Aripiprazole is an atypical antipsychotic drug behaving as a partial agonist at dopamine D₂ and 5-HT_1A receptors. It is also well known that this compound has a high affinity at 5-HT_2A receptor, and usually it is recognized as a 5-HT_2A receptor antagonist like serotonin-dopamine antagonists (SDAs). In the present study, the method of [³⁵S]GTPγS binding/immunoprecipitation assay for functional coupling of 5-HT_2A receptor to Galpha_q/11 was re-constructed using new anti-Galpha_q/11 antibody in brain membranes, and the effects of aripiprazole and brexpiprazole on this experimental system were investigated. The [³⁵S]GTPγS binding/immunoprecipitation assay for 5-HT_2A receptor-mediated Galpha_q/11 activation was successfully re-established with anti-Galpha_q/11 antibody ab75825, instead of sc-393, in both rat and human brain membranes. In rat brain membranes, aripiprazole stimulated the specific binding of [³⁵S]GTPγS to Galpha_q/11 in a concentration-dependent manner, with an EC₅₀ value of 71.3 nM (pEC₅₀ = 7.14 ± 0.31) and the %E_max of 61.5 ± 8.3 (N = 7). Brexpiprazole did not show the similar effects. Further experiments are ongoing to elucidate the receptor subtype involved in this response and to confirm whether these phenomena could be extended to human brain membranes.