Department of Pharmacology, Soochow University College of Pharmaceutical Sciences, Suzhou, China.
J Med Chem. 2011 Jul 14;54(13):4324-38. doi: 10.1021/jm200347t. Epub 2011 Jun 2.
A series of new aporphine analogues (aporlogues) were synthesized bearing a C-, N-, or O-linkage at the C11 position. Lipoic ester (-)-15 was identified as a full agonist at the dopamine D(2) and serotonin 5-HT(1A) receptors with K(i) values of 174 and 66 nM, respectively. It elicited antiparkinsonian action on Parkinsin's disease (PD) rats with minor dyskinesia. Chronic use of (-)-15 reduced L-DOPA-induced dyskinesia (LID) without attenuating the antiparkinsonian effect. These results suggest that 5-HT(1A) and D(2) dual-receptor agonist (-)-15 may present a novel candidate drug in the treatment of PD and LID.
一系列新型阿朴啡类似物（aporlogues）被合成，在 C11 位带有 C、N 或 O 键。硫辛酸酯 (-)-15 被鉴定为多巴胺 D2 和 5-羟色胺 5-HT1A 受体的完全激动剂，其 Ki 值分别为 174 和 66 nM。它对帕金森病（PD）大鼠具有抗帕金森病作用，且仅有轻微的运动障碍。(-)-15 的慢性使用减少了 L-多巴诱导的运动障碍（LID），而不减弱抗帕金森病作用。这些结果表明，5-HT1A 和 D2 双重受体激动剂 (-)-15 可能是治疗 PD 和 LID 的新型候选药物。
