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
2011-07-14T00:00:00Z (GMT) by
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.