Taylor 1988). The acute decrease in TPH activity is an early effect of MDMA and can be measured at post 15 min (Stone et al. 1989b). TPH inactivation can also be produced by non-neurotoxic MDMA doses (Schmidt and Taylor 1988; Stone et al. 1989a; Stone et al. 1989b). It therefore appears that MDMA rapidly induces oxidative stress but only produces neurotoxicity when endogenous free radical scavenging systems are overwhelmed.}}{{cite journal | vauthors = Sprague JE, Everman SL, Nichols DE | title = An integrated hypothesis for the serotonergic axonal loss induced by 3,4-methylenedioxymethamphetamine | journal = Neurotoxicology | volume = 19 | issue = 3 | pages = 427–441 | date = June 1998 | pmid = 9621349 | doi = | url = https://www.researchgate.net/publication/13663847}} 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.{{cite journal | vauthors = Rothman RB, Jayanthi S, Cadet JL, Wang X, Dersch CM, Baumann MH | title = Substituted amphetamines that produce long-term serotonin depletion in rat brain ("neurotoxicity") do not decrease serotonin transporter protein expression | journal = Ann N Y Acad Sci | volume = 1025 | issue = 1| pages = 151–161 | date = October 2004 | pmid = 15542713 | doi = 10.1196/annals.1316.020 | bibcode = 2004NYASA1025..151R | url = }}{{cite journal | vauthors = Fantegrossi WE, Woolverton WL, Kilbourn M, Sherman P, Yuan J, Hatzidimitriou G, Ricaurte GA, Woods JH, Winger G | title = Behavioral and neurochemical consequences of long-term intravenous self-administration of MDMA and its enantiomers by rhesus monkeys | journal = Neuropsychopharmacology | volume = 29 | issue = 7 | pages = 1270–1281 | date = July 2004 | pmid = 15039771 | doi = 10.1038/sj.npp.1300442 | url = }}

Dopaminergic neurotoxins can induce a Parkinson's disease-like condition in animals and humans.{{cite journal | vauthors = Grünblatt E, Mandel S, Youdim MB | title = MPTP and 6-hydroxydopamine-induced neurodegeneration as models for Parkinson's disease: neuroprotective strategies | journal = J Neurol | volume = 247 | issue = Suppl 2 | pages = II95–102 | date = April 2000 | pmid = 10991672 | doi = 10.1007/pl00022909 | url = }} Serotonergic neurotoxins have been associated with cognitive and memory deficits and psychiatric changes.{{cite journal | vauthors = Parrott AC | title = Recreational Ecstasy/MDMA, the serotonin syndrome, and serotonergic neurotoxicity | journal = Pharmacol Biochem Behav | volume = 71 | issue = 4 | pages = 837–844 | date = April 2002 | pmid = 11888574 | doi = 10.1016/s0091-3057(01)00711-0 | url = }}{{cite journal | vauthors = Parrott AC | title = MDMA, serotonergic neurotoxicity, and the diverse functional deficits of recreational 'Ecstasy' users | journal = Neurosci Biobehav Rev | volume = 37 | issue = 8 | pages = 1466–1484 | date = September 2013 | pmid = 23660456 | doi = 10.1016/j.neubiorev.2013.04.016 | url = }}{{cite journal | vauthors = Montgomery C, Roberts CA | title = Neurological and cognitive alterations induced by MDMA in humans | journal = Exp Neurol | volume = 347 | issue = | article-number = 113888 | date = January 2022 | pmid = 34624331 | doi = 10.1016/j.expneurol.2021.113888 | url = https://researchonline.ljmu.ac.uk/id/eprint/15629/3/Montgomery_Roberts_2021%20Review.pdf}}

