5-HT1A and D2 dual-receptor agonist( Soochow University )

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.