Monoamine neurotoxin

Compounds that damage or destroy monoaminergic neurons

Oxidopamine (6-hydroxydopamine), a selective dopaminergic and noradrenergic neurotoxin.

A monoamine neurotoxin, or monoaminergic neurotoxin, is a drug that selectively damages or destroys monoaminergic neurons.[1] Monoaminergic neurons are neurons that signal via stimulation by monoamine neurotransmitters including serotonin, dopamine, and norepinephrine.[1]

Examples of monoamine neurotoxins include the serotonergic neurotoxins para-chloroamphetamine (PCA), methylenedioxymethamphetamine (MDMA), and 5,7-dihydroxytryptamine (5,7-DHT);[2] the dopaminergic neurotoxins oxidopamine (6-hydroxydopamine), MPTP, and methamphetamine; and the noradrenergic neurotoxins oxidopamine and DSP-4.[1]

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.[3][4] On the other hand, there is evidence that drug metabolites may not be involved.[3][4] Some research suggests that serotonergic neurotoxicity might represent neuroadaptive mechanisms rather than neuronal damage per se.[5][6]

Dopaminergic neurotoxins can induce a Parkinson's disease-like condition in animals and humans.[1][7] Serotonergic neurotoxins have been associated with cognitive and memory deficits and psychiatric changes.[8][9][10][11]

## List of monoamine neurotoxins

[edit]

### Serotonergic neurotoxins

[edit]

#### Phenethylamines

[edit]

* 2,4-Dichloroamphetamine (2,4-DCA)[12]
* 2,4,5-Trihydroxyamphetamine (2,4,5-THA)[13]
* 2,4,5-Trihydroxymethamphetamine (2,4,5-THMA)[13]
* 3-Chloroamphetamine (3-CA)[12][14]
* 3,4-Dichloroamphetamine (3,4-DCA)[12]
* 3,4-Dihydroxyamphetamine (HHA; 3,4-DHA; α-methyldopamine; α-Me-DA)[2]
* 3,4-Dihydroxymethamphetamine (HHMA; 3,4-DHMA; α-methylepinine; α,N-dimethyldopamine)[2]
* 3,4-Methylenedioxyamphetamine (MDA)[1][15][2][13]
* 3,4-Methylenedioxyethylamphetamine (MDEA)[15][16]
* 3,4-Methylenedioxymethamphetamine (MDMA)[1][2][17][18]
* 4-Chlorophenylisobutylamine (4-CAB; 4-chloro-α-desmethyl-α-ethylamphetamine; α-ethyl-PCA)[15]
* 5-MAPB[19]
* Fenfluramine[1][20][21][22]
* Mephedrone[23]
* Methamphetamine[1][18][13]
* Methylbenzodioxolylbutanamine (MBDB)[15][16]
* Methylone[23]
* Norfenfluramine[22][24]
* para-Bromoamphetamine (PBA; 4-bromoamphetamine; 4-BA)[25]
* para-Bromomethamphetamine (PBMA; 4-bromomethamphetamine; 4-BMA)[26][27]
* para-Chloroamphetamine (PCA; 4-chloroamphetamine; 4-CA)[1][2][16]
* para-Chloromethamphetamine (PCMA; 4-chloromethamphetamine; 4-PCMA)[12][28]
* para-Iodoamphetamine (PIA; 4-iodoamphetamine; 4-IA)[15][29]

#### Tryptamines

[edit]

* 4-Hydroxy-5-methoxytryptamine (4-HO-5-MeO-T)[30][31]
* 4,5-Dihydroxytryptamine (4,5-DHT)[32][33][31]
* 5,6-Dihydroxytryptamine (5,6-DHT)[34][1][2]
* 5,7-Dihydroxytryptamine (5,7-DHT)[34][1][2]
* 6,7-Dihydroxytryptamine (6,7-DHT)[32][35]
* α-Ethyltryptamine (αET)[16][36][37]

#### 2-Aminoindans

[edit]

* 5-Iodo-2-aminoindan (5-IAI) (weak)[38][16][15]
* 5-Methoxy-6-methyl-2-aminoindane (MMAI) (weak; alone and with amphetamine)[39][40][41]
* 5,6-Methylenedioxy-2-aminoindan (MDAI) (weak; alone and with amphetamine)[42][15][43]

#### MPTP-related

[edit]

* 2′-NH2-MPTP (2′-amino-MPTP)[1]
* Haloperidol[1][44]
* HPP+ (haloperidol pyridinium)[1][44]
* HPTP[1][45]

### Dopaminergic neurotoxins

[edit]

#### Phenethylamines

[edit]

* 2,4,5-Trihydroxyamphetamine (2,4,5-THA)[13]
* 2,4,5-Trihydroxymethamphetamine (2,4,5-THMA)[13]
* 3,4-Methylenedioxymethamphetamine (MDMA) (in mice but not in humans)[18][10]
* 4-Methylmethamphetamine (4-MMA; mephedrine)[46][47]
* 6-Hydroxydopa (6-OH-DOPA, 6-OHDOPA)[1][48][49]
* 6-Hydroxydopamine quinone (6-OHDA quinone; oxidopamine quinone)[50][51]
* Amphetamine[1]
* Mephedrone[23]
* Methamphetamine[1][17][18]
* Methcathinone[46][47]
* Methylone[23]
* Oxidopamine (6-hydroxydopamine; 6-OHDA)[52][53][50]

