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Haloperidol
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=== Potential neurotoxicity === Several lines of evidence suggest that haloperidol exhibits [[neurotoxicity]].<ref name="pmid28738100">{{cite journal | vauthors = Nasrallah HA, Chen AT | title = Multiple neurotoxic effects of haloperidol resulting in neuronal death | journal = Annals of Clinical Psychiatry | volume = 29 | issue = 3 | pages = 195–202 | date = August 2017 | pmid = 28738100 | doi = }}</ref><ref>{{cite journal | vauthors = Pierre JM | title = Time to retire haloperidol? | journal = Current Psychiatry | volume = 19 | issue = 5 | page = 19 | url = https://www.mdedge.com/psychiatry/article/221293/schizophrenia-other-psychotic-disorders }}</ref> Some studies report an association between antipsychotic medications, especially first-generation agents, and a decline in [[gray matter]] volume.<ref>Id.</ref> Haloperidol irreversibly blocks the [[sigma receptor|sigma]] [[sigma-1 receptor|σ<sup>1</sup> receptor]].<ref>{{cite journal | vauthors = Cobos EJ, del Pozo E, Baeyens JM | title = Irreversible blockade of sigma-1 receptors by haloperidol and its metabolites in guinea pig brain and SH-SY5Y human neuroblastoma cells | journal = Journal of Neurochemistry | volume = 102 | issue = 3 | pages = 812–825 | date = August 2007 | pmid = 17419803 | doi = 10.1111/j.1471-4159.2007.04533.x }}</ref> It may exert deleterious effects on the [[dorsolateral prefrontal cortex]] (DLPFC) by attenuating [[brain-derived neurotrophic factor]] (BDNF) transcription and expression, associated with an increase in the long non-coding RNA BDNF-AS in the DLPFC.<ref name="pmid36816400">{{cite journal | vauthors = Hemby SE, McIntosh S | title = Chronic haloperidol administration downregulates select BDNF transcript and protein levels in the dorsolateral prefrontal cortex of rhesus monkeys | journal = Frontiers in Psychiatry | volume = 14 | issue = | pages = 1054506 | date = 2023 | pmid = 36816400 | pmc = 9932326 | doi = 10.3389/fpsyt.2023.1054506 | doi-access = free }}</ref> Besides the preceding mechanisms, haloperidol metabolizes into [[HPP+|HPP<sup>+</sup>]], a [[monoaminergic neurotoxin]] related to [[MPTP]].<ref name="Kostrzewa2022" /><ref name="Igarashi1998" /><ref name="GórskaMarszałłSloderbach2015" /> This might be involved in the [[extrapyramidal symptoms]] that develop with long-term haloperidol therapy.<ref name="Kostrzewa2022" /><ref name="Igarashi1998" /><ref name="GórskaMarszałłSloderbach2015" />
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