Ibogaine is a psychoactive indole alkaloid with high affinity for several targets including the ₂ receptor. Indeed, extensive data support the involvement of the ₂ receptor in neurological disorders, including Alzheimer's disease, schizophrenia, alcohol abuse and pain. Due to its serious side effects which prevent ibogaine from potential clinical applications, novel ibogaine derivatives endowed with improved ₂ receptor affinity may be particularly beneficial. With the purpose to facilitate the investigation of iboga alkaloid derivatives which may serve as templates for the design of selective ₂ receptor ligands, here we report a deconstruction study on the ibogaine tricyclic moiety and a successive scaffold-hopping of the indole counterpart. A 3D-QSAR model has been applied to predict the ₂ p values of the new compounds, whereas a molecular docking study conducted upon the ₂ receptor built by homology modeling was used to further validate the best-scored molecules. We eventually evaluated pinoline, a carboline derivative, for ₂ receptor affinity through radioligand binding assay and the results confirmed the predicted high µM range of affinity and good selectivity. The obtained results could be helpful in the drug design process of new ibogaine simplified analogs with improved ₂ receptor binding capabilities.