Oxidative reactions and schizophrenia: A review-discussion

doi:10.1016/S0920-9964(97)00005-4

Schizophrenia Research

Volume 24, Issue 3, 11 April 1997, Pages 357-364

https://doi.org/10.1016/S0920-9964(97)00005-4 Get rights and content

Abstract

Now that definitive direct evidence has been obtained that oxidized metabolites of catecholamines — aminochrome (derived from dopamine) and related compounds — occur in the human brain the question this paper explores is what is their function there, if any. They are precursors of neuromelanin and are formed inter alia by co-oxidation by prostaglandin H synthase during the synthesis of prostaglandin H from arachidonic acid. Their further metabolism by NAHPD-cytochrome P450 reductase forms the highly neurotoxic o-semiquinone together with free oxygen radicals. The defenses against these orthoquinones (o-quinones) and o-semiquinones (which include reduction, O-methylation, 5-cysteinylization, glutathione conjugation, conversion to the o-hydroquinone, and neuromelanin formation), and their possible status in schizophrenia, are reviewed. This system is closely linked with glutamate neurotoxicity because glutamate receptors activate PGH synthase and because dopamine toxicity is mediated by these o-quinones acting on NMDA receptors. Interactions between glutamate and dopamine neurotoxicity are explored, including a possible role for the redox properties of catecholamines. The hypothesis is presented that some of the demonstrated cellular damage in the schizophrenic brain may be mediated by catecholamine o-quinones. The significance of the evidence from previous studies carried out 40 years ago, that a closely related catecholamine o-quinone — adrenochrome — has psychotomimetic properties in humans and behavior disrupting properties in animals, is reviewed in the light of these recent findings.

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Oxidative reactions and schizophrenia: A review-discussion

Abstract

Brain Res.

Bicohem. Mol. Med.

Biol. Psychiatry

Biol. Psychiatry

Psychiat. Res.

Neurosci. Biobehav. Rev.

Biochim. Biophys. Acta

Brain Res.

Neurochem. Int.

Biol. Psychiatry

Curr. Op. Neurobiol.

TINS

Psychiat. Res.

J. Psychiat. Res.

Biochem. Pharmacol.

Psychiat. Res.

Prog. Neurobiol.

Exp. Neurol.

Brain Res.

Schizophr. Res.

J. Mol. Cell. Cardiol.

Neurochem. Int.

Exp. Neurol.

Biol. Psychiatry

Neuron

Prog. Neurosci.

Biol. Psychiatry

TINS

Neuroscience

Biochem. Mol. Med.

Chem. Biol. Interact.

Brain Res.

Neuron

Anal. Biochem.

Biol Psychiatry

Int. J. Neuropharmacol.

Neuron

Activities of superoxide dismutase and glutathione peroxidase in schizophrenics and manic-depressive patients

Clin. Chem.

Cyclooxygenase-2 induction in cerebral cortex: an intracellular response to synaptic excitation

J. Neurochem.

The catecholaminergic innervation of the human entorhinal cortex: alteration in schizophrenia

Abstr. Soc. Neurosci.

Regulation of the final phase of mammalian melanogenesis

Eur. J. Biochem.

Hydroxyl radical formation during apoptosis induced by 2'-methyl-MPTP in PC12 cells

FASEB J.

The monoamine innervation of rat cerebral cortex: synaptic and non-synaptic terminals

Neuroscience

Dopamine neurotoxicity: inhibition of mitochondrial respiration

J. Neurochem.