Biochemical and Biophysical Research Communications
Identification of potentially neurotoxic pyridinium metabolite in the urine of schizophrenic patients treated with haloperidol
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Rat brain CYP2D enzymatic metabolism alters acute and chronic haloperidol side-effects by different mechanisms
2017, Progress in Neuro-Psychopharmacology and Biological PsychiatryCitation Excerpt :The relationship between genotype and acute parkinsonism is less clear. Some CYP2D-mediated antipsychotic metabolites are potentially neurotoxic (Subramanyam et al., 1991; Subramanyam et al., 1990), but the relative roles of the parent and metabolites in side-effects are unknown. While brain DRD2 occupancy and resulting antipsychotic efficacy are closely related, they are not necessarily related to antipsychotic plasma levels (Tauscher et al., 2002), and this disconnect, taken with other risk factors for tardive dyskinesia, such as gender, age and length of illness, make it difficult to identify sources of inter-individual variation in risk for side-effects.
Brain levels of the neurotoxic pyridinium metabolite HPP+ and extrapyramidal symptoms in haloperidol-treated mice
2013, NeuroToxicologyCitation Excerpt :Therefore, it is plausible that HPP+ contributes to the pathophysiological effects of haloperidol via toxicity similar to that of MPP+. Consistent with this notion, HPP+ is found in post-mortem brain tissue, plasma and urine from patients with schizophrenia chronically treated with haloperidol (Eyles et al., 1994, 1997; Avent et al., 1997; Subramanyam et al., 1991). A positive relationship between the severity of TD and peripheral blood levels of HPP+ has been reported by two studies of a total of 51 haloperidol-treated patients (Iwahashi et al., 2001; Ulrich et al., 2005).
Identification of a butyrophenone analog as a potential atypical antipsychotic agent: 4-[4-(4-Chlorophenyl)-1,4-diazepan-1-yl]-1-(4-fluorophenyl)butan-1-one
2008, Bioorganic and Medicinal ChemistryMitochondriotropics: A review of their mode of action, and their applications for drug and DNA delivery to mammalian mitochondria
2007, Journal of Controlled ReleaseEffects of haloperidol and its pyridinium metabolite on plasma membrane permeability and fluidity in the rat brain
2007, Progress in Neuro-Psychopharmacology and Biological PsychiatryEvaluation of the eutomer of 4-{3-(4-chlorophenyl)-3-hydroxypyrrolidin-1-yl}-1-(4-fluorophenyl)butan- 1-one, {(+)-SYA 09}, a pyrrolidine analog of haloperidol
2006, Bioorganic and Medicinal Chemistry Letters