Ulotaront (;https://cdn.who.int/media/docs/default-source/international-nonproprietary-names-(inn)/pl124.pdf?sfvrsn=6437f035_10&download=true developmental codes SEP-363856, SEP-856) is an investigational

antipsychotic Antipsychotics, also known as neuroleptics, are a class of psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but also in a range of ...

that is undergoing

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, diet ...

s for the treatment of

schizophrenia Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social wit ...

and

Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...

psychosis Psychosis is a condition of the mind that results in difficulties determining what is real and what is not real. Symptoms may include delusions and hallucinations, among other features. Additional symptoms are incoherent speech and behavior ...

. The medication was discovered in collaboration between PsychoGenics Inc. and Sunovion Pharmaceuticals using PsychoGenics' behavior and AI-based phenotypic drug discovery platform, SmartCube. Ulotaront is in Phase III of clinical development. Research has shown that ulotaront results in a greater reduction from baseline in the PANSS total score than

placebo A placebo ( ) is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets (like sugar pills), inert injections (like saline), sham surgery, and other procedures. In general, placebos can af ...

. Treatment with ulotaront, as compared with

, was also associated with an improvement in

sleep Sleep is a sedentary state of mind and body. It is characterized by altered consciousness, relatively inhibited sensory activity, reduced muscle activity and reduced interactions with surroundings. It is distinguished from wakefulness by a de ...

quality. Ulotaront was awarded a

Breakthrough Therapy designation Breakthrough therapy is a United States Food and Drug Administration designation that expedites drug development that was created by Congress under Section 902 of the 9 July 2012 Food and Drug Administration Safety and Innovation Act. The FDA's "br ...

due to its increased efficacy and greatly reduced side effects compared to current treatments.

Adverse effects

The

adverse effect An adverse effect is an undesired harmful effect resulting from a medication or other intervention, such as surgery. An adverse effect may be termed a " side effect", when judged to be secondary to a main or therapeutic effect. The term compl ...

profile of ulotaront differs from that of other antipsychotics because its

mechanism of action In pharmacology, the term mechanism of action (MOA) refers to the specific biochemical interaction through which a drug substance produces its pharmacological effect. A mechanism of action usually includes mention of the specific molecular targ ...

does not involve antagonism of

dopamine receptor Dopamine receptors are a class of G protein-coupled receptors that are prominent in the vertebrate central nervous system (CNS). Dopamine receptors activate different effectors through not only G-protein coupling, but also signaling through diffe ...

s in the

brain A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a ve ...

, which is responsible for the drug-induced

movement disorder Movement disorder refers to any clinical syndrome with either an excess of movement or a paucity of voluntary and involuntary movements, unrelated to weakness or spasticity. Movement disorders are synonymous with basal ganglia or extrapyramidal ...

s (like

akathisia Akathisia is a movement disorder characterized by a subjective feeling of inner restlessness accompanied by mental distress and an inability to sit still. Usually, the legs are most prominently affected. Those affected may fidget, rock back a ...

) that may occur with those agents. Some adverse events reported in preliminary clinical trials are somnolence, agitation, nausea, diarrhea, and

dyspepsia Indigestion, also known as dyspepsia or upset stomach, is a condition of impaired digestion. Symptoms may include upper abdominal fullness, heartburn, nausea, belching, or upper abdominal pain. People may also experience feeling full earlier ...

Pharmacology

Mechanism of action

The mechanism of action of ulotaront in the treatment of schizophrenia is unclear. However, it is thought to be an agonist at the

trace amine-associated receptor 1 Trace amine-associated receptor 1 (TAAR1) is a trace amine-associated receptor (TAAR) protein that in humans is encoded by the ''TAAR1'' gene. TAAR1 is an intracellular amine-activated and G protein-coupled receptor (GPCR) that is primarily ex ...

(TAAR1) and serotonin 5-HT_1A receptors. This mechanism of action is unique among available antipsychotics, which generally antagonize dopamine receptors (especially dopamine D₂ receptor).

Pharmacokinetics

The precise pharmacokinetic profile of ulotaront has not been reported, though the developer has suggested that the pharmacokinetic data supports once daily dosing.

Research

As of 2018, Sunovion, the maker of another antipsychotic called

lurasidone Lurasidone, sold under the trade name Latuda among others, is an antipsychotic medication used to treat schizophrenia and bipolar disorder. It is taken by mouth. Common side effects include sleepiness, movement disorders, nausea, and diarrhea. ...

(Latuda), is conducting clinical trials on ulotaront in partnership with the preclinical research company PsychoGenics. The U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

has granted ulotaront the

breakthrough therapy Breakthrough therapy is a United States Food and Drug Administration designation that expedites drug development that was created by Congress under Section 902 of the 9 July 2012 Food and Drug Administration Safety and Innovation Act. The FDA's "br ...

designation. In addition to schizophrenia, ulotaront is also being studied for the treatment of psychosis associated with

Interesting facts

Ulotaront and ralmitaront are TAAR1 agonists which have reached clinical trials. The result of adding the first two letters of names "ralmitaront" and "ulotaront" to each other forms the name "Raul". Raul Gainetdinov is one of the pioneers in Trace-Amine Associated Receptors' research.

References

External links

Ulotaront - AdisInsight
{{TAAR ligands 5-HT1A agonists Amines Antipsychotics Experimental drugs TAAR1 agonists Thiophenes