UCM-1306 is a potent and orally active human dopamine D1 receptor allosteric modulator (PAM). UCM-1306 increases the endogenous dopamine (DA) maximal effect both in human and mouse D1 receptors. UCM-1306 is not only for improving motor symptoms but also for addressing the key comorbid cognitive impairment associated with long-term Parkinson's disease (PD)[1].
UCM-1306 (2-(Fluoromethoxy)-4'-(S-metlsulfonimidoyl)-1,1'-biphenyl; 1-10 μM) 以浓度-响应的方式增强 cAMP，且 EC50=60 nM。
UCM-1306 (2-(Fluoromethoxy)-4'-(S-metlsulfonimidoyl)-1,1'-biphenyl; 5 mg/kg; p.o.; C57BL/6J 小鼠) 具有良好的脑穿透性和口服可用性。血浆浓度可在 8 小时内定量，Tmax 为 0.5 小时[1]。
UCM-1306 (1 mg/kg; ip) 增强成年小鼠可卡因诱导的过度运动[1]。
UCM-1306 (1 mg/kg; ip) 有助于巩固长期记忆的形成[1]。
| Animal Model: | Adult C57BL/6J mice with cocaine-induced peractivity model[1] |
| Dosage: | 1 mg/kg; cocaine (20 mg/kg, sc) |
| Administration: | Intraperitoneal injection |
| Result: | Increased cocaine-induced perlocomotion, suggesting an in vivo potentiation of DA action at the D1R. |
| Animal Model: | Adult C57BL/6J mice |
| Dosage: | 1 mg/kg |
| Administration: | Intraperitoneal injection |
| Result: | Increased memory trace in C57BL/6J mice. |
[1]. GarcÍa-CÁrceles J, et, al. 2-(Fluoromethoxy)-4'-(S-methanesulfonimidoyl)-1,1'-biphenyl (UCM-1306), an Orally Bioavailable Positive Allosteric Modulator of the Human Dopamine D1 Receptor for Parkinson's Disease. J Med Chem. 2022 Sep 22;65(18):12256-12272.