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**LU AF11167 + risperidone** is a combination of two drugs: LU AF11167, a selective high-affinity inhibitor of phosphodiesterase 10A (PDE10A), and risperidone, a second-generation antipsychotic agent. LU AF11167 modulates dopamine D1 and D2 receptor-mediated intraneuronal signaling in neurons—*without direct receptor binding*—and was developed to address *negative symptoms of schizophrenia* by influencing dopamine pathway activity. Risperidone inhibits dopaminergic D2 and serotonergic 5-HT2A receptors, reducing positive and negative symptoms of schizophrenia, as well as symptoms of other mental disorders. The combination aims at synergistically managing persistent negative symptoms in schizophrenia. Clinical studies indicate that LU AF11167 did not provide significant additional benefit versus placebo when added to standard therapy, and its clinical trials were discontinued for futility[1][6]. The safety profile was acceptable.
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