Cytochrome P450 Enzymatic Functions in Central Nervous System Metabolism

Cytochrome P450 (CYP) enzymes mediate a wide array of oxidative reactions that shape the chemical landscape of the central nervous system. Beyond their classical role in hepatic drug clearance, several CYP isoforms are expressed at the blood–brain barrier, within neurons, glia and the neurovascular unit. In the CNS they contribute to the local synthesis and degradation of neuroactive substances such as dopamine, serotonin and neurosteroids, influence the biotransformation of psychoactive drugs at their site of action and participate in detoxification of environmental chemicals. Spatial and temporal patterns of CYP expression, governed by genetic polymorphisms, developmental programmes and pathophysiological stimuli, underpin individual differences in drug response and vulnerability to neurotoxic insults. Emerging evidence has highlighted the importance of CYP-mediated pathways in tryptophan and steroid metabolism, the formation of neuromodulatory metabolites and the oxidative bioactivation of prodrugs. Understanding the regional distribution, substrate specificity and regulatory mechanisms of brain CYPs is essential for refining central nervous system pharmacokinetic models, optimising therapeutic strategies and minimising adverse effects in neuropsychiatric and neurodegenerative disorders.

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Cytochrome P450 Enzymatic Functions in Central Nervous System Metabolism publication trend

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Technical terms

Cytochrome P450: Heme‐containing monooxygenases that catalyse phase I oxidative metabolism of endogenous and exogenous compounds in the CNS and periphery.

Blood–brain barrier: Highly selective endothelial interface that controls the exchange of molecules between the systemic circulation and the central nervous system.

Neurosteroid: Steroid molecules synthesised within the brain that modulate neuronal ion channels and neurotransmitter receptors.

Xenobiotic: A chemical compound foreign to an organism’s normal biochemistry, including drugs, toxins and environmental pollutants.

References

1. Alterations of Cytochrome P450s and UDP-Glucuronosyltransferases in Brain Under Diseases and Their Clinical Significances. Frontiers in Pharmacology (2021).
2. Pharmacokinetic and pharmacodynamic studies of nicotine in rat brain: a simultaneous investigation of nicotine metabolites and the release of neurotransmitters in vivo. Frontiers in Chemistry (2023).
3. Pathophysiological implications of neurovascular P450 in brain disorders. Drug Discovery Today (2016).
4. The Engagement of Cytochrome P450 Enzymes in Tryptophan Metabolism. Metabolites (2023).