List of monoamine neurotoxins

=Serotonergic neurotoxins=

==Phenethylamines==

2,4-Dichloroamphetamine (2,4-DCA)
2,4,5-Trihydroxyamphetamine (2,4,5-THA)
2,4,5-Trihydroxymethamphetamine (2,4,5-THMA)
3-Chloroamphetamine (3-CA){{cite journal | vauthors = Fuller RW, Baker JC | title = Long-lasting reduction of brain 5-hydroxytryptamine concentration by 3-chloramphetamine and 4-chloroamphetamine in iprindole-treated rats | journal = J Pharm Pharmacol | volume = 26 | issue = 11 | pages = 912–914 | date = November 1974 | pmid = 4156568 | doi = 10.1111/j.2042-7158.1974.tb09206.x | url = }}
3,4-Dichloroamphetamine (3,4-DCA){{cite book | vauthors = Biel JH, Bopp BA | title=Stimulants | chapter=Amphetamines: Structure-Activity Relationships | publisher=Springer US | publication-place=Boston, MA | date=1978 | isbn=978-1-4757-0512-6 | doi=10.1007/978-1-4757-0510-2_1 | pages=1–39}}
3,4-Dihydroxyamphetamine (HHA; 3,4-DHA; α-methyldopamine; α-Me-DA)
3,4-Dihydroxymethamphetamine (HHMA; 3,4-DHMA; α-methylepinine; α,N-dimethyldopamine)
3,4-Methylenedioxyamphetamine (MDA)
3,4-Methylenedioxyethylamphetamine (MDEA){{cite journal | vauthors = Oeri HE | title = Beyond ecstasy: Alternative entactogens to 3,4-methylenedioxymethamphetamine with potential applications in psychotherapy | journal = J Psychopharmacol | volume = 35 | issue = 5 | pages = 512–536 | date = May 2021 | pmid = 32909493 | pmc = 8155739 | doi = 10.1177/0269881120920420 | url = }}
3,4-Methylenedioxymethamphetamine (MDMA)
4-Chlorophenylisobutylamine (4-CAB; 4-chloro-α-desmethyl-α-ethylamphetamine; α-ethyl-PCA)
5-MAPB{{cite conference | vauthors = Johnson CB, Burroughs RL, Baggott MJ, Davidson CJ, Perrine SA, Baker LE | title = 314.03 / RR6 - Locomotor stimulant effects and persistent serotonin depletions following [1-Benzofuran-5-yl)-N-methylpropan-2-amine (5-MAPB) treatment in Sprague-Dawley rats | conference = Society for Neuroscience Conference, Nov. 14, 2022, San Diego, CA | date = 2022 | url = https://www.abstractsonline.com/pp8/#!/10619/presentation/67382 | quote = 5-MAPB has been marketed as a less neurotoxic analogue of MDMA, but no studies have addressed whether 5-MAPB can cause the long lasting serotonergic changes seen with high or repeated MDMA dosing. [...] Neurochemical analyses indicated a statistically significant reduction in 5‑HT and 5-HIAA in all brain regions assessed 24 hours and two weeks after 6 mg/kg 5‑MAPB, with no statistically significant differences in monoamine levels between 1.2 mg/kg and saline-treated rats. There were also non-significant trends for reductions in striatal dopamine at both time intervals after 6 mg/kg 5-MAPB. These results show that 5-MAPB can dose-dependently produce persistent changes in 5-HT and 5-HIAA that appear analogous to those produced by MDMA.}}
Fenfluramine{{cite journal | vauthors = McCann UD, Seiden LS, Rubin LJ, Ricaurte GA | title = Brain serotonin neurotoxicity and primary pulmonary hypertension from fenfluramine and dexfenfluramine. A systematic review of the evidence | journal = JAMA | volume = 278 | issue = 8 | pages = 666–672 | date = August 1997 | pmid = 9272900 | doi = 10.1001/jama.1997.03550080076043 | url = }}{{cite journal | vauthors = Rothman RB, Baumann MH | title = Serotonin releasing agents. Neurochemical, therapeutic and adverse effects | journal = Pharmacol Biochem Behav | volume = 71 | issue = 4 | pages = 825–836 | date = April 2002 | pmid = 11888573 | doi = 10.1016/s0091-3057(01)00669-4 | url = }}{{cite journal | vauthors = Johnson MP, Nichols DE | title = Comparative serotonin neurotoxicity of the stereoisomers of fenfluramine and norfenfluramine | journal = Pharmacol Biochem Behav | volume = 36 | issue = 1 | pages = 105–109 | date = May 1990 | pmid = 2140899 | doi = 10.1016/0091-3057(90)90133-3 | url = }}
Mephedrone
Methamphetamine
Methylbenzodioxolylbutanamine (MBDB)
Methylone{{cite journal | vauthors = Daziani G, Lo Faro AF, Montana V, Goteri G, Pesaresi M, Bambagiotti G, Montanari E, Giorgetti R, Montana A | title = Synthetic Cathinones and Neurotoxicity Risks: A Systematic Review | journal = Int J Mol Sci | volume = 24 | issue = 7 | date = March 2023 | page = 6230 | pmid = 37047201 | pmc = 10093970 | doi = 10.3390/ijms24076230 | doi-access = free | url = }}
Norfenfluramine{{cite journal | vauthors = Caccia S, Anelli M, Ferrarese A, Fracasso C, Garattini S | title = The role of d-norfenfluramine in the indole-depleting effect of d-fenfluramine in the rat | journal = Eur J Pharmacol | volume = 233 | issue = 1 | pages = 71–77 | date = March 1993 | pmid = 7682511 | doi = 10.1016/0014-2999(93)90350-q | url = }}
para-Bromoamphetamine (PBA; 4-bromoamphetamine; 4-BA){{cite journal | vauthors = Harvey JA | title = Neurotoxic action of halogenated amphetamines | journal = Ann N Y Acad Sci | volume = 305 | issue = 1| pages = 289–304 | date = June 1978 | pmid = 81648 | doi = 10.1111/j.1749-6632.1978.tb31530.x | bibcode = 1978NYASA.305..289H | url = }}
para-Bromomethamphetamine (PBMA; 4-bromomethamphetamine; 4-BMA){{cite journal | vauthors = Fuller RW | title = Structure-activity relationships among the halogenated amphetamines | journal = Ann N Y Acad Sci | volume = 305 | issue = 1| pages = 147–159 | date = June 1978 | pmid = 152079 | doi = 10.1111/j.1749-6632.1978.tb31518.x | bibcode = 1978NYASA.305..147F | url = }}{{cite journal | vauthors = Georgiev VP, Petkova BP | title = The effect of p-bromomethamphetamine (V-111), a selective serotoninergic amphetamine, on the convulsive seizure excitability threshold in mice | journal = Neuropharmacology | volume = 15 | issue = 12 | pages = 763–766 | date = December 1976 | pmid = 138097 | doi = 10.1016/0028-3908(76)90005-8 | url = }}
para-Chloroamphetamine (PCA; 4-chloroamphetamine; 4-CA)
para-Chloromethamphetamine (PCMA; 4-chloromethamphetamine; 4-PCMA){{cite book | last=Shulgin | first=Alexander T. | title=Stimulants | chapter=Psychotomimetic Drugs: Structure-Activity Relationships | publisher=Springer US | publication-place=Boston, MA | year=1978 | isbn=978-1-4757-0512-6 | doi=10.1007/978-1-4757-0510-2_6 | pages=243–333}}
para-Iodoamphetamine (PIA; 4-iodoamphetamine; 4-IA){{cite journal | vauthors = Nichols DE, Marona-Lewicka D, Huang X, Johnson MP | title = Novel serotonergic agents | journal = Drug des Discov | volume = 9 | issue = 3–4 | pages = 299–312 | date = 1993 | pmid = 8400010 | doi = | url = https://bitnest.netfirms.com/external/DrugDes.Disc/9.299 }}{{cite journal | vauthors = Iversen L, White M, Treble R | title = Designer psychostimulants: pharmacology and differences | journal = Neuropharmacology | volume = 87 | issue = | pages = 59–65 | date = December 2014 | pmid = 24456744 | doi = 10.1016/j.neuropharm.2014.01.015 | url = }}

