Brexpiprazole (Rexulti®) is the second
antipsychotic agent in the world with
dopamine D2 receptor partial agonist which was developed by Otsuka Pharmaceutical Co. Ltd. It is categorized as 〝Serotonin-
dopamine Activity Modulator (SDAM)〟 that regulates both serotoninergic and dopaminergic systems by acting as a partial agonist for
serotonin 5-HT1A receptors and D2 receptors and as an antagonist for 5-HT2A receptors. In preclinical pharmacological studies,
brexpiprazole showed the equivalent
antipsychotic-like effects to those of other atypical
antipsychotics. And it was suggested that
brexpiprazole has the low potentials to induce extrapyramidal symptoms,
hyperprolactinemia and
tardive dyskinesia, with improvement effects on
cognitive dysfunction. Furthermore,
brexpiprazole has the weak effects on
histamine H1 receptors which are associated with sedation and
weight gain in clinical. In the clinical trials in patients with
schizophrenia in both acute and maintenance phase,
brexpiprazole showed improvement of
antipsychotic effects against placebo, and low incidence of adverse events, e.g., extrapyramidal symptoms,
hyperprolactinemia, and
weight gain, as suggested in preclinical studies. Furthermore,
brexpiprazole showed low incidence of metabolic abnormalities. In particular,
brexpiprazole showed relatively low incidences of
akathisia,
insomnia and agitation which has been commonly reported with
aripiprazole. This would be based on the pharmacological features of
brexpiprazole that is more potent antagonism at 5-HT2A receptors and D2 receptors partial agonism with lower intrinsic activity compared to those of
aripiprazole. In conclusion,
brexpiprazole could be one of the
antipsychotics with the most rational mechanism of action, and the better efficacy and safety/tolerability profiles would contribute to the treatment of patients with
schizophrenia.