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1-(2'-Bromobenzyl)-6,7-dihydroxy-N-methyl-tetrahydroisoquinoline and 1,2-Demethyl-nuciferine as Agonists in Human D2 Dopamine Receptors.
Silva, Andrea G; Vila, Laura; Marques, Patrice; Moreno, Laura; Loza, Mabel; Sanz, María-Jesús; Cortes, Diego; Castro, Marián; Cabedo, Nuria.
Afiliação
  • Silva AG; Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), Department of Pharmacology , Universidad de Santiago de Compostela , 15782 Santiago de Compostela , Spain.
  • Vila L; Institute of Health Research (INCLIVA) , University Clinic Hospital of Valencia , 46010 Valencia , Spain.
  • Marques P; Institute of Health Research (INCLIVA) , University Clinic Hospital of Valencia , 46010 Valencia , Spain.
  • Moreno L; Department of Pharmacology, Faculty of Pharmacy , University of Valencia , 46100 Valencia , Spain.
  • Loza M; Department of Pharmacology, Faculty of Medicine , University of Valencia , 46010 Valencia , Spain.
  • Sanz MJ; Department of Pharmacology, Faculty of Pharmacy , University of Valencia , 46100 Valencia , Spain.
  • Cortes D; Department of Pharmacology, Faculty of Medicine , University of Valencia , 46010 Valencia , Spain.
  • Castro M; Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), Department of Pharmacology , Universidad de Santiago de Compostela , 15782 Santiago de Compostela , Spain.
  • Cabedo N; Institute of Health Research (INCLIVA) , University Clinic Hospital of Valencia , 46010 Valencia , Spain.
J Nat Prod ; 83(1): 127-133, 2020 01 24.
Article em En | MEDLINE | ID: mdl-31933369
Certain D2-like dopamine receptor (DR) agonists are useful therapeutically as antiparkinsonian drugs, whereas D2-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 D2R, D3R, and D4R subtypes and their behavior as agonists/antagonists were evaluated. They showed affinity values (Ki) for hD2, hD3, and hD4 DR within the nanomolar range. The trends in affinity were hD4R ≫ hD3R > hD2R for Br-BTHIQ (1) and hD2R > hD4R > hD3R for 1,2-demethyl-nuciferine (2). The functional assays of cyclic adenosine monophosphate signaling at human D2R 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 µM, 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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Aporfinas / AMP Cíclico / Agonistas de Dopamina / Tetra-Hidroisoquinolinas Limite: Animals / Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Aporfinas / AMP Cíclico / Agonistas de Dopamina / Tetra-Hidroisoquinolinas Limite: Animals / Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article