H. Lundbeck A/S, Department of Medicinal Chemistry & DMPK, Ottiliavej 9, DK-2500 Valby, Denmark.
Curr Pharm Des. 2011;17(2):137-50. doi: 10.2174/138161211795049624.
Disturbances of the basal ganglia processes is heavily involved in schizophrenia. Phosphodiesterase 10A (PDE10A) is a basal ganglia specific hydrolase, which plays an essential role in regulating cAMP/PKA and cGMP/PKG signalling cascades by controlling the magnitude, duration and cellular location of cAMP/cGMP elevation. Biochemical and behavioral data indicate that PDE10A inhibition activates cAMP/PKA signalling in the basal ganglia, leading to the potentiation of dopamine D₁ receptor signalling, and concomitant inhibition of dopamine D₂ receptor signalling. Preclinical evidence in a range of animal models suggests that a PDE10A inhibitor could provide efficacy on positive, cognitive and negative symptoms of schizophrenia and PDE10A inhibitors are currently being evaluated in clinical trials for the treatment of schizophrenia.
基底神经节过程的紊乱与精神分裂症密切相关。磷酸二酯酶 10A（PDE10A）是一种基底神经节特异性水解酶，通过控制 cAMP/cGMP 升高的幅度、持续时间和细胞位置，在调节 cAMP/PKA 和 cGMP/PKG 信号级联中起着至关重要的作用。生化和行为数据表明，PDE10A 抑制可激活基底神经节中的 cAMP/PKA 信号，导致多巴胺 D₁受体信号增强，同时抑制多巴胺 D₂受体信号。一系列动物模型的临床前证据表明，PDE10A 抑制剂可能对精神分裂症的阳性、认知和阴性症状有效，目前正在临床试验中评估 PDE10A 抑制剂治疗精神分裂症的效果。
