Difelikefalin (Korsuva™) is a synthetic peptide agonist of the kappa opioid receptor being developed by Cara Therapeutics for the treatment of pruritus. In August 2021, intravenous difelikefalin was approved in the USA for the treatment of moderate-to-severe pruritus associated with chronic kidney disease (CKD) in adults undergoing haemodialysis. Difelikefalin selectively acts on kappa opioid receptors in peripheral tissues, which contribute to pruritis and nociception. The activation of opioid receptors in peripheral neurons and keratinocytes reduces afferent (sensory) impulses towards the central nervous system, decreasing pain signals. Activating kappa opioid receptors on immune cells, including monocytes and T lymphocytes, decreases the release of pro-inflammatory chemicals such as prostaglandins.

Artenimol (dihydroartemisinin) is a derivate of antimalarial compound artemisinin. Artenimol (dihydroartemisinin) is able to reach high concentrations within the parasitized erythrocytes. Its endoperoxide bridge is thought to be essential for its antimalarial activity, causing free-radical damage to parasite membrane systems including: • Inhibition of falciparum sarcoplasmic-endoplasmic reticulum calcium ATPase, • Interference with mitochondrial electron transport • Interference with parasite transport proteins • Disruption of parasite mitochondrial function. Dihydroartemisinin in combination with piperaquine tetraphosphate (Eurartesim, EMA-approved in 2011) is indicated for the treatment of uncomplicated Plasmodium falciparum malaria. The formulation meets WHO recommendations, which advise combination treatment for Plasmodium falciparum malaria to reduce the risk of resistance development, with artemisinin-based preparations regarded as the ‘policy standard’. However, experimental testing demonstrates that, due to its intrinsic chemical instability, dihydroartemisinin is not suitable to be used in pharmaceutical formulations. In addition, data show that the currently available dihydroartemisinin preparations fail to meet the internationally accepted stability requirements.

(+)-alpha-Dihydrotetrabenazine (HTBZ) is an active component of tetrabenazine. Tetrabenazine is a mixture of closely-related compounds (isomers) and is readily metabolized in the human body to HTBZ and related isomers. Tetrabenazine is a drug for the symptomatic treatment of hyperkinetic movement disorder and is marketed under the trade names Nitoman in Canada and Xenazine in New Zealand and some parts of Europe, and is also available in the USA as an orphan drug. (+)-alpha-Dihydrotetrabenazine and related benzo[a]quinolizines have been labeled with tritium and carbon-11 radioisotopes and used for in vitro and in vivo studies of the VMAT2 in animal and human brain. Adeptio Pharmaceuticals is developing alpha-dihydrotetrabenazine (HTBZ) for the treatment of neurological disorders. It acts by inhibiting vesicular monoamine transporter 2 (VMAT2), thereby blocking the transport of dopamine into axon terminals or into storage vesicles.

Dehydroepiandrosterone (INTRAROSA™, prasterone) is a major C19 steroid produced from cholesterol by the adrenal cortex. It is also produced in small quantities in the testis and the ovary. Dehydroepiandrosterone (INTRAROSA, prasterone) is structurally similar to, and is a precursor of, androstenedione, testosterone, estradiol, estrone and estrogen. It indicated for the treatment of moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause. The mechanism of action of dehydroepiandrosterone (INTRAROSA, prasterone) in postmenopausal women with vulvar and vaginal atrophy is not fully established.

Eslicarbazepine acetate is a third generation antiepileptic drug indicated for the treatment of partial-onset seizures. Structurally, it belongs to the dibenzazepine family and is closely related to carbamazepine and oxcarbazepine. Eslicarbazepine acetate was developed by scientists in Portugal. Its main mechanism of action is by blocking the voltage-gated sodium channel. Eslicarbazepine acetate is a pro-drug that is rapidly metabolized almost exclusively into eslicarbazepine (S-licarbazepine), the biologically active drug. It has a favorable pharmacokinetic and drug-drug interaction profile. However, it may induce the metabolism of oral contraceptives and should be used with caution in females of child-bearing age.

