A monoamine neurotoxin, or monoaminergic neurotoxin, is a drug that selectively damages or destroys monoaminergic neurons. 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), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and methamphetamine; and the noradrenergic neurotoxins oxidopamine and N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (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. 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.
Dopaminergic neurotoxins can induce a Parkinson's disease-like condition in animals and humans. Serotonergic neurotoxins like MDMA have been associated with cognitive and memory deficits and psychiatric changes.
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) 3,4-Dichloroamphetamine (3,4-DCA) 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) 3,4-Methylenedioxymethamphetamine (MDMA) 4-Chlorophenylisobutylamine (4-CAB; 4-chloro-α-desmethyl-α-ethylamphetamine; α-ethyl-PCA) 5-MAPB Fenfluramine Mephedrone Methamphetamine Methylbenzodioxolylbutanamine (MBDB) Methylone Norfenfluramine para-Bromoamphetamine (PBA; 4-bromoamphetamine; 4-BA) para-Bromomethamphetamine (PBMA; 4-bromomethamphetamine; 4-BMA) para-Chloroamphetamine (PCA; 4-chloroamphetamine; 4-CA) para-Chloromethamphetamine (PCMA; 4-chloromethamphetamine; 4-PCMA) para-Iodoamphetamine (PIA; 4-iodoamphetamine; 4-IA)
Tryptamines 4-Hydroxy-5-methoxytryptamine (4-HO-5-MeO-T) 4,5-Dihydroxytryptamine (4,5-DHT) 5-MeO-DiPT (5-methoxy-N,N-diisopropyltryptamine) 5,6-Dihydroxytryptamine (5,6-DHT) 5,7-Dihydroxytryptamine (5,7-DHT) 6,7-Dihydroxytryptamine (6,7-DHT) α-Ethyltryptamine (αET)
2-Aminoindans 5-Iodo-2-aminoindane (5-IAI) (weak) 5-Methoxy-6-methyl-2-aminoindane (MMAI) (weak; alone and with amphetamine) 5,6-Methylenedioxy-2-aminoindane (MDAI) (weak; alone and with amphetamine) N-Ethyl-5-trifluoromethyl-2-aminoindane (ETAI) 5-Trifluoromethyl-2-aminoindane (TAI)
MPTP-related 2′-NH2-MPTP (2′-amino-MPTP) Haloperidol HPP+ (haloperidol pyridinium) HPTP
Dopaminergic neurotoxins Phenethylamines 2,4,5-Trihydroxyamphetamine (2,4,5-THA) 2,4,5-Trihydroxymethamphetamine (2,4,5-THMA) 3,4-Methylenedioxymethamphetamine (MDMA) (in mice but not in humans) 4-Methylmethamphetamine (4-MMA; mephedrine) 6-Hydroxydopa (6-OH-DOPA, 6-OHDOPA) 6-Hydroxydopamine quinone (6-OHDA quinone; oxidopamine quinone) Amphetamine Mephedrone Methamphetamine Methcathinone Methylone Oxidopamine (6-hydroxydopamine; 6-OHDA)
Dopamine and metabolites 3,4-Dihydroxyphenylacetaldehyde (DOPAL; dopamine aldehyde) 5-S-Cysteinyldopamine (5-S-CyS-DA) DOPA quinone DOPAL quinone Dopamine Dopamine quinone N-Methylnorsalsolinol Norsalsolinol Salsolinol
Tryptamines 5,6-Dihydroxytryptamine (5,6-DHT) 6,7-Dihydroxytryptamine (6,7-DHT) 1-Trichloromethyl-1,2,3,4-tetrahydro-β-carboline (TaClo; 1-TCMTC)
MPTP-related 2′-CH3-MPTP (2′-methyl-MPTP) Haloperidol HPP+ (haloperidol pyridinium) HPTP MPP+ (cyperquat) MPTP
Pesticides Benomyl Daidzin Dieldrin Fenpropathrin Mancozeb Maneb Paraquat Rotenone Ziram
Others Aldehyde dehydrogenase (ALDH) inhibitors (e.g., disulfiram, methylmercury) Imidazole propionate (ImP)
Noradrenergic neurotoxins Phenethylamines and related 2,4,5-Trihydroxyamphetamine (2,4,5-THA) 3,4-Methylenedioxyamphetamine (MDA) 3,4-Dihydroxyphenylglycolaldehyde (DOPEGAL; norepinephrine/epinephrine aldehyde) 6-Hydroxydopa (6-OH-DOPA, 6-OHDOPA) DSP-4 Oxidopamine (6-hydroxydopamine; 6-OHDA) Xylamine
Tryptamines and related 4,5-Dihydroxytryptamine (4,5-DHT) 5,6-Dihydroxytryptamine (5,6-DHT) 5,7-Dihydroxytryptamine (5,7-DHT)
MPTP-related 2′-NH2-MPTP (2′-amino-MPTP)
Unsorted or unknown 2,5-DDM-DOM 5-Hydroxyindoleacetaldehyde (5-HIAL) RHPP+ RHPTP
See also Monoamine-depleting agent
References