Direct and indirect interactions between antidepressant drugs and CYP2C6 in the rat liver during long-term treatment.

The aim of the present study was to investigate the influence of tricyclic antidepressants (TADs: imipramine, amitriptyline, clomipramine, desipramine), selective serotonin reuptake inhibitors (SSRIs: fluoxetine, sertraline) and novel antidepressant drugs (mirtazapine, nefazodone) on the activity of CYP2C6 measured as a rate of warfarin 7-hydroxylation. The reaction was studied in control liver microsomes in the presence of the antidepressants, as well as in microsomes of rats treated intraperitoneally (i.p.

The contribution of cytochrome P-450 isoenzymes to the metabolism of phenothiazine neuroleptics.

The aim of the present study was to determine optimum conditions for studying promazine and perazine metabolism in rat liver microsomes, and to investigate the influence of specific cytochrome P-450 inhibitors on 5-sulfoxidation and N-demethylation of these neuroleptics. Based on the developed method, the metabolism of neuroleptics in liver microsomes was studied at linear dependence of product formation on time, and protein and substrate concentrations (incubation time: 10 min; concentration of microsomal proteins: promazine-0.7 mg ml(-1), perazine-0.

Effects of antidepressant drugs on the activity of cytochrome P-450 measured by caffeine oxidation in rat liver microsomes.

Caffeine is a marker drug for testing the activity of CYP1A2 (3-N-demethylation) in humans and rats. Moreover, it is also a relatively specific substrate of CYP3A (8-hydroxylation). In the case of 1-N- and in particular 7-N-demethylation of caffeine, apart from CYP1A2, other cytochrome P-450 isoenzymes play a considerable role.

Effects of phenothiazine neuroleptics on the rate of caffeine demethylation and hydroxylation in the rat liver.

The primary metabolic pathways of caffeine are 3-N-demethylation to paraxanthine (CYP1A2), 1-N-demethylation to theobromine and 7-N-demethylation to theophylline (CYP1A2 and other enzymes), and 8-hydroxylation to 1,3,7-trimethyluric acid (CYP3A). The aim of the present study was to investigate the influence of phenothiazine neuroleptics (chlorpromazine, levomepromazine, thioridazine, perazine) on cytochrome P-450 activity measured by caffeine oxidation in rat liver microsomes. The obtained results showed that all the investigated neuroleptics competitively inhibited caffeine oxidation in the rat liver, though their potency to inhibit particular metabolic pathways was not equal.

The effect of selective serotonin reuptake inhibitors (SSRIs) on the pharmacokinetics and metabolism of perazine in the rat.

The aim of this study was to investigate the effect of three selective serotonin reuptake inhibitors (SSRIs), fluoxetine, fluvoxamine and sertraline, on the pharmacokinetics and metabolism of perazine in a steady state in rats. Perazine (10 mg kg(-1), i.p.

Different effects of amitriptyline and imipramine on the pharmacokinetics and metabolism of perazine in rats.

The aim of this study was to search for possible effects of imipramine and amitriptyline on the pharmacokinetics and metabolism of perazine at steady state in rats. Perazine (10 mg kg(-1), i.p.

Pharmacokinetics and metabolism of thioridazine during co-administration of tricyclic antidepressants.

1. Because of serious side-effects of thioridazine and tricyclic antidepressants (cardiotoxicity), a possible influence of imipramine and amitriptyline on the pharmacokinetics and metabolism of thioridazine was investigated in a steady state (2-week treatment) in rats. 2.

Effects of selective cytochrome P-450 inhibitors on the metabolism of thioridazine. In vitro studies.

The aim of the present study was to determine optimum conditions for the study of thioridazine metabolism in rat liver microsomes and to investigate the influence of specific cytochrome P-450 inhibitors on 2- and 5-sulfoxidation, and N-demethylation of thioridazine. Basing on the developed method, the thioridazine metabolism in liver microsomes was studied at linear dependence of the product formation on time, and protein and substrate concentrations (incubation time was 15 min, concentration of microsomal protein was 0.5 mg/ml, substrate concentrations were 25, 50 and 75 nmol/ml).

