Effect of mirtazepine on the CYP2D activity in the primary culture of rat hepatocytes.

Journal Title: Pharmacological Reports - Year 2006, Vol 58, Issue 6

Abstract

Our previous studies carried out on rats showed that mirtazapine given intraperitoneally at a dose of 3 mg/kg, twice a day for two weeks, increased the activity of CYP2D measured as ethylmorphine O-deethylation in liver microsomes. The aim of the present work was to find out whether the mirtazapine-induced increase in the CYP2D activity observed in vivo is connected with the central action of mirtazapine or the drug acts directly on hepatocytes. For this purpose, we studied the influence of pharmacological concentrations of mirtazapine (0.1, 1.0, 10 muM for 96 h) on the activity of CYP2D measured as the rates of ethylmorphine O-deethylation and dextromethorphan O-demethylation in the primary culture of rat hepatocytes. Additionally, we tested the ability of CYP isoforms to catalyze ethylmorphine O-deethylation, using cDNA-expressed CYPs and CYP inhibitors applied to liver microsomes. The obtained results indicate that mirtazapine applied at pharmacological concentrations can moderately increase the activity of rat CYP2D in hepatocytes, and CYP2D2 isoform contributes mostly to this effect. Similar result was previously obtained after in vivo administered mirtazapine in liver microsomes, but not in brain microsomes, the latter containing mainly CYP2D4 isoform. Mirtazapine appears to act directly on hepatocytes and its effect does not seem to depend on the central pharmacological action of the antidepressant. CYP2D2 is the main isoform catalyzing ethylmorphine O-deethylation while CYP2A2, CYP2C6 and CYP2C11 are of minor importance.

Authors and Affiliations

Anna Haduch, Ewa Bromek, Marta Kot, Katalin Jemnitz, Zsuzsa Veres, László Vereczkey, Władysława Daniel

Keywords

Related Articles

Drug-induced myopathies. An overview of the possible mechanisms.

Myopathy is usually a non-fatal muscle disease involving skeletal muscle weakness, tenderness and pain with the possibility of the plasma creatinine kinase elevation. There are many different types of myopathies, some of...

BDNF and VEGF in the pathogenesis of stress-induced affective diseases: An insight from experimental studies.

Stress is known to play an important role in etiology, development and progression of affective diseases. Especially, chronic stress, by initiating changes in the hypothalamic-pituitary-adrenal axis (HPA), neurotransmiss...

Drug therapy in autism: a present and future perspective.

Autism is a neurodevelopmental disorder, with a multifactorial etiology, characterized by severe abnormalities in communications, social awareness and skills, and the presence of restrictive and stereotyped patterns of b...

Pleiotropic effects of angiotensin-converting enzyme inhibitors in normotensive patients with coronary artery disease.

Angiotensin-converting enzyme inhibitors proved to be effective in the primary and secondary prevention of cardiovascular diseases. Clinical effectiveness of this group of agents may largely depend on their pleiotropic e...

Cerivastatin and hypercholesterolemia reduce apoptosis of cardiomyocytes in guinea pig papillary muscle subjected to hypoxia/reoxygenation.

The aim of this study was to assess how cerivastatin influences contractility and degree of myocardial damage in papillary muscle subjected to hypoxia-reoxygenation in hypercholesterolemic guinea pigs. Study group consis...

Download PDF file
  • EP ID EP112849
  • DOI -
  • Views 119
  • Downloads 0

How To Cite

Anna Haduch, Ewa Bromek, Marta Kot, Katalin Jemnitz, Zsuzsa Veres, László Vereczkey, Władysława Daniel (2006). Effect of mirtazepine on the CYP2D activity in the primary culture of rat hepatocytes.. Pharmacological Reports, 58(6), 979-984. https://europub.co.uk/articles/-A-112849