Lu AF11167

Lu AF11167 is a selective, high-affinity small molecule inhibitor of phosphodiesterase 10A (PDE10A), developed by Lundbeck for the treatment of schizophrenia. PDE10A is an enzyme highly expressed in the striatum of the brain and plays a role in modulating dopamine D1 and D2 receptor-mediated intraneuronal signaling. Unlike traditional antipsychotics that act as direct antagonists at dopamine receptors, Lu AF11167 modulates downstream synaptic transmission without binding to these receptors. The drug was investigated primarily for its potential to treat negative symptoms in patients with schizophrenia but failed to demonstrate efficacy over placebo in phase II clinical trials. Development was discontinued after interim futility analysis showed it was unlikely to meet primary endpoints[2][3][5][6].