==Tryptamines==

4-Hydroxy-5-methoxytryptamine (4-HO-5-MeO-T){{cite journal | vauthors = Horn AS, Baumgarten HG, Schlosserberger HG | title = Inhibition of the uptake of 5-hydroxytryptamine, noradrenaline and dopamine into rat brain homogenates by various hydroxylated tryptamines | journal = J Neurochem | volume = 21 | issue = 1 | pages = 233–236 | date = July 1973 | pmid = 4720899 | doi = 10.1111/j.1471-4159.1973.tb04242.x | url = }}{{cite journal | last=Schlossberger | first=H. G. | title=Synthesis and Chemical Properties of Some Indole Derivatives | journal=Annals of the New York Academy of Sciences | volume=305 | issue=1 | date=1978 | issn=0077-8923 | doi=10.1111/j.1749-6632.1978.tb31508.x | pages=25–35| bibcode=1978NYASA.305...25S }}
4,5-Dihydroxytryptamine (4,5-DHT){{cite journal | vauthors = Nobin A, Björklund A | title = Degenerative effects of various neurotoxic indoleamines on central monoamine neurons | journal = Ann N Y Acad Sci | volume = 305 | issue = 1| pages = 305–327 | date = June 1978 | pmid = 360938 | doi = 10.1111/j.1749-6632.1978.tb31531.x | bibcode = 1978NYASA.305..305N | url = }}{{cite journal | vauthors = Björklund A, Nobin A, Stenevi U | title = The use of neurotoxic dihydroxytryptamines as tools for morphological studies and localized lesioning of central indolamine neurons | journal = Z Zellforsch Mikrosk Anat | volume = 145 | issue = 4 | pages = 479–501 | date = December 1973 | pmid = 4774982 | doi = 10.1007/BF00306720 | url = }}
5,6-Dihydroxytryptamine (5,6-DHT){{cite book | last1=Paterak | first1=Justyna | last2=Stefański | first2=Roman | title=Handbook of Neurotoxicity | chapter=5,6- and 5,7-Dihydroxytryptamines as Serotoninergic Neurotoxins | publisher=Springer International Publishing | publication-place=Cham | date=2022 | isbn=978-3-031-15079-1 | doi=10.1007/978-3-031-15080-7_76 | pages=691–717}}{{cite journal | vauthors = Baumgarten HG, Lachenmayer L | title = Serotonin neurotoxins--past and present | journal = Neurotox Res | volume = 6 | issue = 7–8 | pages = 589–614 | date = 2004 | pmid = 15639791 | doi = 10.1007/BF03033455 | url = }}
5,7-Dihydroxytryptamine (5,7-DHT)
6,7-Dihydroxytryptamine (6,7-DHT){{cite journal | vauthors = Massotti M, Scotti de Carolis A, Longo VG | title = Effects of three dihydroxylated derivatives of tryptamine on the behavior and on brain amine content in mice | journal = Pharmacol Biochem Behav | volume = 2 | issue = 6 | pages = 769–776 | date = 1974 | pmid = 4549398 | doi = 10.1016/0091-3057(74)90109-9 | url = }}
α-Ethyltryptamine (αET){{cite journal | vauthors = Glennon RA, Dukat MG | title = α-Ethyltryptamine: A Ratiocinatory Review of a Forgotten Antidepressant | journal = ACS Pharmacol Transl Sci | volume = 6 | issue = 12 | pages = 1780–1789 | date = December 2023 | pmid = 38093842 | doi = 10.1021/acsptsci.3c00139 | pmc = 10714429 | url = }}{{cite journal | vauthors = Huang XM, Johnson MP, Nichols DE | title = Reduction in brain serotonin markers by alpha-ethyltryptamine (Monase) | journal = Eur J Pharmacol | volume = 200 | issue = 1 | pages = 187–190 | date = July 1991 | pmid = 1722753 | doi = 10.1016/0014-2999(91)90686-k | url = }}

