Successful CNS drug discovery requires a comprehensive understanding of target engagement, brain exposure, neurochemistry, and functional outcomes. We present an integrated preclinical CNS pharmacology platform combining receptor binding, pharmacokinetic assessment, in vivo microdialysis, and behavioral profiling to characterize centrally acting compounds. Using antipsychotic drugs as a case example, we demonstrate how these complementary approaches can be applied to link receptor occupancy with neurotransmitter modulation and pharmacological effects. This workflow enables robust evaluation of mechanism, exposure-response relationships, and translational biomarkers, supporting informed decision-making and de-risking progression of molecules across CNS drug discovery programs.