##### Dopamine and metabolites

[edit]

* 3,4-Dihydroxyphenylacetaldehyde (DOPAL; dopamine aldehyde)[54][55]
* 5-S-Cysteinyldopamine (5-S-CyS-DA)[56]
* DOPA quinone[57][58]
* DOPAL quinone[59]
* Dopamine[60]
* Dopamine quinone[57][58]
* N-Methylnorsalsolinol[61]
* Norsalsolinol[61]
* Salsolinol[61][62]

#### Tryptamines

[edit]

* 5,6-Dihydroxytryptamine (5,6-DHT)[34][63]
* 6,7-Dihydroxytryptamine (6,7-DHT)[32][35]

#### MPTP-related

[edit]

* 2′-CH3-MPTP (2′-methyl-MPTP)[64][65][66][67][68]
* Haloperidol[1][44]
* HPP+ (haloperidol pyridinium)[1][44]
* HPTP[1][45]
* MPP+ (cyperquat)[69][70]
* MPTP[69]

#### Pesticides

[edit]

* Benomyl[71]
* Daidzin[71]
* Dieldrin[71]
* Fenpropathrin[72][73][74]
* Mancozeb[75]
* Maneb[75]
* Paraquat[72][75][76]
* Rotenone[1][72][75][77]
* Ziram[71]

#### Others

[edit]

* Aldehyde dehydrogenase (ALDH) inhibitors (e.g., disulfiram, methylmercury)[71][78][79][80]

### Noradrenergic neurotoxins

[edit]

#### Phenethylamines and related

[edit]

* 2,4,5-Trihydroxyamphetamine (2,4,5-THA)[13]
* 3,4-Methylenedioxyamphetamine (MDA)[13]
* 3,4-Dihydroxyphenylglycolaldehyde (DOPEGAL; norepinephrine/epinephrine aldehyde)[81]
* 6-Hydroxydopa (6-OH-DOPA, 6-OHDOPA)[1][48][49]
* DSP-4[82][83]
* Oxidopamine (6-hydroxydopamine; 6-OHDA)[52][50]
* Xylamine[1]

#### Tryptamines and related

[edit]

* 4,5-Dihydroxytryptamine (4,5-DHT)[32][33]
* 5,6-Dihydroxytryptamine (5,6-DHT)[34][63]
* 5,7-Dihydroxytryptamine (5,7-DHT)[34][63]

#### MPTP-related

[edit]

* 2′-NH2-MPTP (2′-amino-MPTP)[1]

### Unsorted or unknown

[edit]

* 5-Hydroxyindoleacetaldehyde (5-HIAL)[84][85][86]
* RHPP+[87][45]
* RHPTP[88][89][90][91]

## See also

[edit]

* Monoamine-depleting agent

## References

[edit]

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* v
* t
* e

Monoaminergic neurotoxins

Dopaminergic|

* 2′-CH3-MPTP (2′-methyl-MPTP)
* 2,4,5-THA
* 2,4,5-THMA
* 4-MMA
* 5-S-Cysteinyldopamine
* 5,6-DHT
* 6-Hydroxydopa
* 6-OHDA quinone
* 6,7-DHT
* ALDH inhibitors (e.g., disulfiram, methylmercury)
* Amphetamine
* Benomyl
* Daidzin
* Dieldrin
* DOPA quinone
* DOPAL
* DOPAL quinone
* Dopamine
* Dopamine quinone
* Fenpropathrin
* Haloperidol
* HPP+
* HPTP
* Mancozeb
* Maneb
* Mephedrone
* Methamphetamine
* Methcathinone
* Methylone
* MPP+ (cyperquat)
* MPTP
* N-Methylnorsalsolinol
* Norsalsolinol
* Oxidopamine (6-OHDA)
* Paraquat
* Rotenone
* Salsolinol
* Ziram

Noradrenergic|

* 2′-NH2-MPTP (2′-amino-MPTP)
* 2,4,5-THA
* 4,5-DHT
* 5,6-DHT
* 5,7-DHT
* 6-Hydroxydopa
* DOPEGAL
* DSP-4
* MDA (tenamfetamine)
* Oxidopamine (6-OHDA)
* Xylamine

Serotonergic|

* 2′-NH2-MPTP (2′-amino-MPTP)
* 2,4-DCA
* 2,4,5-THA
* 2,4,5-THMA
* 3-CA
* 3,4-DCA
* 4-CAB (α-ethyl-PCA)
* 4-CMA
* 4-HO-5-MeO-T
* 4,5-DHT
* 5-IAI
* 5-MAPB
* 5,6-DHT
* 5,7-DHT
* 6,7-DHT
* αET
* Fenfluramine
* Haloperidol
* HHA (α-methyldopamine)
* HHMA (α-methylepinine, α,N-dimethyldopamine)
* HPP+
* HPTP
* MBDB
* MDA (tenamfetamine)
* MDMA (midomafetamine)
* Mephedrone
* Methamphetamine
* Methylone
* Norfenfluramine
* PBA
* PBMA
* PCA
* PCMA
* PIA

Unsorted|

* 5-HIAL
* RHPP+
* RHPTP

See also: Receptor/signaling modulators • Adrenergics • Dopaminergics • Melatonergics • Serotonergics • Monoamine reuptake inhibitors • Monoamine releasing agents • Monoamine metabolism modulators
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