==2-Aminoindans==

5-Iodo-2-aminoindan (5-IAI) (weak){{cite journal | vauthors = Sainsbury PD, Kicman AT, Archer RP, King LA, Braithwaite RA | title = Aminoindanes--the next wave of 'legal highs'? | journal = Drug Test Anal | volume = 3 | issue = 7–8 | pages = 479–482 | date = 2011 | pmid = 21748859 | doi = 10.1002/dta.318 | url = }}
5-Methoxy-6-methyl-2-aminoindane (MMAI) (weak; alone and with amphetamine){{cite book | last1=Brandt | first1=Simon D. | last2=Braithwaite | first2=Robin A. | last3=Evans-Brown | first3=Michael | last4=Kicman | first4=Andrew T. | title=Novel Psychoactive Substances | chapter=Aminoindane Analogues | publisher=Elsevier | date=2013 | isbn=978-0-12-415816-0 | doi=10.1016/b978-0-12-415816-0.00011-0 | pages=261–283}}{{cite journal | vauthors = Johnson MP, Nichols DE | title = Combined administration of a non-neurotoxic 3,4-methylenedioxymethamphetamine analogue with amphetamine produces serotonin neurotoxicity in rats | journal = Neuropharmacology | volume = 30 | issue = 7 | pages = 819–822 | date = July 1991 | pmid = 1717873 | doi = 10.1016/0028-3908(91)90192-e | url = }}{{cite journal | vauthors = Johnson MP, Conarty PF, Nichols DE | title = [3H]monoamine releasing and uptake inhibition properties of 3,4-methylenedioxymethamphetamine and p-chloroamphetamine analogues | journal = Eur J Pharmacol | volume = 200 | issue = 1 | pages = 9–16 | date = July 1991 | pmid = 1685125 | doi = 10.1016/0014-2999(91)90659-e | url = }}
5,6-Methylenedioxy-2-aminoindan (MDAI) (weak; alone and with amphetamine){{cite journal | vauthors = Corkery JM, Elliott S, Schifano F, Corazza O, Ghodse AH | title = MDAI (5,6-methylenedioxy-2-aminoindane; 6,7-dihydro-5H-cyclopenta[f][1,3]benzodioxol-6-amine; 'sparkle'; 'mindy') toxicity: a brief overview and update | journal = Hum Psychopharmacol | volume = 28 | issue = 4 | pages = 345–355 | date = July 2013 | pmid = 23881883 | doi = 10.1002/hup.2298 | url = }}{{cite journal | vauthors = Johnson MP, Huang XM, Nichols DE | title = Serotonin neurotoxicity in rats after combined treatment with a dopaminergic agent followed by a nonneurotoxic 3,4-methylenedioxymethamphetamine (MDMA) analogue | journal = Pharmacol Biochem Behav | volume = 40 | issue = 4 | pages = 915–922 | date = December 1991 | pmid = 1726189 | doi = 10.1016/0091-3057(91)90106-c | url = }}

