Monoamine neurotoxin

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]

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]

  1. ^ a b c d Kostrzewa RM (2022). "Survey of Selective Monoaminergic Neurotoxins Targeting Dopaminergic, Noradrenergic, and Serotoninergic Neurons". Handbook of Neurotoxicity. Cham: Springer International Publishing. pp. 159–198. doi:10.1007/978-3-031-15080-7_53. ISBN 978-3-031-15079-1.
  2. ^ Cite error: The named reference BaumgartenLachenmayer2004 was invoked but never defined (see the help page).
  3. ^ a b Baggott M, Mendelson J (2001). "Does MDMA Cause Brain Damage?". In Holland J (ed.). Ecstasy: The Complete Guide: A Comprehensive Look at the Risks and Benefits of MDMA. Inner Traditions/Bear. pp. 110–145, 396–404. ISBN 978-0-89281-857-0. Retrieved 24 November 2024. 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.
  4. ^ a b Sprague JE, Everman SL, Nichols DE (June 1998). "An integrated hypothesis for the serotonergic axonal loss induced by 3,4-methylenedioxymethamphetamine" (PDF). Neurotoxicology. 19 (3): 427–441. PMID 9621349.
  5. ^ Grünblatt E, Mandel S, Youdim MB (April 2000). "MPTP and 6-hydroxydopamine-induced neurodegeneration as models for Parkinson's disease: neuroprotective strategies". J Neurol. 247 (Suppl 2): II95–102. doi:10.1007/pl00022909. PMID 10991672.
  6. ^ Parrott AC (April 2002). "Recreational Ecstasy/MDMA, the serotonin syndrome, and serotonergic neurotoxicity". Pharmacol Biochem Behav. 71 (4): 837–844. doi:10.1016/s0091-3057(01)00711-0. PMID 11888574.
  7. ^ Parrott AC (September 2013). "MDMA, serotonergic neurotoxicity, and the diverse functional deficits of recreational 'Ecstasy' users". Neurosci Biobehav Rev. 37 (8): 1466–1484. doi:10.1016/j.neubiorev.2013.04.016. PMID 23660456.
  8. ^ Cite error: The named reference AguilarGarcía-PardoParrott2020 was invoked but never defined (see the help page).
  9. ^ Montgomery C, Roberts CA (January 2022). "Neurological and cognitive alterations induced by MDMA in humans" (PDF). Exp Neurol. 347: 113888. doi:10.1016/j.expneurol.2021.113888. PMID 34624331.