Bazedoxifene acetate (WAY-140424; TSE-424) is an oral, nonsteroidal, indole-based selective estrogen-receptor modulator developed by Ligand Pharmaceuticals in collaboration with Wyeth Pharmaceuticals (NJ, USA) (now Pfizer) . It was developed using raloxifene as a template with the benzothiophene core substituted by an indole ring in order to obtain favorable effects on the skeleton and lipid metabolism with the additional improvement of a neutral effect on hot flushes and without stimulating the uterus or the breast. The drug is approved as a monotherapy for the prevention and treatment of osteoporosis and in combination with conjugated estrogens for the treatment of menopausal symptoms and prevention of osteoporosis. Bazedoxifene binds to both ERalpha and ERbeta with high affinity. Bazedoxifene acts as both a receptor agonist and/or antagonist, depending upon the cell and tissue type and target genes. Bazedoxifene decreases bone resorption and reduces biochemical markers of bone turnover to the premenopausal range. These effects on bone remodeling lead to an increase in bone mineral density (BMD), which in turn contributes to a reduction in the risk of fractures. Bazedoxifene functions primarily as an estrogen-receptor antagonist in uterine and breast tissues.

Crizotinib (trade name Xalkori, Pfizer, Inc.) is an anti cancer drug approved for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test. Crizotinib is an inhibitor of receptor tyrosine kinases including ALK, Hepatocyte Growth Factor Receptor (HGFR, c-Met), ROS1 (c-ros), and Recepteur d’Origine Nantais (RON). Common adverse reactions in clinical trials with crizotinib, occurring at an incidence of 25% or higher, included visual disorders, nausea, diarrhea, vomiting, constipation, edema, elevated transaminases, and fatigue. Crizotinib is currently under investigational study for use in treatment of Uveal Melanoma.

Icatibant (trade name Firazyr) is a synthetic peptidomimetic drug consisting of ten amino acids, and acts as an effective and specific antagonist of bradykinin B2 receptors. It has been approved in the EU for use in hereditary angioedema, and is under investigation for a number of other conditions in which bradykinin is thought to play a significant role. Icatibant currently has orphan drug status in the United States and FDA approved on August 25, 2011. Icatibant inhibits bradykinin from binding the B2 receptor and thereby treats the clinical symptoms of an acute, episodic attack of HAE.

Abiraterone acetate (trade name Zytiga) is a prodrug to the abiraterone, steroidal compound with antiandrogen activity and a 17 α-hydroxylase/C17,20-lyase (CYP17) inhibitor. It is indicated in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer. Abiraterone acetate is converted in vivo to abiraterone which inhibits CYP17, enzyme expressed in testicular, adrenal, and prostatic tumor tissues and required for androgen biosynthesis. Administration of this agent may suppress testosterone production by both the testes and the adrenals to castrate-range levels. Androgen sensitive prostatic carcinoma responds to treatment that decreases androgen levels. Androgen deprivation therapies, such as treatment with GnRH agonists or orchiectomy, decrease androgen production in the testes but do not affect androgen production by the adrenals or in the tumor.

Ulipristal acetate (also known as CDB-2914 and PGL4001 and trade name Ella in the U.S) is a novel oral emergency contraceptive designed and developed by HRA Pharma. It is a selective progesterone receptor modulator, which reversibly blocks the progesterone receptors in target tissues it was approved in May 2009 by the European Commission and in August 2010 by the FDA as safe and effective in preventing unintended pregnancy for up to 120 hours – or five days – post- unprotected intercourse or contraceptive failure. Ella is not intended for routine use as a contraceptive. When taken immediately before ovulation is to occur, ella postpones follicular rupture. The likely primary mechanism of action of ulipristal acetate for emergency contraception is therefore inhibition or delay of ovulation; however, alterations to the endometrium that may affect implantation may also contribute to efficacy. The most common side effects are: headache, nausea, stomach (abdominal) pain, menstrual pain. Some women taking ella may have their next period earlier or later than expected. If your period is more than a week late, you should get a pregnancy test.