N-Desmethylenzalutamide

Desmethylenzalutamide

N-Desmethylenzalutamide is a nonsteroidal antiandrogen (NSAA) that is a major active metabolite of the drug enzalutamide (brand name Xtandi). It is formed in the body through the process of demethylation of enzalutamide. N-Desmethylenzalutamide retains significant antiandrogenic activity and contributes to the overall therapeutic effects of enzalutamide in the treatment of prostate cancer.

Pharmacology

N-Desmethylenzalutamide functions by binding to the androgen receptor (AR) and inhibiting its activation by androgens such as testosterone and dihydrotestosterone (DHT). This inhibition prevents the androgen receptor from translocating to the cell nucleus and modulating the expression of androgen-responsive genes, which are involved in the growth and survival of prostate cancer cells.

Metabolism

Enzalutamide is metabolized in the liver primarily by the cytochrome P450 enzyme CYP2C8, with minor contributions from CYP3A4. The demethylation of enzalutamide to form N-Desmethylenzalutamide is a key step in its metabolic pathway. N-Desmethylenzalutamide itself is further metabolized to other inactive compounds before being excreted from the body.

Clinical Significance

The presence of N-Desmethylenzalutamide in the bloodstream of patients taking enzalutamide is an important factor in the drug's efficacy. The metabolite's antiandrogenic activity helps to sustain the suppression of androgen receptor signaling, which is crucial for the treatment of castration-resistant prostate cancer (CRPC).

Side Effects

The side effects of N-Desmethylenzalutamide are generally similar to those of enzalutamide, as both compounds act on the same target. Common side effects include fatigue, hot flashes, and hypertension. More serious side effects can include seizures and other neurological effects, which are thought to be related to the drug's ability to cross the blood-brain barrier.

See Also

• Enzalutamide
• Androgen receptor
• Prostate cancer
• Nonsteroidal antiandrogen

References

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