Introduction
The active ingredient tamoxifen, which is usually used in salt form, i.e. as tamoxifen dihydrogen citrate, is a selective estrogen receptor modulator (SERM). In the past, the active ingredients of this group were also known as antiestrogens. Active ingredients of this group mediate their action via estrogen receptors that are present in various tissues, such as the pituitary gland (hypophysis), breast, uterus and bone.
In simple terms, tamoxifen causes a reduction in cell division in estrogen-dependent tissues; thus, on the one hand, tissue perishes and on the other hand, further growth of the tissue is prevented. Tamoxifen is normally administered as a film-coated tablet. The tablets contain either 10 mg, 20 mg, 30 mg or 40 mg tamoxifen.
The treating physician determines the dosage to be used. A daily dosage of 20 mg is usually sufficient. Tamoxifen is a prescription drug.
Tamoxifen is a prodrug, i.e. a low active pharmacological substance which is only converted into the active ingredient by a metabolism (metabolization) in the body. In the case of tamoxifen, an enzyme of the cytochrome P450 enzyme family is responsible for this. The enzyme is called CYP2D6 and converts tamoxifen into the active metabolite endoxifen.
It is known that the gene of the enzyme CYP2D6 may have a different structure in different individuals (gene polymorphism). Therefore, the activation step from tamoxifen to endoxifene may be different in different individuals. In so-called slow-onset tamoxifen metabolisers, the activation and thus also the effect of the drug is delayed, which is why these patients can benefit from an alternative therapy. In general, it is therefore recommended to determine the CYP2D6 genotype in order to rule out possible abnormalities of the gene before starting treatment.
Mode of action (pharmacodynamics)
As described above, tamoxifen is a selective estrogen receptor modulator (SERM) that acts by binding to estrogen receptors. The active metabolites 4-hydroxytamoxifen and endoxifen, which are formed from tamoxifen, have an even stronger binding to estrogen receptors. Tamoxifen can be described as a so-called partial agonist.
A partial agonist is a substance that binds to a receptor and thus partially mimics the action of the actual substance that binds to this receptor (for example the hormone estrogen in the case of the estrogen receptor). Compared to a full agonist, a partial agonist causes only an incomplete activation of the signaling cascade associated with the receptor. In that a partial agonist prevents the binding of the full agonist or displaces it from binding, the effect of the full agonist is partially inhibited by a partial agonist.
With regard to tamoxifen, this means that tamoxifen has an estrogenic active component on the one hand, but also an antiestrogenic active component on the other. The antiestrogenic component is produced by the displacement of estrogen from its receptor bond. Which component predominates depends on the tissue type.
In breast tissue, the estrogen receptor of the ER? type is predominantly found, where tamoxifen develops an antiestrogenic effect. This explains the antitumor effect of tamoxifen on breast cancer. The estrogenic effect of tamoxifen on the uterus explains the increased occurrence of benign and malignant changes in the uterus and endometrium.