The influence of selective serotonin reuptake inhibitors (SSRIs) on the pharmacokinetics of thioridazine and its metabolites: in vivo and in vitro studies.

Due to its psychotropic profile, thioridazine is a neuroleptic suitable for a combination with antidepressants in a number of complex psychiatric illnesses. However, because of its serious side-effects, such a combination with selective serotonin reuptake inhibitors (SSRIs) which inhibit cytochrome P-450 may be dangerous. The aim of the present study was to investigate a possible impact of SSRIs on the pharmacokinetics and metabolism of thioridazine in a steady state in rats.

The influence of selective serotonin reuptake inhibitors on the plasma and brain pharmacokinetics of the simplest phenothiazine neuroleptic promazine in the rat.

The aim of the present study was to investigate a possible impact of the three selective serotonin reuptake inhibitors (SSRIs) fluoxetine, fluvoxamine and sertraline on the pharmacokinetics of promazine in a steady state in rats. Promazine was administered twice a day for 2 weeks, alone or jointly with one of the antidepressants. Concentrations of promazine and its two main metabolites (N-desmethylpromazine and sulfoxide) in the plasma and brain were measured at 30 min and 6 and 12 h after the last dose of the drugs.

Pharmacokinetics of phenothiazine neuroleptics after chronic coadministration of carbamazepine.

The aim of the present study was to assess the influence of carbamazepine on the pharmacokinetics of the two phenothiazine neuroleptics thioridazine and perazine in rats. The obtained results are compared with the results of analogical experiments concerning promazine. Thioridazine or perazine (10 mg/kg i.

Promazine pharmacokinetics during concurrent treatment with tricyclic antidepressants.

The aim of the present study was to search for a possible effect of tricyclic antidepressants on the pharmacokinetics of promazine. Male Wistar rats received promazine and/or an antidepressant (amitriptyline, imipramine) at a dose of 10 mg/kg i.p.

Pharmacokinetics of thioridazine and its metabolites in blood plasma and the brain of rats after acute and chronic treatment.

This study was aimed at investigation of the pharmacokinetics of thioridazine and its metabolites after a single and repeated administrations. Male Wistar rats received thioridazine as a single dose (10 mg/kg i.p.

Effect of carbamazepine on the pharmacokinetics of promazine.

Combinations of neuroleptics and carbamazepine are administered to psychiatric patients in the therapy of mania, manic-depressive illness and schizophrenia. The present study was aimed at assessing the influence of carbamazepine on the pharmacokinetics of promazine. Male Wistar rats received promazine and/or carbamazepine twice daily for two weeks (promazine, 10 mg/kg ip; carbamazepine, 15 mg/kg ip during the 1st, and 20 mg/kg ip during the 2nd week of treatment).

The pharmacokinetics of promazine and its metabolites after acute and chronic administration to rats--a comparison with the pharmacokinetics of imipramine.

This study was aimed to investigate the pharmacokinetics of promazine (a phenothiazine analogue of imipramine) after its single and repeated administration. Male Wistar rats received promazine as a single injection (10 mg/kg ip) or they were treated chronically with the neuroleptic, once a day for two weeks. Plasma and brain concentration of promazine, desmethylpromazine and promazine sulphoxide were determined using the HPLC method devised by us.

The effect of imipramine on lipid peroxidation in the rat cerebral cortex.

The effect of imipramine (IMI) on lipid peroxidation in the rat cerebral cortex was investigated in ex vivo and in vitro study. It was found that IMI when given to rats chronically (14 x 10 mg/kg ip) but not acutely (10 mg/kg ip), inhibited lipid peroxidation in the cortical membranes of rat brain. When added in different concentrations (0.