=Dopaminergic neurotoxins=

==Phenethylamines==

2,4,5-Trihydroxyamphetamine (2,4,5-THA){{cite journal | vauthors = Gibb JW, Johnson M, Elayan I, Lim HK, Matsuda L, Hanson GR | title = Neurotoxicity of amphetamines and their metabolites | journal = NIDA Res Monogr | volume = 173 | issue = | pages = 128–145 | date = 1997 | pmid = 9260187 | doi = | url = https://web.archive.org/web/20170705055839id_/https://archives.drugabuse.gov/pdf/monographs/monograph173/128-145_Gibb.pdf}}
2,4,5-Trihydroxymethamphetamine (2,4,5-THMA)
3,4-Methylenedioxymethamphetamine (MDMA) (in mice but not in humans){{cite journal | vauthors = Aguilar MA, García-Pardo MP, Parrott AC | title = Of mice and men on MDMA: A translational comparison of the neuropsychobiological effects of 3,4-methylenedioxymethamphetamine ('Ecstasy') | journal = Brain Res | volume = 1727 | issue = | article-number = 146556 | date = January 2020 | pmid = 31734398 | doi = 10.1016/j.brainres.2019.146556 | url = }}
4-Methylmethamphetamine (4-MMA; mephedrine)
6-Hydroxydopa (6-OH-DOPA, 6-OHDOPA){{cite book | vauthors = Kostrzewa RM | title = Neurotoxin Modeling of Brain Disorders—Life-long Outcomes in Behavioral Teratology | chapter = Perinatal Lesioning and Lifelong Effects of the Noradrenergic Neurotoxin 6-Hydroxydopa | series = Current Topics in Behavioral Neurosciences | volume = 29 | pages = 43–50 | date = 2016 | pmid = 26660536 | doi = 10.1007/7854_2015_414 | isbn = 978-3-319-34134-7 | chapter-url = }}{{cite journal | vauthors = Kostrzewa RM, Brus R | title = Destruction of catecholamine-containing neurons by 6-hydroxydopa, an endogenous amine oxidase cofactor | journal = Amino Acids | volume = 14 | issue = 1–3 | pages = 175–179 | date = 1998 | pmid = 9871458 | doi = 10.1007/BF01345259 | url = }}
6-Hydroxydopamine quinone (6-OHDA quinone; oxidopamine quinone){{cite journal | vauthors = Villa M, Muñoz P, Ahumada-Castro U, Paris I, Jiménez A, Martínez I, Sevilla F, Segura-Aguilar J | title = One-electron reduction of 6-hydroxydopamine quinone is essential in 6-hydroxydopamine neurotoxicity | journal = Neurotox Res | volume = 24 | issue = 1 | pages = 94–101 | date = July 2013 | pmid = 23385626 | doi = 10.1007/s12640-013-9382-7 | url = | hdl = 10533/128562 | hdl-access = free }}
Amphetamine
Mephedrone
Methamphetamine{{cite journal | vauthors = Seiden LS, Sabol KE | title = Methamphetamine and methylenedioxymethamphetamine neurotoxicity: possible mechanisms of cell destruction | journal = NIDA Res Monogr | volume = 163 | issue = | pages = 251–276 | date = 1996 | pmid = 8809863 | doi = | url = https://corpora.tika.apache.org/base/docs/govdocs1/205/205594.pdf}}{{cite journal | vauthors = Itzhak Y, Achat-Mendes C | title = Methamphetamine and MDMA (ecstasy) neurotoxicity: 'of mice and men' | journal = IUBMB Life | volume = 56 | issue = 5 | pages = 249–255 | date = May 2004 | pmid = 15370888 | doi = 10.1080/15216540410001727699 | url = }}
Methcathinone{{cite journal | vauthors = Anneken JH, Angoa-Pérez M, Sati GC, Crich D, Kuhn DM | title = Dissecting the Influence of Two Structural Substituents on the Differential Neurotoxic Effects of Acute Methamphetamine and Mephedrone Treatment on Dopamine Nerve Endings with the Use of 4-Methylmethamphetamine and Methcathinone | journal = J Pharmacol Exp Ther | volume = 360 | issue = 3 | pages = 417–423 | date = March 2017 | pmid = 28039330 | pmc = 5325074 | doi = 10.1124/jpet.116.237768 | url = }}{{cite journal | vauthors = Anneken JH, Angoa-Perez M, Sati GC, Crich D, Kuhn DM | title = Assessing the role of dopamine in the differential neurotoxicity patterns of methamphetamine, mephedrone, methcathinone and 4-methylmethamphetamine | journal = Neuropharmacology | volume = 134 | issue = Pt A | pages = 46–56 | date = May 2018 | pmid = 28851615 | pmc = 6083857 | doi = 10.1016/j.neuropharm.2017.08.033 | url = }}
Methylone
Oxidopamine (6-hydroxydopamine; 6-OHDA){{cite book | vauthors = Glinka Y, Gassen M, Youdim MB | chapter = Mechanism of 6-hydroxydopamine neurotoxicity | title = Advances in Research on Neurodegeneration | journal = Journal of Neural Transmission. Supplementum | series = Journal of Neural Transmission. Supplementa | volume = 50 | issue = | pages = 55–66 | date = 1997 | pmid = 9120425 | doi = 10.1007/978-3-7091-6842-4_7 | isbn = 978-3-211-82898-4 | chapter-url = }}{{cite journal | vauthors = Hernandez-Baltazar D, Zavala-Flores LM, Villanueva-Olivo A | title = The 6-hydroxydopamine model and parkinsonian pathophysiology: Novel findings in an older model | journal = Neurologia | volume = 32 | issue = 8 | pages = 533–539 | date = October 2017 | pmid = 26304655 | doi = 10.1016/j.nrl.2015.06.011 | url =http://eprints.uanl.mx/14502/1/15.pdf }}{{cite journal | vauthors = Varešlija D, Tipton KF, Davey GP, McDonald AG | title = 6-Hydroxydopamine: a far from simple neurotoxin | journal = J Neural Transm (Vienna) | volume = 127 | issue = 2 | pages = 213–230 | date = February 2020 | pmid = 31894418 | doi = 10.1007/s00702-019-02133-6 | url = }}

===Dopamine and metabolites===

3,4-Dihydroxyphenylacetaldehyde (DOPAL; dopamine aldehyde){{cite journal | vauthors = Goldstein DS | title = The catecholaldehyde hypothesis: where MAO fits in | journal = J Neural Transm (Vienna) | volume = 127 | issue = 2 | pages = 169–177 | date = February 2020 | pmid = 31807952 | pmc = 10680281 | doi = 10.1007/s00702-019-02106-9 | url = }}{{cite journal | vauthors = Goldstein DS | title = The Catecholaldehyde Hypothesis for the Pathogenesis of Catecholaminergic Neurodegeneration: What We Know and What We Do Not Know | journal = Int J Mol Sci | volume = 22 | issue = 11 | date = June 2021 | page = 5999 | pmid = 34206133 | pmc = 8199574 | doi = 10.3390/ijms22115999 | doi-access = free | url = }}
5-S-Cysteinyldopamine (5-S-CyS-DA){{cite journal | vauthors = Badillo-Ramírez I, Saniger JM, Rivas-Arancibia S | title = 5-S-cysteinyl-dopamine, a neurotoxic endogenous metabolite of dopamine: Implications for Parkinson's disease | journal = Neurochem Int | volume = 129 | issue = | article-number = 104514 | date = October 2019 | pmid = 31369776 | doi = 10.1016/j.neuint.2019.104514 | url = }}
DOPA quinone
DOPAL quinone{{cite journal | vauthors = Goldstein DS, Sharabi Y | title = The heart of PD: Lewy body diseases as neurocardiologic disorders | journal = Brain Res | volume = 1702 | issue = | pages = 74–84 | date = January 2019 | pmid = 29030055 | pmc = 10712237 | doi = 10.1016/j.brainres.2017.09.033 | url = }}
Dopamine{{cite journal | vauthors = Chakrabarti S, Bisaglia M | title = Oxidative Stress and Neuroinflammation in Parkinson's Disease: The Role of Dopamine Oxidation Products | journal = Antioxidants | volume = 12 | issue = 4 | date = April 2023 | page = 955 | pmid = 37107329 | pmc = 10135711 | doi = 10.3390/antiox12040955 | doi-access = free | url = }}
Dopamine quinone{{cite journal | vauthors = Miyazaki I, Asanuma M | title = Approaches to prevent dopamine quinone-induced neurotoxicity | journal = Neurochem Res | volume = 34 | issue = 4 | pages = 698–706 | date = April 2009 | pmid = 18770028 | doi = 10.1007/s11064-008-9843-1 | url = }}{{cite journal | vauthors = Asanuma M, Miyazaki I, Ogawa N | title = Dopamine- or L-DOPA-induced neurotoxicity: the role of dopamine quinone formation and tyrosinase in a model of Parkinson's disease | journal = Neurotox Res | volume = 5 | issue = 3 | pages = 165–176 | date = 2003 | pmid = 12835121 | doi = 10.1007/BF03033137 | url = }}
N-Methylnorsalsolinol
Norsalsolinol{{cite journal | vauthors = Cao Y, Li B, Ismail N, Smith K, Li T, Dai R, Deng Y | title = Neurotoxicity and Underlying Mechanisms of Endogenous Neurotoxins | journal = Int J Mol Sci | volume = 22 | issue = 23 | date = November 2021 | page = 12805 | pmid = 34884606 | pmc = 8657695 | doi = 10.3390/ijms222312805 | doi-access = free | url = }}
Salsolinol{{cite journal | vauthors = Kurnik-Łucka M, Panula P, Bugajski A, Gil K | title = Salsolinol: an Unintelligible and Double-Faced Molecule-Lessons Learned from In Vivo and In Vitro Experiments | journal = Neurotox Res | volume = 33 | issue = 2 | pages = 485–514 | date = February 2018 | pmid = 29063289 | pmc = 5766726 | doi = 10.1007/s12640-017-9818-6 | url = }}

