title: 3,4-Dihydroxy- and 3,4-methylenedioxy- phenanthrene-type alkaloids with high selectivity for D2 dopamine receptor.
abstract: 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.
authors.affiliation: Departamento de Farmacología, Laboratorio de Farmacoquímica, Facultad de Farmacia, Universidad de Valencia, Burjassot, 46100 Valencia, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Moreno
authors.forename: Nuria
authors.initials: N
authors.lastname: Cabedo
authors.forename: María Dolores
authors.initials: MD
authors.lastname: Ivorra
authors.forename: María-Jesús
authors.initials: MJ
authors.lastname: Sanz
authors.forename: Arturo López
authors.initials: AL
authors.lastname: Castel
authors.forename: M
authors.initials: M
authors.lastname: Carmen Álvarez
authors.forename: Diego
authors.initials: D
authors.lastname: Cortes
mesh_terms: D000470:Alkaloids / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D010300:Parkinson Disease / Q000188:drug therapy; D010616:Phenanthrenes / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D012559:Schizophrenia / Q000188:drug therapy
chemical_list: D000470:Alkaloids; D010616:Phenanthrenes; D017448:Receptors, Dopamine D2; C031181:phenanthrene
keywords: Aporphines; Dopamine receptors; Phenanthrene alkaloids; Structure–activity relationships