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]
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]
Dopaminergic neurotoxins can induce a Parkinson's disease-like condition in animals and humans.[1][5] Serotonergic neurotoxins have been associated with cognitive and memory deficits and psychiatric changes.[6][7][8][9]
List of monoamine neurotoxins
[edit]Serotonergic neurotoxins
[edit]Phenethylamines
[edit]- 2,4-Dichloroamphetamine (2,4-DCA)[10]
- 2,4,5-Trihydroxyamphetamine (2,4,5-THA)[11]
- 2,4,5-Trihydroxymethamphetamine (2,4,5-THMA)[11]
- 3-Chloroamphetamine (3-CA)[10][12]
- 3,4-Dichloroamphetamine (3,4-DCA)[10]
- 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][13][2][11]
- 3,4-Methylenedioxyethylamphetamine (MDEA)[13][14]
- 3,4-Methylenedioxymethamphetamine (MDMA)[1][2][15][16]
- 4-Chlorophenylisobutylamine (4-CAB; 4-chloro-α-desmethyl-α-ethylamphetamine; α-ethyl-PCA)[13]
- 5-MAPB[17]
- Fenfluramine[1][18][19][20]
- Mephedrone[21]
- Methamphetamine[1][16][11]
- Methylbenzodioxolylbutanamine (MBDB)[13][14]
- Methylone[21]
- Norfenfluramine[20][22]
- para-Bromoamphetamine (PBA; 4-bromoamphetamine; 4-BA)[23]
- para-Chloroamphetamine (PCA; 4-chloroamphetamine; 4-CA)[1][2][14]
- para-Chloromethamphetamine (PCMA; 4-chloromethamphetamine; 4-PCMA)[10][24]
- para-Iodoamphetamine (PIA; 4-iodoamphetamine; 4-IA)[13][25]
Tryptamines
[edit]- 4,5-Dihydroxytryptamine (4,5-DHT)[26][27]
- 5,6-Dihydroxytryptamine (5,6-DHT)[28][1][2]
- 5,7-Dihydroxytryptamine (5,7-DHT)[28][1][2]
- 6,7-Dihydroxytryptamine (6,7-DHT)[26][29]
- α-Ethyltryptamine (αET)[14][30][31]
2-Aminoindans
[edit]- 5-Iodo-2-aminoindan (5-IAI) (weak)[32][14][13]
- 5-Methoxy-6-methyl-2-aminoindane (MMAI) (weak; alone and with amphetamine)[33][34][35]
- 5,6-Methylenedioxy-2-aminoindan (MDAI) (weak; alone and with amphetamine)[36][13][37]
MPTP-related
[edit]Dopaminergic neurotoxins
[edit]Phenethylamines
[edit]- 2,4,5-Trihydroxyamphetamine (2,4,5-THA)[11]
- 2,4,5-Trihydroxymethamphetamine (2,4,5-THMA)[11]
- 3,4-Methylenedioxymethamphetamine (MDMA) (in mice but not in humans)[16][8]
- 6-Hydroxydopa (6-OH-DOPA, 6-OHDOPA)[1][40][41]
- 6-Hydroxydopamine quinone (6-OHDA quinone; oxidopamine quinone)[42][43]
- Amphetamine[1]
- Mephedrone[21]
- Methamphetamine[1][15][16]
- Methylone[21]
- Oxidopamine (6-hydroxydopamine; 6-OHDA)[44][45][42]
Dopamine and metabolites
[edit]- 3,4-Dihydroxyphenylacetaldehyde (DOPAL; dopamine aldehyde)[46][47]
- 5-S-Cysteinyldopamine (5-S-CyS-DA)[48]
- DOPA quinone[49][50]
- DOPAL quinone[51]
- Dopamine[52]
- Dopamine quinone[49][50]
- N-Methylnorsalsolinol[53]
- Norsalsolinol[53]
- Salsolinol[53][54]
Tryptamines
[edit]- 5,6-Dihydroxytryptamine (5,6-DHT)[28][55]
- 6,7-Dihydroxytryptamine (6,7-DHT)[26][29]
MPTP-related
[edit]- 2′-CH3-MPTP (2′-methyl-MPTP)[56][57][58][59][60]
- Haloperidol[1][38]
- HPP+ (haloperidol pyridinium)[1][38]
- HPTP[1][39]
- MPP+ (cyperquat)[61][62]
- MPTP[61]
Pesticides
[edit]- Benomyl[63]
- Daidzin[63]
- Dieldrin[63]
- Fenpropathrin[64][65][66]
- Mancozeb[67]
- Maneb[67]
- Paraquat[64][67][68]
- Rotenone[1][64][67][69]
- Ziram[63]
Others
[edit]Noradrenergic neurotoxins
[edit]Phenethylamines and related
[edit]- 2,4,5-Trihydroxyamphetamine (2,4,5-THA)[11]
- 3,4-Methylenedioxyamphetamine (MDA)[11]
- 3,4-Dihydroxyphenylglycolaldehyde (DOPEGAL; norepinephrine/epinephrine aldehyde)[73]
- 6-Hydroxydopa (6-OH-DOPA, 6-OHDOPA)[1][40][41]
- DSP-4[74][75]
- Oxidopamine (6-hydroxydopamine; 6-OHDA)[44][42]
- Xylamine[1]
Tryptamines and related
[edit]- 4,5-Dihydroxytryptamine (4,5-DHT)[26][27]
- 5,6-Dihydroxytryptamine (5,6-DHT)[28][55]
- 5,7-Dihydroxytryptamine (5,7-DHT)[28][55]
MPTP-related
[edit]- 2′-NH2-MPTP (2′-amino-MPTP)[1]
Unsorted or unknown
[edit]See also
[edit]References
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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.
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Ironically, in the 1960s, MPP+ itself had been tested as an herbicide under the commercial name of cyperquat (Di Monte, 2001).
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