Modulation of indole ring annulation in ergoline template: chemistry, receptor binding and in vivo pharmacology with 6-OHDA model of Parkinson’s disease

l -dopa provides symptomatic cure in Parkinson’s disease (PD); however, long-term treatment leads to the development of motor fluctuations and dyskinesia. l -dopa-sparing monotherapy involves treatment with dopamine agonists (DAs) exerting their action through dopamine receptor, which delays l -dopa treatment in PD. Cis and trans N-4-substituted-2,3,4,4a,5,6,11,11a-octahydro-1H-pyrido[3,2- a ] carbazoles were synthesized by modulating the indole ring annulations pattern of ergoline skeleton to identify novel DAs with promising antiparkinsonian activity. The compounds 16 and 20 with the Ki value of 1.31 and 1.09 nM, respectively, exhibiting D2-like activity were selected for evaluation of antiparkinsonian activity in 6-OHDA-induced unilateral lesioned rat model. Persuasively, both compounds 16 and 20 showed antiparkinsonian activity in a dose-dependant manner and slightly longer duration of action as compared to apomorphine.