Certain D(2)-like dopamine receptor (DR) agonists are useful therapeutically as antiparkinsonian drugs, whereas D(2)-like DR antagonists or partial agonists are proven effective as antipsychotics. Two isoquinoline derivatives, 1-(2'-bromobenzyl)-6,7-dihydroxy-N-methyl-tetrahydroisoquinoline (Br-BTHIQ, 1) and 1,2-demethyl-nuciferine (aporphine, 2), were herein synthesized, and their dopaminergic affinity in cloned human D(2)R, D(3)R, and D(4)R subtypes and their behavior as agonists/antagonists were evaluated. They showed affinity values (K(i)) for hD(2), hD(3), and hD(4) DR within the nanomolar range. The trends in affinity were hD(4)R >> hD(3)R > hD(2)R for Br-BTHIQ (1) and hD(2)R > hD(4)R > hD(3)R for 1,2-demethyl-nuciferine (2). The functional assays of cyclic adenosine monophosphate signaling at human D(2)R showed a partial agonist effect for Br-BTHIQ (1) and full agonist behavior for aporphine (2), with half maximal effective concentration values of 2.95 and 10.2 muM, respectively. Therefore, both isoquinolines 1 and 2 have emerged as lead molecules for the synthesis of new therapeutic drugs that ultimately may be useful to prevent schizophrenia and Parkinson's disease, respectively.