3,4-Dihydroxy- and 3,4-methylenedioxy- phenanthrene-type alkaloids with high selectivity for D2 dopamine receptor

Dopamine-mediated neurotransmission plays an important role in relevant psychiatric and neurological disorders. Nowadays, there is an enormous interest in the development of new drugs acting at the dopamine receptors (DR) as potential new targets for the treatment of schizophrenia or Parkinson’s disease. Previous studies have revealed that isoquinoline compounds such as tetrahydroisoquinolines (THIQs) can behave as selective D₂ dopaminergic alkaloids. In the present study we have synthesized five aporphine compounds and five phenanthrene alkaloids and evaluated their potential dopaminergic activity. Binding studies on rat striatal membranes were used to evaluate their affinity and selectivity towards D₁ and D₂ DR. Phenanthrene type alkaloids, in particular the 3,4-dihydroxy- and 3,4-methylenedioxy derivatives, displayed high selectivity towards D₂ DR. Therefore, they are potential candidates to be used in the treatment of schizophrenia (antagonists) or Parkinson’s disease (agonists) due to their scarce D₁ DR-associated side effects.