Brexpiprazole (Rexulti®): A Comprehensive Pharmacological and Clinical Review

[Section 1: Executive Summary & Introduction]

1.1 Overview

Brexpiprazole is a second-generation, or atypical, antipsychotic agent developed through a collaboration between Otsuka Pharmaceutical Co., Ltd. and H. Lundbeck A/S.[1] It is pharmacologically classified as a Serotonin-Dopamine Activity Modulator (SDAM), a designation that reflects its unique and complex mechanism of action involving partial agonism and antagonism at key neurotransmitter receptors.[4] Administered as a once-daily oral tablet, brexpiprazole represents a significant therapeutic option in the management of several complex psychiatric disorders.[8]

1.2 Clinical Context and Positioning

Brexpiprazole is a structural analogue of aripiprazole and is widely considered its therapeutic successor.[10] Its development was a deliberate effort in medicinal chemistry to refine the pharmacodynamic profile of aripiprazole, with the specific goal of potentially improving tolerability while maintaining or enhancing efficacy.[4] The key molecular modifications were intended to reduce intrinsic activity at the dopamine D₂ receptor and increase affinity and antagonism at serotonin 5-HT₂ₐ receptors.[4] This refined pharmacology was hypothesized to mitigate the risk of certain adverse effects, most notably akathisia, a common and distressing side effect associated with D₂ partial agonism.[4]