==Tryptamines==

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

==MPTP-related==

2′-CH₃-MPTP (2′-methyl-MPTP){{cite journal | vauthors = Maret G, Testa B, Jenner P, el Tayar N, Carrupt PA | title = The MPTP story: MAO activates tetrahydropyridine derivatives to toxins causing parkinsonism | journal = Drug Metab Rev | volume = 22 | issue = 4 | pages = 291–332 | date = 1990 | pmid = 2253555 | doi = 10.3109/03602539009041087 | url = }}{{cite journal | vauthors = Manaye KF, Sonsalla PK, Barnett G, Heikkila RE, Woodward DJ, Smith WK, German DC | title = 1-Methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine (2'CH3-MPTP)-induced degeneration of mesostriatal dopaminergic neurons in the mouse: biochemical and neuroanatomical studies | journal = Brain Res | volume = 491 | issue = 2 | pages = 307–315 | date = July 1989 | pmid = 2765888 | doi = 10.1016/0006-8993(89)90065-6 | url = }}{{cite journal | vauthors = Heikkila RE, Sieber BA, Manzino L, Sonsalla PK | title = Some features of the nigrostriatal dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the mouse | journal = Mol Chem Neuropathol | volume = 10 | issue = 3 | pages = 171–183 | date = June 1989 | pmid = 2669769 | doi = 10.1007/BF03159727 | url = }}{{cite journal | vauthors = Youngster SK, Duvoisin RC, Hess A, Sonsalla PK, Kindt MV, Heikkila RE | title = 1-Methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine (2'-CH3-MPTP) is a more potent dopaminergic neurotoxin than MPTP in mice | journal = Eur J Pharmacol | volume = 122 | issue = 2 | pages = 283–287 | date = March 1986 | pmid = 3486770 | doi = 10.1016/0014-2999(86)90115-9 | url = }}{{cite journal | vauthors = Rose S, Nomoto M, Jackson EA, Gibb WR, Jenner P, Marsden CD | title = 1-Methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine (2'-methyl-MPTP) is less neurotoxic than MPTP in the common marmoset | journal = Eur J Pharmacol | volume = 181 | issue = 1–2 | pages = 97–103 | date = May 1990 | pmid = 2117541 | doi = 10.1016/0014-2999(90)90249-6 | url = }}
Haloperidol{{cite journal | vauthors = Igarashi K | title=The Possible Role of an Active Metafbollte Derived from the Neuroleptic Agent Haloperidol in Drug-Induced Parkinsonism | journal=Journal of Toxicology: Toxin Reviews | volume=17 | issue=1 | date=1998 | issn=0731-3837 | doi=10.3109/15569549809006488 | pages=27–38}}
HPP⁺ (haloperidol pyridinium)
HPTP
MPP⁺ (cyperquat){{cite journal | vauthors = Przedborski S, Vila M | title=MPTP: a review of its mechanisms of neurotoxicity | journal=Clinical Neuroscience Research | volume=1 | issue=6 | date=2001 | doi=10.1016/S1566-2772(01)00019-6 | pages=407–418}}{{cite journal | vauthors = Dinis-Oliveira RJ, Remião F, Carmo H, Duarte JA, Navarro AS, Bastos ML, Carvalho F | title = Paraquat exposure as an etiological factor of Parkinson's disease | journal = Neurotoxicology | volume = 27 | issue = 6 | pages = 1110–1122 | date = December 2006 | pmid = 16815551 | doi = 10.1016/j.neuro.2006.05.012 | bibcode = 2006NeuTx..27.1110D | url = | quote = Ironically, in the 1960s, MPP+ itself had been tested as an herbicide under the commercial name of cyperquat (Di Monte, 2001).}}
MPTP

