Are Dopamine, Norepinephrine, and Serotonin Precursors of Biologically Reactive Intermediates Involved in the Pathogenesis of Neurodegenerative Brain Disorders?

  • Glenn Dryhurst
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 500)


During the past two or three decades an immense amount of research has been carried out to understand the fundamental molecular mechanisms that underlie the neurotoxicity evoked by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), methamphetamine (MA) and related amphetamine drugs of abuse. The neurotoxicity of MPTP is of particular interest because it not only mimics the symptoms and major pathobiochemical changes that occur in Parkinson’s disease (PD) but also arguably provides the best model of PD in animals (Gerlach et al.,1991; Gerlach and Riederer, 1996; Royland and Langston, 1998). Interest in the neurotoxicity evoked by MA derives not only from the fact that this compound is a widely abused psychoactive drug but in animals it also mimics many of the major pathobiochemical changes that occur in PD (Gerlach and Riederer, 1996) although it is a less selective neurotoxin than MPTP. Transient cerebral ischemia, or ischemia-reperfusion (I-R), can also lead to neurodegeneration although this is even less selective than MA. Nevertheless, there are a rather striking number of similar factors that appear to be key steps in a complex cascade of processes that compromise the neurotoxic mechanisms evoked by MPTP, MA and I-R. In this communication similarities associated with the neurotoxicity evoked by MPTP, MA and I-R will be briefly reviewed. Subsequently, these will be integrated into a working hypothesis for the underlying neurotoxic mechanisms in which one or more of the neurotransmitters dopamine (DA), norepinephrine (NE) and 5-hydroxytryptamine (5-HT; serotonin) are proposed to be the precursors of biologically reactive intermediates in the pathological processes.


Transient Cerebral Ischemia Energy Impairment Dopaminergic Neurotoxicity Neurotoxic Mechanism Selective Neurotoxin 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Glenn Dryhurst
    • 1
  1. 1.Department of Chemistry and BiochemistryUniversity of OklahomaNormanUSA

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