Brilaroxazine (developmental code names RP-5063 and RP-5000), also known as oxaripiprazole, is an investigational atypical antipsychotic which is under development by Reviva Pharmaceuticals for the treatment of schizophrenia and schizoaffective disorder. Reviva Pharmaceuticals also intends to investigate brilaroxazine for the treatment of bipolar disorder, major depressive disorder, psychosis/ agitation associated with

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, Parkinson's disease psychosis, attention deficit hyperactivity disorder (ADD/ADHD), and

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. As of August 2022, it is in phase III clinical trials for schizophrenia.

Pharmacology

Pharmacodynamics

Brilaroxazine is described as a so-called "dopamine-serotonin system stabilizer" due to its unique actions on the

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic compound, organic chemical of the catecholamine and phenethylamine families. Dopamine const ...

and

serotonin Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vas ...

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neuro ...

systems compared to other antipsychotics. Specifically, it acts as a partial agonist of the D₂, D₃, and D₄ receptors and of the 5-HT_1A and 5-HT_2A receptors, and as an

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 5-HT₆ and 5-HT₇ receptors. Brilaroxazine has high

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for the D_2S, D_2L, D₃, D_4.4, 5-HT_1A, 5-HT_2A, 5-HT₇, and H₁ receptors, and moderate affinity for the D₁, D₅, 5-HT₃, 5-HT₆ receptors, the serotonin transporter, and the α_1B-adrenergic receptor. It lacks significant affinity for the 5-HT_1B, 5-HT_2C, α₂-adrenergic, and muscarinic acetylcholine receptors, as well as for the norepinephrine and dopamine transporters.

Chemistry

Brilaroxazine is identical to aripiprazole in chemical structure except for the replacement of one of the carbon atoms in aripiprazole's

quinolinone Quinolone may refer to: * 2-Quinolone * 4-Quinolone 4-Quinolone is an organic compound derived from quinoline. It and 2-quinolone are the two most important parent (meaning simplified) quinolones. 4-Quinolone exists in equilibrium with a mino ...

ring system with an oxygen atom, resulting instead in a benzoxazinone ring system. The drug is also closely related structurally to

brexpiprazole Brexpiprazole, sold under the brand name Rexulti among others, is an atypical antipsychotic. It is a dopamine D2 receptor partial agonist and has been described as a "serotonin–dopamine activity modulator" (SDAM). The drug was approved by th ...

and cariprazine.

Recent Developments

In August, 2022, Reviva Pharmaceuticals, the manufacturer of brilaroxazine, announced successful enrollment of approximately one fifth of study participants for a phase III clinical trial of the drug. The study, which includes clinical sites in the United States, Europe and Asia, aims to assess the efficacy of this agent in the treatment of schizophrenia. An anticipated study completion date in March 2023 is anticipated.

References

External links