A role for CYP in the drug–hormone crosstalk of the brain

Abstract

Importance of the field: Libido disorders, menstruation problems, perception and cognition deficiencies are potentially undesired, but clinically emerging, side effects after long-term therapy with antiepileptic drugs or chemotherapeutic agents. These disorders were shown to occur predominantly in patients who had taken drugs interacting with the CYP system of the brain, particularly in the hippocampus, the hypothalamus, the cerebellum or in the amygdala. CYPs present and active in these regions usually inactivate steroid hormones such as testosterone.

Areas covered in this review: The present review focuses on recent concepts of brain CYP function, gives an outlook on neuroactive drug use in therapy and self-medication, and highlights the endocrine side effects after drug therapy in neurological diseases and brain tumors.

What the reader will gain: The reader is introduced to a CYP mediated drug–hormone crosstalk as a possible mechanism to explain these side effects.

Take home message: The drug–hormone crosstalk may be of considerable importance in the assessment of neuroactive drugs and future drug design.

Keywords::

• androgen receptor
• brain
• CYP
• drug–hormone crosstalk
• drug metabolism
• endocrine signaling
• neuroactive drug
• steroid hormone
• steroid hormone receptor
• testosterone

Acknowledgements

The work in the present review was supported by grants of the Deutsche Forschungsgemeinschaft (DFG Me1544/1 and DFG Me1544/4), the Forschungskommission of the University Hospital Freiburg (MEY 55/01, MEY 322/04, MEY 375/05 and MEY 465/06) and the Swiss National Foundation. The authors thank B Volk, UA Meyer, R Knoth, CE Hagemeyer, G Pantazis, N Killer, M Brandt, R Schwab, C Bürck, A Heisswolf and A Basters.

Notes

This box summarizes key points contained in the article.