Biology Laboratory, Discovery Research, Mochida Pharmaceutical Co., Ltd., Gotemba, Japan.
Neuropsychopharmacol Rep. 2020 Jun;40(2):190-195. doi: 10.1002/npr2.12108. Epub 2020 Apr 29.
Phosphodiesterase 10A (PDE10A) inhibitors not only have antipsychotic-like effects but also cause cognitive enhancement without affecting extrapyramidal side effects in rodents, suggesting that PDE10A may be a novel approach for the treatment of schizophrenia. However, how a combination of PDE10A inhibitor with a currently available antipsychotic drug, risperidone contributes to the effect of each compound in rats remains unclear. The purpose of the present study was to examine the combination effects of MR1916 with a currently available antipsychotic drug, risperidone, in rats.
We examined the combination effects of the PDE10A inhibitor, MR1916 with risperidone on conditioned avoidance response (CAR) to assess antipsychotic-like effects in rats. We also examined them on catalepsy as extrapyramidal side effects and novel object recognition test in cognitive functions in rats.
MR1916 (0.025-0.2 mg/kg, p.o.) and risperidone (0.75-6 mg/kg, p.o.) alone attenuated the CAR in a dose-dependent manner. The combination of MR1916 (0.025 mg/kg, p.o.) with risperidone (0.75 mg/kg, p.o.) significantly enhanced the attenuation of CAR without increasing the escape failure response. At the same dosage, the cataleptic effects were not enhanced by combined treatment of MR1916 with risperidone. Furthermore, the enhancement of object recognition memory induced by MR1916 (0.3 mg/kg, p.o.) was not affected by the combination with risperidone (0.75 mg/kg, p.o.).
The combination of MR1916 with risperidone may have additive antipsychotic-like effects without affecting extrapyramidal side effects, and the cognitive-enhancing effect of MR1916 may not be interfered with the addition of risperidone.
磷酸二酯酶 10A（PDE10A）抑制剂不仅具有抗精神病作用，而且在啮齿动物中不会引起锥体外系副作用，还能增强认知能力，这表明 PDE10A 可能是治疗精神分裂症的一种新方法。然而，PDE10A 抑制剂与目前可用的抗精神病药物利培酮联合使用如何影响每种化合物在大鼠中的作用尚不清楚。本研究旨在研究 PDE10A 抑制剂 MR1916 与目前可用的抗精神病药物利培酮联合使用对大鼠条件性回避反应（CAR）的组合效应，以评估其抗精神病样作用。我们还研究了它们在大鼠锥体外系副作用和新物体识别测试中的认知功能。
我们研究了 PDE10A 抑制剂 MR1916 与利培酮联合使用对条件性回避反应（CAR）的组合效应，以评估其抗精神病样作用。我们还研究了它们在大鼠锥体外系副作用和新物体识别测试中的认知功能。
MR1916（0.025-0.2mg/kg，口服）和利培酮（0.75-6mg/kg，口服）单独使用时呈剂量依赖性减弱 CAR。MR1916（0.025mg/kg，口服）与利培酮（0.75mg/kg，口服）联合使用时，在不增加逃避失败反应的情况下，显著增强了 CAR 的减弱作用。在相同剂量下，联合治疗并未增强 MR1916 和利培酮的锥体外系作用。此外，MR1916（0.3mg/kg，口服）诱导的物体识别记忆增强不受与利培酮（0.75mg/kg，口服）联合治疗的影响。
MR1916 与利培酮联合使用可能具有相加的抗精神病样作用，而不会影响锥体外系副作用，并且 MR1916 的认知增强作用可能不会因添加利培酮而受到干扰。
