Autoinduction of the metabolism of phenothiazine neuroleptics in a primary culture of human hepatocytes.
Journal Title: Pharmacological Reports - Year 2012, Vol 64, Issue 6
Abstract
BACKGROUND: The metabolism of phenothiazine neuroleptics (promazine, perazine) in a primary culture of human hepatocytes after pretreatment of cells with those neuroleptics was studied. METHODS: The hepatocytes were pretreated with 25 μM promazine or perazine for 96 h. Then, the cells were incubated for 2, 4, 6, 8 and 24 h in the presence of neuroleptics. At the indicated time points, concentrations of phenothiazines and their metabolites (5-sulfoxides and N-desmethyl derivatives) were measured in the culture medium using HPLC with UV detection. Results: Pretreatment of the primary culture of human hepatocytes with promazine or perazine resulted in accumulation of their metabolites in the culture medium. Such an effect was not observed in the case of control cultures (not pretreated with neuroleptics). Conclusion: The obtained results suggest that the tested phenothiazines may stimulate their own metabolism by inducing CYP1A2, CYP3A4 and CYP2C19 isoforms.
Authors and Affiliations
Jacek Wójcikowski, Patrick Maurel, Władysława Daniel
Keywords
Related Articles
- EP ID EP93249
- DOI -
- Views 125
- Downloads 0
Endothelial dysfunction in pre-eclampsia.
The repeated demonstration of biomarkers of endothelial cell and leukocyte activation has suggested that the maternal syndrome of pre-eclampsia arises from a generalised maternal inflammatory systemic response incorporat...
Advanced glycation and retinal pathology during diabetes.
Of all microvascular complications of diabetes mellitus, retinopathy remains the most common. This disease presents major therapeutic problems for the ophthalmologist and despite many decades of intense research it still...
Influence of bupropion and calcium channel antagonists on the nicotine-induced memory-related response of mice in the elevated plus maze.
In this study, we investigated the effects of acute administration of nicotine on memory-related behavior in mice using the elevated plus maze test. In this test, the time necessary for mice to move from the open arm to...
A carbon monoxide-releasing molecule (CORM-3) attenuates lipopolysaccharide- and interferon-gamma-induced inflammation in microglia.
The development of carbon monoxide-releasing molecules (CO-RMs) in recent years helped to shed more light on the diverse range of anti-inflammatory and cytoprotective activities of CO gas. In this study, we examined the...
Third-generation antiepileptic drugs: mechanisms of action, pharmacokinetics and interactions.
This review briefly summarizes the information on the molecular mechanisms of action, pharmacokinetic profiles and drug interactions of novel (third-generation) antiepileptic drugs, including brivaracetam, carabersat, ca...