==Pesticides==

Benomyl
Daidzin
Dieldrin
Fenpropathrin{{cite journal | vauthors = Arsuffi-Marcon R, Souza LG, Santos-Miranda A, Joviano-Santos JV | title = Neurotoxicity of Pyrethroids in neurodegenerative diseases: From animals' models to humans' studies | journal = Chem Biol Interact | volume = 391 | issue = | article-number = 110911 | date = March 2024 | pmid = 38367681 | doi = 10.1016/j.cbi.2024.110911 | bibcode = 2024CBI...39110911A | url = }}{{cite journal | vauthors = Xiong J, Zhang X, Huang J, Chen C, Chen Z, Liu L, Zhang G, Yang J, Zhang Z, Zhang Z, Lin Z, Xiong N, Wang T | title = Fenpropathrin, a Widely Used Pesticide, Causes Dopaminergic Degeneration | journal = Mol Neurobiol | volume = 53 | issue = 2 | pages = 995–1008 | date = March 2016 | pmid = 25575680 | pmc = 5333774 | doi = 10.1007/s12035-014-9057-2 | url = }}{{cite journal | vauthors = Jiao Z, Wu Y, Qu S | title = Fenpropathrin induces degeneration of dopaminergic neurons via disruption of the mitochondrial quality control system | journal = Cell Death Discov | volume = 6 | issue = | article-number = 78 | date = 2020 | pmid = 32884840 | pmc = 7447795 | doi = 10.1038/s41420-020-00313-y | url = }}
Mancozeb
Maneb
Paraquat{{cite journal | vauthors = Kuter K, Smiałowska M, Wierońska J, Zieba B, Wardas J, Pietraszek M, Nowak P, Biedka I, Roczniak W, Konieczny J, Wolfarth S, Ossowska K | title = Toxic influence of subchronic paraquat administration on dopaminergic neurons in rats | journal = Brain Res | volume = 1155 | issue = | pages = 196–207 | date = June 2007 | pmid = 17493592 | doi = 10.1016/j.brainres.2007.04.018 | url = }}
Rotenone{{cite journal | vauthors = Bastías-Candia S, Zolezzi JM, Inestrosa NC | title = Revisiting the Paraquat-Induced Sporadic Parkinson's Disease-Like Model | journal = Mol Neurobiol | volume = 56 | issue = 2 | pages = 1044–1055 | date = February 2019 | pmid = 29862459 | doi = 10.1007/s12035-018-1148-z | url = }}{{cite journal | vauthors = Goldstein DS, Sullivan P, Cooney A, Jinsmaa Y, Kopin IJ, Sharabi Y | title = Rotenone decreases intracellular aldehyde dehydrogenase activity: implications for the pathogenesis of Parkinson's disease | journal = J Neurochem | volume = 133 | issue = 1 | pages = 14–25 | date = April 2015 | pmid = 25645689 | pmc = 4361358 | doi = 10.1111/jnc.13042 | url = }}
Ziram

==Others==

Aldehyde dehydrogenase (ALDH) inhibitors (e.g., disulfiram, methylmercury){{cite journal | vauthors = Masato A, Plotegher N, Boassa D, Bubacco L | title = Impaired dopamine metabolism in Parkinson's disease pathogenesis | journal = Mol Neurodegener | volume = 14 | issue = 1 | article-number = 35 | date = August 2019 | pmid = 31488222 | pmc = 6728988 | doi = 10.1186/s13024-019-0332-6 | doi-access = free | url = }}{{cite journal | vauthors = Doorn JA, Florang VR, Schamp JH, Vanle BC | title = Aldehyde dehydrogenase inhibition generates a reactive dopamine metabolite autotoxic to dopamine neurons | journal = Parkinsonism Relat Disord | volume = 20 Suppl 1 | issue = 1 | pages = S73–S75 | date = January 2014 | pmid = 24262193 | pmc = 3932615 | doi = 10.1016/S1353-8020(13)70019-1 | url = }}{{cite journal | vauthors = Legros H, Dingeval MG, Janin F, Costentin J, Bonnet JJ | title = Toxicity of a treatment associating dopamine and disulfiram for catecholaminergic neuroblastoma SH-SY5Y cells: relationships with 3,4-dihydroxyphenylacetaldehyde formation | journal = Neurotoxicology | volume = 25 | issue = 3 | pages = 365–375 | date = March 2004 | pmid = 15019299 | doi = 10.1016/S0161-813X(03)00148-7 | bibcode = 2004NeuTx..25..365L | url = }}{{cite journal | vauthors = Tiernan CT, Edwin EA, Hawong HY, Ríos-Cabanillas M, Goudreau JL, Atchison WD, Lookingland KJ | title = Methylmercury impairs canonical dopamine metabolism in rat undifferentiated pheochromocytoma (PC12) cells by indirect inhibition of aldehyde dehydrogenase | journal = Toxicol Sci | volume = 144 | issue = 2 | pages = 347–356 | date = April 2015 | pmid = 25601988 | pmc = 4372664 | doi = 10.1093/toxsci/kfv001 | url = }}

