Trifarotene is a novel first-in-class fourth-generation topical retinoid. It is a potent and selective RAR gamma-agonist. In multiple mouse models, trifarotene exhibited superior comedolytic, anti-inflammatory and depigmenting activity compared with other topical retinoids. In this 52-week study, trifarotene was safe, well-tolerated and effective in moderate facial and truncal acne. Trifarotene is in phase II clinical trial for the treatment of ichthyosis.

Siponimod (BAF312) is a dual agonist at the sphingosine-1 phosphate receptors, S1PR1 and S1PR5. The S1P receptor is commonly found on the surface of specific cells residing in the central nervous system (CNS), that are responsible for causing CNS damage that drives loss of function in secondary progressive multiple sclerosis (SPMS). Siponimod (BAF312) enters the brain and by binding to these specific receptors, may prevent the activation of these harmful cells, helping to reduce the loss of physical and cognitive function associated with SPMS.

Pitolisant (INN) or tiprolisant (USAN) is a histamine receptor inverse agonist/antagonist selective for the H3 subtype. It has stimulant and nootropic effects in animal studies and may have several medical applications, having been researched for the treatment of narcolepsy, for which it has been granted orphan drug status in the EU and US. It is currently in clinical trials for schizophrenia and Parkinson’s disease. Pitolisant hydrochloride was approved by European Medicine Agency (EMA) on Mar 31, 2016. It was developed and marketed as Wakix® by Bioprojet in EU. Wakix® is available as the tablet for oral use, containing 4.5 mg and 18 mg of Pitolisant hydrochloride. The initial dose of 9 mg (two 4.5 mg, tablets) per day, and it should be used at the lowest effective dose, depending on individual patient response and tolerance, according to an up-titration scheme, without exceeding the dose of 36 mg/day. Pitolisant was the first clinically used H3 receptor inverse agonist.

Cenobamate (also known as YKP3089) is a small molecule sodium channel blocker in development for the treatment of partial-onset seizures in adult patients. In mice and rats, Cenobamate displayed an anticonvulsant activity in the maximal electroshock test and prevented seizures induced by chemical convulsants such as pentylenetetrazol and picrotoxin. In addition, Cenobamate was reported to be effective in two models of focal seizure, the hippocampal kindled rat and the mouse 6 Hz psychomotor seizure models. Two completed adequate and well-controlled clinical studies demonstrated a significant reduction in focal seizures with Cenobamate in patients with epilepsy, and a long-term open-label phase 3 safety clinical trial is currently ongoing. Cenobamate is considered a new generation antiepileptic therapy and clinical trials have shown that it may be more effective and safer than existing drugs. If licensed, Cenobamate will offer a new adjunctive treatment option for patients with partial focal epilepsy.

Afamelanotide (SCENESSE) is a synthetic α-melanocyte stimulating hormone analog and first-in-class melanocortin-1 receptor agonist that is approved in the EU for the prevention of phototoxicity in adults with erythropoietic protoporphyria. Afamelanotide differs from endogenous α-melanocyte stimulating hormone at the fourth and seventh amino acid residues, increasing its resistance to immediate degradation and increasing its binding time to melanocortin-1 receptor. Afamelanotide is mimic the pharmacological activity of α-melanocyte stimulating hormone by binding to the melanocortin-1 receptor on melanocytes and activating the synthesis of eumelanin. Eumelanin provides photoprotection through mechanisms including, but not limited to, the absorption and scattering of visible and UV light and antioxidant activity. Afamelanotide increases eumelanin density in healthy volunteers and patients with erythropoietic protoporphyria. In healthy, fair-skinned volunteers, a significant increase in melanin density and skin darkening in both sun-exposed and non-sun-exposed sites was seen with subcutaneous injections of afamelanotide. The most common afamelanotide adverse events included headache and nausea. Common adverse effects include back pain, upper respiratory tract infections, decreased appetite, migraine, and dizziness.

