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.

Lemborexant is a dual orexin receptor antagonist, which inhibits orexin by binding competitively to two subtypes of orexin receptors. During normal periods of sleep, orexin system activity is suppressed, suggesting it is possible to purposefully facilitate the initiation and maintenance of sleep by interfering with orexin neurotransmission with lemborexant. Extensive in vitro and non-clinical testing of lemborexant supported the supposition that lemborexant has a low risk of QT prolongation at therapeutic and supratherapeutic exposures in humans. A Phase III study of lemborexant in insomnia is underway, and in addition, Eisai has announced the initiation of Phase II clinical studies of lemborexant in patients with irregular sleep-wake rhythm disorder.

LASMIDITAN is a serotonin (5-HT) receptor agonist without vasoconstrictor activity, which selectively binds to the 5-HT(1F) receptor subtype. It is under development for the treatment of migraine.

Bremelanotide (formerly PT-141) was developed for the treatment of female sexual dysfunction, hemorrhagic shock, and reperfusion injury. Bremelanotide, a synthetic peptide analog of α-melanocyte-stimulating hormone (α-MSH) is an agonist at melanocortin receptors including the MC3R and MC4R, which are expressed primarily in the central nervous system. Bremelanotide originally was tested for intranasal administration in treating female sexual dysfunction but this application was temporarily discontinued in 2008 after concerns were raised over adverse side effects of increased blood pressure. It appears that development for hemorrhagic shock and reperfusion injury has been discontinued. Palatin Technologies licensed North American development and commercialization rights of bremelanotide to Amag in January 2017. In June 2018, the US Food and Drug Administration (FDA) accepted AMAG Pharmaceuticals’ new drug application for bremelanotide for treatment of hypoactive sexual desire disorder in premenopausal women. If approved, bremelanotide will be available as a self-administered, disposable subcutaneous auto-injector used in anticipation of a sexual encounter.

Triclabendazole, (brand name Avomec, Egaten, etc) is a member of the benzimidazole family of anthelmintics used to treat liver flukes, specifically fascioliasis and paragonimiasis. Triclabendazole used routinely since 1983 in veterinary practice for the treatment of fascioliasis. It was not used in humans until the 1989 epidemic of fascioliasis near the Caspian Sea when Iranian authorities approved the use of the veterinary formulation to treat the infection. Fasciolicidal not only against the adult worms present in the biliary ducts, but also against the immature larval stages of Fasciola migrating through the hepatic parenchyma. Triclabendazole is shown to penetrate into liver flukes by transtegumentary absorption followed by inhibition of the parasite's motility, probably related to the destruction of the microtubular structure, resulting in the death of the parasite; the immobilizing effect is paralleled by changes in the parasite's resting tegumental membrane potential, strongly inhibiting the release of proteolytic enzymes, a process that appears critical to the survival of the parasite. Side effects are generally few, but can include abdominal pain and headaches. Biliary colic may occur due to dying worms. While no harms have been found with use during pregnancy, triclabendazole has not been well studied in this population. Triclabendazole is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. It is not commercially available in the United States.

Pexidartinib (PLX3397) is a small-molecule receptor tyrosine kinase (RTK) inhibitor with potential antineoplastic activity. Pexidartinib binds to and inhibits phosphorylation of stem cell factor receptor (KIT), colony-stimulating factor-1 receptor (CSF1R) and FMS-like tyrosine kinase 3 (FLT3), which may result in the inhibition of tumor cell proliferation and down-modulation of macrophages, osteoclasts and mast cells involved in the osteolytic metastatic disease. FDA has granted Breakthrough Therapy Designation to pexidartinib (PLX3397) for the treatment of tenosynovial giant cell tumor (TGCT) where surgical removal of the tumor would be associated with potentially worsening functional limitation or severe morbidity. In addition to Breakthrough Therapy Designation, pexidartinib (PLX3397) has been granted Orphan Drug Designation by FDA for the treatment of pigmented villonodular synovitis (PVNS) and giant cell tumor of the tendon sheath (GCT-TS). It also has received Orphan Designation from the European Commission for the treatment of TGCT.

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.

Cannabidiol is the major nonpsychoactive ingredient in cannabis. Cannabidiol demonstrates a range of effects that may be therapeutically useful, including anti-seizure, antioxidant, neuroprotective, anti-inflammatory, analgesic, anti-tumor, anti-psychotic, and anti-anxiety properties. Exact mechanism of action of cannabidiol is not known, but may include effects on the orphan G-protein-coupled receptor GPR55; the transient receptor potential of vanilloid type-1 channel; the 5-HT1a receptor; and the α3 glycine receptors. GW Pharmaceuticals successfully developed the world’s first prescription medicine derived from the cannabis plant, Sativex® (buccal spray containing delta-9-tetrahydrocannabinol and cannabidiol) now approved in over 29 countries outside of the United States for the treatment of spasticity due to Multiple Sclerosis. GW Pharmaceuticals is developing Epidiolex® (a liquid formulation of pure plant-derived cannabidiol) for certain rare and severe early-onset, drug-resistant epilepsy syndromes.