=Noradrenergic neurotoxins=

=Unsorted or unknown=

5-Hydroxyindoleacetaldehyde (5-HIAL){{cite journal | vauthors = Cagle BS, Crawford RA, Doorn JA | title = Biogenic Aldehyde-Mediated Mechanisms of Toxicity in Neurodegenerative Disease | journal = Curr Opin Toxicol | volume = 13 | issue = | pages = 16–21 | date = February 2019 | pmid = 31304429 | pmc = 6625780 | doi = 10.1016/j.cotox.2018.12.002 | bibcode = 2019COTox..13...16C | url = }}{{cite journal | vauthors = Matveychuk D, MacKenzie EM, Kumpula D, Song MS, Holt A, Kar S, Todd KG, Wood PL, Baker GB | title = Overview of the Neuroprotective Effects of the MAO-Inhibiting Antidepressant Phenelzine | journal = Cell Mol Neurobiol | volume = 42 | issue = 1 | pages = 225–242 | date = January 2022 | pmid = 33839994 | pmc = 8732914 | doi = 10.1007/s10571-021-01078-3 | url = }}{{cite journal | vauthors = Behl T, Kaur D, Sehgal A, Singh S, Sharma N, Zengin G, Andronie-Cioara FL, Toma MM, Bungau S, Bumbu AG | title = Role of Monoamine Oxidase Activity in Alzheimer's Disease: An Insight into the Therapeutic Potential of Inhibitors | journal = Molecules | volume = 26 | issue = 12 | date = June 2021 | page = 3724 | pmid = 34207264 | pmc = 8234097 | doi = 10.3390/molecules26123724 | doi-access = free | url = }}
RHPP⁺{{cite journal | vauthors = Górska A, Marszałł M, Sloderbach A | title = Neurotoksyczność pirydyniowych metabolitów haloperydolu | trans-title = The neurotoxicity of pyridinium metabolites of haloperidol | language = Polish | journal = Postepy Hig Med Dosw (Online) | volume = 69 | issue = | pages = 1169–1175 | date = October 2015 | pmid = 26561842 | doi = 10.5604/17322693.1175009 | doi-broken-date = 12 July 2025 | url = | doi-access = free }}{{cite journal | vauthors = Castagnoli N, Castagnoli KP, Van der Schyf CJ, Usuki E, Igarashi K, Steyn SJ, Riker RR | title = Enzyme-catalyzed bioactivation of cyclic tertiary amines to form potential neurotoxins | journal = Pol J Pharmacol | volume = 51 | issue = 1 | pages = 31–38 | date = 1999 | pmid = 10389142 | doi = | url = }}
RHPTP{{cite journal | vauthors = Avent KM, Usuki E, Eyles DW, Keeve R, Van der Schyf CJ, Castagnoli N, Pond SM | title = Haloperidol and its tetrahydropyridine derivative (HPTP) are metabolized to potentially neurotoxic pyridinium species in the baboon | journal = Life Sci | volume = 59 | issue = 17 | pages = 1473–1482 | date = 1996 | pmid = 8890926 | doi = 10.1016/0024-3205(96)00475-4 | url = }}{{cite journal | vauthors = Avent KM, Riker RR, Fraser GL, Van der Schyf CJ, Usuki E, Pond SM | title = Metabolism of haloperidol to pyridinium species in patients receiving high doses intravenously: is HPTP an intermediate? | journal = Life Sci | volume = 61 | issue = 24 | pages = 2383–2390 | date = 1997 | pmid = 9399630 | doi = 10.1016/s0024-3205(97)00955-7 | url = }}{{cite journal | last1=Ooms | first1=Frédéric | last2=Delvosal | first2=Sébastien | last3=Wouters | first3=Johan | last4=Durant | first4=François | last5=Dockendolf | first5=Gisella | last6=Van't Land | first6=Clinton | last7=Glass | first7=Thomas | last8=Castagnoli, Jr | first8=Neal | last9=Van der Schyf | first9=Cornelis J. | title=Empirical and molecular modeling study of the pyridinium species RHPP+, an abundant and potentially neurotoxic metabolite of haloperidol | journal=Journal of the Chemical Society, Perkin Transactions 2 | issue=9 | date=2000 | doi=10.1039/b002357o | pages=1781–1787}}{{cite journal | vauthors = Avent KM, DeVoss JJ, Gillam EM | title = Cytochrome P450-mediated metabolism of haloperidol and reduced haloperidol to pyridinium metabolites | journal = Chem Res Toxicol | volume = 19 | issue = 7 | pages = 914–920 | date = July 2006 | pmid = 16841959 | doi = 10.1021/tx0600090 | url = }}

monoamine neurotoxin

List of monoamine neurotoxins

=Serotonergic neurotoxins=

==Phenethylamines==

==Tryptamines==

==2-Aminoindans==

=Dopaminergic neurotoxins=

==Phenethylamines==

===Dopamine and metabolites===

==Tryptamines==

==Pesticides==

==Others==

=Noradrenergic neurotoxins=

=Unsorted or unknown=

See also

References

monoamine neurotoxin

List of monoamine neurotoxins

=Serotonergic neurotoxins=

==Phenethylamines==

==Tryptamines==

==2-Aminoindans==

==MPTP-related==

=Dopaminergic neurotoxins=

==Phenethylamines==

===Dopamine and metabolites===

==Tryptamines==

==MPTP-related==

==Pesticides==

==Others==

=Noradrenergic neurotoxins=

==Phenethylamines and related==

==Tryptamines and related==

==MPTP-related==

=Unsorted or unknown=

See also

References