Monoamine 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]

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

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

Serotonergic neurotoxins

Phenethylamines

• 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

• 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

• 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

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

Dopaminergic neurotoxins

Phenethylamines

• 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

• 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

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

MPTP-related

• 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

• 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

• Aldehyde dehydrogenase (ALDH) inhibitors (e.g., disulfiram, methylmercury)^{[71][78][79][80]}

Noradrenergic neurotoxins

Phenethylamines and related

• 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

• 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

• 2′-NH₂-MPTP (2′-amino-MPTP)^[1]

Unsorted or unknown

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

See also

• Monoamine-depleting agent