• contribution of brain cytochromes P450 to the local metabolism of monoaminergic neurotransmitters and psychoactive drugs;
• role of the central nervous system in the regulation of cytochrome P450 expression;
• interaction between psychotropic drugs and cytochrome P450 isoenzymes in the brain and liver;
• identification and quantitative contribution of liver cytochrome P450 isoenzymes to the metabolism of centrally active drugs;
• pharmacokinetic interactions within clinical combinations of psychotropics;
• mechanisms of pharmacokinetic interactions;
• pharmacokinetics and metabolism of psychotropic drugs after acute and chronic treatment;
• relationships between drug concentration in blood plasma and the brain: mechanisms of drug distribution.

Pharmacokinetics and drug metabolism:
- determination of the concentrations of psychotropic drugs and their metabolites in blood plasma, brain and peripheral tissues using HPLC (UV and fluorescence detection);
- drug metabolism in vitro: measurement of the rate of drug metabolism in liver microsomes in the absence or presence of cytochrome P450 specific inhibitors - kinetic study, calculation of K_m, V_max, CL and the inhibition constant K_i (HPLC);
- assessment of the ability of cDNA-expressed cytochrome P450 isoenzymes to catalyse metabolic reactions - calculation of kinetic parameters, K_m, V_max and CL (HPLC);
- distribution study: assessment of tissue drug uptake in vitro (HPLC, spectrofluorimetry or liquid scintillation counting).

Biochemistry:
- determination of the concentrations of monoaminergic neurotransmitters and their metabolites in the brain using HPLC (electrochemical detection);
- estimation of cytochrome P450 activity in brain and liver microsomes by isoenzyme-specific reactions (HPLC);
- assessment of the concentrations of cytochrome P450 specific substrates (testosterone, caffeine, ethylmorphine, bufuralol, warfarin) and their metabolites in brain and liver microsomes using HPLC (UV and fluorescence detection);
- evaluation of total cytochrome P450 and cytochrome b-5 concentrations in liver microsomes (double-beam spectrophotometry;
- assessment of the ability of liver/brain microsomes and cDNA-expressed cytochrome P450 isoenzymes to catalyse endogenous substrate metabolism - calculation of kinetic parameters, K_m, V_max, CL and K_i (HPLC);
- determination of the concentrations of cytochrome P450 isoenzyme proteins in brain and liver microsomes by electrophoresis and Western blot, followed by immunodetection and chemoluminescence measurement (Luminescent Image Analyzer LAS-100);
- determination of hormone and cytokine levels in blood plasma/serum (ELISA, Multiscan Spectrum UV microplate reader).

Others:
- stereotaxic implantation of cannula in brain structures (intracerebral injections).

The Department cooperates with:

the Institut National de la Santé et de la Rechere Medicale (INSERM), Montpellier (France)

- cytochrome P450 expression in steam cells and hepatocytes.

Engineers, Technicians, and Other Employees: