Lu AA41063

Lu AA41063, also known as Brexpiprazole, is an atypical antipsychotic medication developed by H. Lundbeck and Otsuka Pharmaceutical. It is primarily used in the treatment of schizophrenia and as an adjunctive therapy for major depressive disorder (MDD). Brexpiprazole was approved by the United States Food and Drug Administration (FDA) in July 2015 under the brand name Rexulti.

Pharmacology

Brexpiprazole is a serotonin-dopamine activity modulator (SDAM) that acts as a partial agonist at the 5-HT_1A and D₂ receptors, and as an antagonist at the 5-HT_2A receptor. It also has affinity for the α₁-adrenergic and H₁ receptors, which may contribute to its side effect profile.

Mechanism of Action

Brexpiprazole's mechanism of action is thought to involve modulation of the dopaminergic and serotonergic systems in the brain. By acting as a partial agonist at the D₂ receptor, it stabilizes dopamine activity, which is believed to help alleviate symptoms of schizophrenia and depression. Its antagonistic action at the 5-HT_2A receptor may also contribute to its antipsychotic effects.

Clinical Uses

Brexpiprazole is indicated for the treatment of:

• Schizophrenia
• Adjunctive treatment of major depressive disorder (MDD)

Efficacy

Clinical trials have demonstrated that brexpiprazole is effective in reducing the symptoms of schizophrenia and improving depressive symptoms when used as an adjunctive treatment in MDD. It is generally well-tolerated, with a side effect profile similar to other atypical antipsychotics.

Side Effects

Common side effects of brexpiprazole include weight gain, akathisia, and somnolence. Less common but serious side effects may include tardive dyskinesia, neuroleptic malignant syndrome, and metabolic changes such as hyperglycemia and dyslipidemia.

Metabolism and Pharmacokinetics

Brexpiprazole is metabolized primarily in the liver by the cytochrome P450 enzymes CYP3A4 and CYP2D6. It has a long elimination half-life of approximately 91 hours, allowing for once-daily dosing. The drug is excreted in both urine and feces.

Regulatory Status

Brexpiprazole is approved for use in several countries, including the United States, Canada, and Japan. It is available by prescription only and is classified as a Schedule IV controlled substance in some jurisdictions due to its potential for abuse.

Research and Development

Brexpiprazole is being investigated for other potential therapeutic uses, including the treatment of bipolar disorder, post-traumatic stress disorder (PTSD), and agitation associated with Alzheimer's disease.

Also see

• Atypical antipsychotic
• Serotonin-dopamine activity modulator
• Schizophrenia
• Major depressive disorder