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 like MDMA have been associated with cognitive and memory deficits and psychiatric changes.^{[8][9][10][11][12]}

List of monoamine neurotoxins

Serotonergic neurotoxins

Phenethylamines

• 2,4-Dichloroamphetamine (2,4-DCA)^[13]
• 2,4,5-Trihydroxyamphetamine (2,4,5-THA)^[14]
• 2,4,5-Trihydroxymethamphetamine (2,4,5-THMA)^[14]
• 3-Chloroamphetamine (3-CA)^[13][15]
• 3,4-Dichloroamphetamine (3,4-DCA)^[13]
• 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][16][2][14]}
• 3,4-Methylenedioxyethylamphetamine (MDEA)^[16][17]
• 3,4-Methylenedioxymethamphetamine (MDMA)^{[1][2][18][19]}
• 4-Chlorophenylisobutylamine (4-CAB; 4-chloro-α-desmethyl-α-ethylamphetamine; α-ethyl-PCA)^[16]
• 5-MAPB^[20]
• Fenfluramine^{[1][21][22][23]}
• Mephedrone^[24]
• Methamphetamine^[1][19][14]
• Methylbenzodioxolylbutanamine (MBDB)^[16][17]
• Methylone^[24]
• Norfenfluramine^[23][25]
• para-Bromoamphetamine (PBA; 4-bromoamphetamine; 4-BA)^[26]
• para-Bromomethamphetamine (PBMA; 4-bromomethamphetamine; 4-BMA)^[27][28]
• para-Chloroamphetamine (PCA; 4-chloroamphetamine; 4-CA)^[1][2][17]
• para-Chloromethamphetamine (PCMA; 4-chloromethamphetamine; 4-PCMA)^[13][29]
• para-Iodoamphetamine (PIA; 4-iodoamphetamine; 4-IA)^[16][30]

Tryptamines

• 4-Hydroxy-5-methoxytryptamine (4-HO-5-MeO-T)^[31][32]
• 4,5-Dihydroxytryptamine (4,5-DHT)^[33][34][32]
• 5-MeO-DiPT (5-methoxy-N,N-diisopropyltryptamine)^{[35][36][37][38][39]}
• 5,6-Dihydroxytryptamine (5,6-DHT)^[40][1][2]
• 5,7-Dihydroxytryptamine (5,7-DHT)^[40][1][2]
• 6,7-Dihydroxytryptamine (6,7-DHT)^[33][41]
• α-Ethyltryptamine (αET)^[17][42][43]

2-Aminoindans

• 5-Iodo-2-aminoindane (5-IAI) (weak)^[44][17][16]
• 5-Methoxy-6-methyl-2-aminoindane (MMAI) (weak; alone and with amphetamine)^[45][46][47]
• 5,6-Methylenedioxy-2-aminoindane (MDAI) (weak; alone and with amphetamine)^[48][16][49]
• N-Ethyl-5-trifluoromethyl-2-aminoindane (ETAI)^[50]
• 5-Trifluoromethyl-2-aminoindane (TAI)^[50]

MPTP-related

• 2′-NH₂-MPTP (2′-amino-MPTP)^[1]
• Haloperidol^[1][51]
• HPP⁺ (haloperidol pyridinium)^[1][51]
• HPTP^[1][52]

Dopaminergic neurotoxins

Phenethylamines

• 2,4,5-Trihydroxyamphetamine (2,4,5-THA)^[14]
• 2,4,5-Trihydroxymethamphetamine (2,4,5-THMA)^[14]
• 3,4-Methylenedioxymethamphetamine (MDMA) (in mice but not in humans)^[19][10]
• 4-Methylmethamphetamine (4-MMA; mephedrine)^[53][54]
• 6-Hydroxydopa (6-OH-DOPA, 6-OHDOPA)^[1][55][56]
• 6-Hydroxydopamine quinone (6-OHDA quinone; oxidopamine quinone)^[57][58]
• Amphetamine^[1]
• Mephedrone^[24]
• Methamphetamine^[1][18][19]
• Methcathinone^[53][54]
• Methylone^[24]
• Oxidopamine (6-hydroxydopamine; 6-OHDA)^[59][60][57]

Dopamine and metabolites

• 3,4-Dihydroxyphenylacetaldehyde (DOPAL; dopamine aldehyde)^[61][62]
• 5-S-Cysteinyldopamine (5-S-CyS-DA)^[63]
• DOPA quinone^[64][65]
• DOPAL quinone^[66]
• Dopamine^[67]
• Dopamine quinone^[64][65]
• N-Methylnorsalsolinol^[68]
• Norsalsolinol^[68]
• Salsolinol^[68][69]

Tryptamines

• 5,6-Dihydroxytryptamine (5,6-DHT)^[40][70]
• 6,7-Dihydroxytryptamine (6,7-DHT)^[33][41]

MPTP-related

• 2′-CH₃-MPTP (2′-methyl-MPTP)^{[71][72][73][74][75]}
• Haloperidol^[1][51]
• HPP⁺ (haloperidol pyridinium)^[1][51]
• HPTP^[1][52]
• MPP⁺ (cyperquat)^[76][77]
• MPTP^[76]

Pesticides

• Benomyl^[78]
• Daidzin^[78]
• Dieldrin^[78]
• Fenpropathrin^[79][80][81]
• Mancozeb^[82]
• Maneb^[82]
• Paraquat^[79][82][83]
• Rotenone^{[1][79][82][84]}
• Ziram^[78]

Others

• Aldehyde dehydrogenase (ALDH) inhibitors (e.g., disulfiram, methylmercury)^{[78][85][86][87]}

Noradrenergic neurotoxins

Phenethylamines and related

• 2,4,5-Trihydroxyamphetamine (2,4,5-THA)^[14]
• 3,4-Methylenedioxyamphetamine (MDA)^[14]
• 3,4-Dihydroxyphenylglycolaldehyde (DOPEGAL; norepinephrine/epinephrine aldehyde)^[88]
• 6-Hydroxydopa (6-OH-DOPA, 6-OHDOPA)^[1][55][56]
• DSP-4^[89][90]
• Oxidopamine (6-hydroxydopamine; 6-OHDA)^[59][57]
• Xylamine^[1]

Tryptamines and related

• 4,5-Dihydroxytryptamine (4,5-DHT)^[33][34]
• 5,6-Dihydroxytryptamine (5,6-DHT)^[40][70]
• 5,7-Dihydroxytryptamine (5,7-DHT)^[40][70]

MPTP-related

• 2′-NH₂-MPTP (2′-amino-MPTP)^[1]

Unsorted or unknown

• 5-Hydroxyindoleacetaldehyde (5-HIAL)^[91][92][93]
• RHPP^+[94][52]
• RHPTP^{[95][96][97][98]}

See also

• Monoamine-depleting agent