镇学初教授课题组在Journal of Medicinal Chemistry上发表研究论文

Identification of N-Propylnoraporphin-11-yl 5-(1,2-Dithiolan-3-yl)pentanoate as a New Anti-Parkinson's Agent Possessing a Dopamine D2 and Serotonin 5-HT1A Dual-Agonist Profile

Hai Zhang, Na Ye, Shanglin Zhou, Lin Guo, Longtai Zheng, Zhili Liu, Bo Gao, Xuechu Zhen, Ao Zhang
J. Med. Chem. 2011, 54, 4324–4338

ABSTRACT: 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 D2 and serotonin 5-HT1A receptors with Ki 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-HT1A and D2 dual-receptor agonist (—)-15 may present a novel candidate drug in the treatment of PD and LID.