Tamoxifen

Category: pharmacological

Aliases: Nolvadex, ICI 46474

Pharmacological Mechanism

Triphenylethylene SERM. Tissue-selective ER agonism/antagonism: antagonist in breast (anti-proliferative, primary indication), partial agonist in bone (protective) + endometrium (hyperplasia / cancer risk) + liver (lipid + clotting-factor effects). Activity driven primarily by the CYP2D6-derived metabolite endoxifen (~100× ER affinity vs parent). In men: blocks hypothalamic ER-mediated negative feedback → raises LH/FSH → testicular testosterone — rationale for PCT after AAS cycles and off-label treatment of gynaecomastia.

Half-Life (t½)

PO: 96h

Dosing Guidelines

• PO: Typical 20 mg (Range: 10–40 mg)

Target Organ Systems

• nervous
• endocrine
• digestive
• reproductive
• musculoskeletal

Interactions

• Anastrozole (caution): Co-administration reduces anastrozole AUC ~27%. Sequential rather than combined.
• Paroxetine / strong CYP2D6 inhibitors (major): Blocks CYP2D6-mediated endoxifen formation — reduces efficacy. Choose non-inhibitor SSRI (venlafaxine, citalopram) in hot-flash management. [Zanger 2004]
• Warfarin (major): CYP2C9 inhibition + estrogenic hepatic effects raise INR — monitor closely. [Holbrook 2005]
• Clomiphene (caution): both SERMs with overlapping ER modulation — combination not standard; clomiphene's hypothalamic-axis effects may complicate breast cancer ER blockade

Pathways It Modulates

• Aromatase + androgen receptor (inhibitor) — ER (SERM, breast-antagonist)
• Estrogen receptor (ERα / ERβ / GPER) (inhibitor) — ERα tissue-specific (breast antag, uterus agon)

Chemical Identifiers

• PubChem CID: 2733526
• Formula: C26H29NO
• Molecular weight: 371.51 g/mol
• InChIKey: NKANXQFJJICGDU-QPLCGJKRSA-N
• SMILES: CC/C(=C(\C1=CC=CC=C1)/C2=CC=C(C=C2)OCCN(C)C)/C3=CC=CC=C3

References

• PMID 31008668
• PMID 14618296
• PMID 15911722
• PMID 36836506
• PMID 9048584