Fate of drug-metabolizing enzymes in neurological diseases: Challenges and strategies

Over the last few decades, the limitation of knowledge and resistance of neuropsychiatric drugs has become a major unmet problem due to therapeutic failure. In order to maintain local cerebral homeostasis, drug-metabolizing enzymes (DME) play a crucial role in the metabolism of neuropsychiatric drugs, xenobiotics, and various other therapeutic drugs. There is evidence of particular interest where it is reported that CYP2D6 polymorphism can affect the basic brain function. Altered pharmacokinetics aspects of drugs due to genetic variation and DME activity expressed in brain cells can not only adversely affect the treatment regime but can also lead to central toxicity and cost maximization. DME polymorphisms within cerebral tissue contribute enough to treatment failure and personality and can make individuals vulnerable to the onset and progression of various neurological diseases. Knowing the unknown about DME polymorphisms and its association with neuropsychiatric disorders will help in the possibility of delivering “personalized medicine” based on empirical evidence justifying pharmacogenetic dose adjustments. This chapter summarizes the evidence about drug-metabolizing enzymes, the challenges, and strategies of DME polymorphisms in brain function and its effects on various neuropsychological disorders.