Pharmacodynamics Selective estrogen receptor modulator<unk>  is a selective estrogen receptor modulator (SERM) with estrogenic and antiestrogenic actions. In the first study to evaluate the pharmacology of<unk> , it showed 25% of the affinity of estradiol for the estrogen receptor (ER) while afimoxifene had 35% of the affinity of estradiol for the ER. The antiestrogenic actions of<unk>  and afimoxifene in this study were very similar. In another study, the affinity of<unk>  for the ERα was 12.1% and its affinity for the ERβ was 4.75% relative to estradiol. For comparison, afimoxifene had relative binding affinities for the ERα and ERβ of 19.0% and 21.5% compared to estradiol, respectively. In yet another investigation, both<unk>  and afimoxifene had 181% of the affinity of estradiol for the ER whereas tamoxifen had 2.8% and N-desmethyltamoxifen had 2.4%. Protein kinase C inhibition The exact mechanism by which<unk>  exerts its therapeutic effects has not been established in bipolar I disorder. However, the efficacy of<unk>  could be mediated through protein kinase C (PKC). The PKC represents a family of enzymes highly enriched in the brain, where it plays a major role in regulating both pre-and post-synaptic aspects of neurotransmission. Excessive activation of PKC results in symptoms related to bipolar disorder. The PKC signaling pathway is a target for the actions of two structurally dissimilar antimanic agents – lithium and valproate.<unk>  exhibits 4-fold higher potency in inhibiting PKC activity compared to tamoxifen in preclinical studies and is not dependent on the isozyme cytochrome P450 2D6 (CYP2D6) for action on the target tissues. Pharmacokinetics Orally administered<unk>  is rapidly absorbed and systemically available. The time to peak (Tmax) is between 4.5 and 6 hours after oral administration. It is not metabolized by cytochrome P450 enzymes. The half-life (t½) life of<unk>  is 52.1 to 58.1 hours.
Endoxifen
Tamoxifen
Anastrozole
Salvestrol
N-Desmethyltamoxifen
Norendoxifen
Bazedoxifene
N,N-Didesmethyltamoxifen