Fluorodopa F-18 is the amino acid analog fluorodopa (FDOPA) labeled with fluorine F 18, a positron-emitting isotope. It is diagnostic PET agent, which has been used for decades in imaging the loss of dopaminergic neurons in Parkinson's disease, and more recently to detect, stage and restage neuroendocrine tumours and to search for recurrence of viable glioma tissue. Fluorodopa F-18 is able to cross the blood-brain barrier and is taken up by brain tumor cells. As uptake is higher in tumor cells, tumors may then be imaged using positron emission tomography (PET). Assessing tumor uptake of FDOPA may be beneficial for diagnosis, localization and in determining further treatment. The clinical usefulness of Fluorodopa F-18 has been evaluated and recognised in France and subsequently in several EU countries. Fluorodopa F-18 was registered in France in 2006. 6-fluoro-(18F)-L-3,4-dihydroxyphenylalanine (FDOPA) is a large, neutral amino acid that is transported into presynaptic neurons, where it is converted by the enzyme aromatic aminoacid decarboxylase [AAAD]) into fluorodopamine-(18F), which subsequently enters cathecholamine-storage vesicles. 6-fluoro(18F)-L-dopa crosses the blood-brain barrier; therefore, when injected into the blood stream, it reaches the dopaminergic cells in the brain and is used by the brain as a precursor for dopamine. This makes it possible to monitor intracerebral synthesis and uptake of dopamine by means of the positron-emitting 6-fluoro(18F)-L-3,4-dihydroxyphenylalanine (FDOPA), in conjunction with externally-placed devices suited for detection of annihilation photons, which progressively led to the most recent positron emission tomography (PET) units. Iasodopa, the commercial preparation of FDOPA that obtained a marketing authorisation in France in November 2006 (which is currently recognised by several other EU countries), is a solution for injection. The activity available at time of administration ranges from 0.1 GBq to 0.8 GBq per vial. The half-life of the radionuclide is 109.8 min with emission of positron radiation (Emax: 0.633 MeV) followed by photon annihilation radiations of 0.511 MeV.

Lusutrombopag (trade name Mulpleta) is an orally bioavailable, small molecule thrombopoietin (TPO) receptor agonist being developed by Shionogi for chronic liver disease (CLD) patients with thrombocytopenia prior to elective invasive surgery. Lusutrombopag acts selectively on the human TPO receptor and activates signal transduction pathways that promote the proliferation and differentiation of bone marrow cells into megakaryocytes, thereby increasing platelet levels. In September 2015, Lusutrombopag received its first global approval in Japan for the improvement of CLD-associated thrombocytopenia in patients scheduled to undergo elective invasive procedures. Oral Lusutrombopag is rapidly absorbed, with a median time to maximum serum concentration (Tmax) of 3.8–4.0 h in healthy subjects administered single doses of oral Lusutrombopag 1, 2 or 4 mg, and 6 h in CLD patients with thrombocytopenia administered oral Lusutrombopag 3 mg once daily for 7 days. The major metabolic pathway for Lusutrombopag appears to be omega- and beta-oxidation. Lusutrombopag is a substrate of breast cancer resistance protein and P-glycoprotein, according to in vitro data.

Lofexidine is newly FDA approved in the United States under the brand name LUCEMYRA for the treatment of opioid withdrawal symptoms in adults. Lofexidine acts as an agonist to α2 adrenergic receptors. These receptors inhibit adenylyl cyclase activity, leading to the inhibition of the second messenger, cyclic adenosine monophosphate (cAMP). The inhibition of cAMP leads to potassium efflux through calcium-activated channels, blocking calcium ions from entering the nerve terminal, resulting in suppression of neural firing, inhibition of norepinephrine release. Lofexidine replaces the opioid-driven inhibition of cAMP production and moderating the symptoms of opioid withdrawal.

Tafenoquine is anti-malaria drug originated in Walter reed army institute of research and developed by GSK and 60 Degrees Pharmaceuticals. In 2018 United States Food and Drug Administration (FDA) approved single dose tafenoquine for the radical cure (prevention of relapse) of Plasmodium vivax malaria. Tafenoquine, an 8-aminoquinoline antimalarial, is active against all the stages of Plasmodium species that include the hypnozoite (dormant stage) in the liver. Studies in vitro with the erythrocytic forms of Plasmodium falciparum suggest that tafenoquine may exert its effect by inhibiting hematin polymerization and inducing apoptotic like death of the parasite. In addition to its effect on the parasite, tafenoquine causes red blood cell shrinkage in vitro. Tafenoquine is active against pre-erythrocytic (liver) and erythrocytic (asexual) forms as well as gametocytes of Plasmodium species that include P. falciparum and P. vivax. The activity of tafenoquine against the pre-erythrocytic liver stages of the parasite, prevents the development of the erythrocytic forms of the parasite.

Revefenacin (trade name Yupelri is a long-acting muscarinic antagonist developed by Mylan Ireland ltd for the treatment of chronic obstructive pulmonary disease (COPD). It has similar affinity to the subtypes of muscarinic receptors M1 to M5. In the airways, it exhibits pharmacological effects through inhibition of M3 receptor at the smooth muscle leading to bronchodilation. The competitive and reversible nature of antagonism was shown with human and animal origin receptors and isolated organ preparations. In preclinical in vitro as well as in vivo models, prevention of methacholine- and acetylcholine-induced bronchoconstrictive effects was dose-dependent and lasted longer than 24 hours.