A series of new tetrahydroprotoberberine (THPB) derivatives were designed, synthesized, and tested for their binding affinity towards dopamine (D1 and D2) and serotonin (5-HT1A and 5-HT2A) receptors. Many of the THPB compounds exhibited high binding affinity and activity at the dopamine D1 receptor, as well as high selectivity for the D1 receptor over the D2, 5-HT1A, and 5-HT2A receptors. Among these, compound 19c exhibited a promising ...