METABOLIC PROFILING OF HALOPERIDOL: INSIGHTS INTO POTENTIAL TOXICOLOGICAL EFFECTS ON BRAIN MICROVASCULAR ENDOTHELIAL CELLS

Abstract

Haloperidol is effective in the treatment of schizophrenia symptoms, but the adverse effects and overdose risks are significant. The metabolic consequences of haloperidol at high therapeutic doses, including the metabolites produced, remain only partially understood. To analyse endogenous cellular metabolites thoroughly, researchers can use untargeted metabolomics-based liquid chromatography-mass spectrometry. The aim of this approach is to reveal the potential toxic effects of high-dose haloperidol on brain microvascular endothelial cells (BMVECs) integral to the human blood-brain barrier. We identified 62 significant metabolites linked to the toxic response in BMVECs and pinpointed four haloperidol-related processes: the pentose phosphate pathway; the citrate cycle; glutamine and glutamate metabolism; and alanine, aspartate and glutamate metabolism. Our findings clarify the metabolic effects of high-dose haloperidol, thereby providing insights for refining its clinical application and for further studies, personalized medicine and the development of novel therapeutic strategies.