Seltorexant, also known by its developmental code names MIN-202 and JNJ-42847922, is an

orexin antagonist An orexin receptor antagonist, or orexin antagonist, is a drug that inhibits the effect of orexin by acting as a receptor antagonist of one or both of the orexin receptors, Hypocretin (orexin) receptor 1, OX1 and Hypocretin (orexin) receptor 2, OX2. ...

medication which is under development for the treatment of depression and insomnia. It is a selective

antagonist An antagonist is a character in a story who is presented as the chief foe of the protagonist. Etymology The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, riv ...

of the orexin OX₂ receptor (2-SORA). The medication is taken by mouth. As of February 2022, seltorexant is in

phase 3 Phase 3, Phase III or Phase Three may refer to: Media * Marvel Cinematic Universe: Phase Three, eleven American superhero films from 2016–2019 * '' Phase 3: Thrones and Dominions'', a 1995 album by Earth * ''Phase III'' (album), a 1972 album ...

clinical trials for treatment of major depressive disorder (MDD) and

phase 2 Michael Lawrence Marrow (August 2, 1955 – December 12, 2019), known as PHASE 2 and Lonny Wood, was an American aerosol paint artist based in New York City. Mostly active in the 1970s, Phase 2 is generally credited with originating the "bubble l ...

trials for treatment of insomnia. It was also under investigation for the treatment of sleep apnea, but no recent development has been reported for this indication. Seltorexant is under development by Minerva Neurosciences and

Johnson & Johnson Johnson & Johnson (J&J) is an American multinational corporation founded in 1886 that develops medical devices, pharmaceuticals, and consumer packaged goods. Its common stock is a component of the Dow Jones Industrial Average and the company i ...

's Janssen Pharmaceuticals. Seltorexant is being explored at doses of 5 to 80mg. In the early clinical trials conducted so far, seltorexant has been found to improve depression scores on the Hamilton Depression Rating Scale in people with MDD and to improve sleep onset, total sleep time, time awake after sleep onset, and sleep efficiency in people with MDD and/or insomnia. Seltorexant is reported to be

safe A safe (also called a strongbox or coffer) is a secure lockable box used for securing valuable objects against theft or fire. A safe is usually a hollow cuboid or cylinder, with one face being removable or hinged to form a door. The body and ...

and well-tolerated. Side effects of seltorexant observed in clinical trials so far have included somnolence,

fatigue Fatigue describes a state of tiredness that does not resolve with rest or sleep. In general usage, fatigue is synonymous with extreme tiredness or exhaustion that normally follows prolonged physical or mental activity. When it does not resolve ...

, dizziness,

headache Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a result ...

, abdominal discomfort, and

nightmare A nightmare, also known as a bad dream, Retrieved 11 July 2016. is an unpleasant dream that can cause a strong emotional response from the mind, typically fear but also despair, anxiety or great sadness. The dream may contain situations of d ...

s. Seltorexant shows over 100-fold greater

binding affinity In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. The etymology stems from ''ligare'', which means 'to bind'. In protein-ligand binding, the ligand is usually a mol ...

for the OX₂ receptor over the OX₁ receptor. This is in contrast to other orexin receptor antagonists like

suvorexant Suvorexant, sold under the brand name Belsomra, is an orexin antagonist medication which is used in the treatment of insomnia. It is indicated specifically for the treatment of insomnia characterized by difficulties with sleep onset and/or mainte ...

, lemborexant, and

daridorexant Daridorexant, sold under the brand name Quviviq, is an orexin antagonist medication which is used for the treatment of insomnia. Daridorexant is taken by mouth. Side effects of daridorexant include headache, somnolence, and fatigue. The med ...

, which are all

dual orexin receptor antagonist An orexin receptor antagonist, or orexin antagonist, is a drug that inhibits the effect of orexin by acting as a receptor antagonist of one or both of the orexin receptors, OX1 and OX2. Medical applications include treatment of sleep disorders su ...

s (DORAs). Seltorexant has fast

absorption Absorption may refer to: Chemistry and biology * Absorption (biology), digestion **Absorption (small intestine) *Absorption (chemistry), diffusion of particles of gas or liquid into liquid or solid materials *Absorption (skin), a route by which ...

with a time to peak levels of 0.3 to 1.5hours and has a relatively short

duration Duration may refer to: * The amount of time elapsed between two events * Duration (music) – an amount of time or a particular time interval, often cited as one of the fundamental aspects of music * Duration (philosophy) – a theory of time and ...

with an elimination half-life of only 2 to 3hours. No residual effects of the medication were observed 4hours after daytime administration. The

pharmacokinetics Pharmacokinetics (from Ancient Greek ''pharmakon'' "drug" and ''kinetikos'' "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to determining the fate of substances administered ...

of seltorexant are considered to be ideal for

sleep induction Sleep induction is the deliberate effort to bring on sleep by various techniques or medicinal means, is practiced to lengthen periods of sleep, increase the effectiveness of sleep, and to reduce or prevent insomnia. Darkness and quiet Dim or dark ...

. Seltorexant is

metabolized Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...

by the

cytochrome P450 Cytochromes P450 (CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are ...

enzyme

CYP3A4 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine. It oxidizes small foreign organic molecules (xenobiotics), such as toxins or drugs, so that they can be removed from t ...

. It is a

small-molecule Within the fields of molecular biology and pharmacology, a small molecule or micromolecule is a low molecular weight (≤ 1000 daltons) organic compound that may regulate a biological process, with a size on the order of 1 nm. Many drugs ar ...

compound and is structurally related to other clinically used orexin receptor antagonists.

References

External links

Seltorexant — AdisInsight
{{Orexin receptor modulators Aminopyrimidines Antidepressants Experimental drugs Fluoroarenes Hypnotics Ketones Orexin antagonists Pyrroles Triazoles

See also

References

External links