Identification of <i>N</i>-Propylnoraporphin-11-yl 5-(1,2-Dithiolan-3-yl)pentanoate as a New Anti-Parkinson's Agent Possessing a Dopamine D<sub>2</sub> and Serotonin 5-HT<sub>1A</sub> 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 (−)-<b>15</b> was identified as a full agonist at the dopamine D<sub>2</sub> and serotonin 5-HT<sub>1A</sub> receptors with <i>K</i><sub>i</sub> values of 174 and 66 nM, respectively. It elicited antiparkinsonian action on Parkinsin’s disease (PD) rats with minor dyskinesia. Chronic use of (−)-<b>15</b> reduced l-DOPA-induced dyskinesia (LID) without attenuating the antiparkinsonian effect. These results suggest that 5-HT<sub>1A</sub> and D<sub>2</sub> dual-receptor agonist (−)-<b>15</b> may present a novel candidate drug in the treatment of PD and LID.