The influence of long-term treatment with psychotropic drugs on cytochrome P450: the involvement of different mechanisms

Abstract

This paper emphasises that besides the direct action of psychotropic drugs on cytochrome P450 (CYP) (i.e., the binding of the parent drug to the enzyme) indirect mechanisms of CYP–psychotropic interactions, namely the formation of CYP-reactive metabolite complexes and their influence on enzyme regulation, are also very important. The described interactions that are time-, drug- and CYP isoform-dependent may overlap during long-term treatment. The final result of the overlapping depends on the dosage and time interval after the last administration of a drug, which determines the concentration of the parent drug and its metabolites in the environment of the enzyme. These interactions may occur not only in the liver, but also in the brain, and may change the activity of CYP towards the metabolism of drugs, sex steroids, neurosteroids and amine neurotransmitters. The role of the CNS in the regulation of CYP by psychotropics and the significance of CYP–psychotropic interactions for pharmacological and clinical profiling of these drugs is discussed. In addition, different experimental approaches for studying CNS-acting drugs are compared.

Keywords::

• antidepressants
• binding
• brain
• CNS
• CYP isoforms
• cytochrome P450
• drug metabolism
• enzyme regulation
• interaction
• liver
• neuroleptics
• psychotropic drugs
• reactive metabolites