An overview on benzylisoquinoline derivatives with dopaminergic and serotonergic activities.
Dopamine and serotonin are important neurotransmitters in the mammalian central nervous system (CNS) involved in numerous physiological and behavioural disorders such as schizophrenia, major depression, anxiety, Parkinson's and Huntington's diseases, and attention deficit hyperactivity disorder. Several natural and synthetic benzylisoquinoline derivatives have displayed affinity for dopamine and serotonin receptors in nanomolar or micromolar ranges. This review covers the last three decades of dopaminergic and serotonergic activities, and especially focuses on structure-activity relationships of natural and synthetic benzylisoquinoline derivatives. We have included aporphines, 1-benzyltetrahydroisoquinolines, bis-benzylisoquinolines, protoberberines, cularines and other structural analogues. Further molecular modelling calculations have been considered as important tools to not only obtain structural information of both neurotransmitter receptors, but to also identify their pharmacophore features. The development of selective potential ligands like benzylisoquinoline derivatives may help in the therapy of diseases related to CNS dysfunction.
Cabedo
N
N
Centro de Ecología Química Agrícola, Universidad Politécnica de Valencia, Valencia, Spain. ncabedo@ceqa.upv.es
Berenguer
I
I
Figadère
B
B
Cortes
D
D
D044182:Benzylisoquinolines / Q000737:chemistry* / Q000494:pharmacology; D002493:Central Nervous System Diseases / Q000188:drug therapy; D018492:Dopamine Antagonists / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D018377:Neurotransmitter Agents / Q000737:chemistry* / Q000494:pharmacology; D011954:Receptors, Dopamine / Q000737:chemistry / Q000378:metabolism; D011985:Receptors, Serotonin / Q000737:chemistry / Q000378:metabolism; D012702:Serotonin Antagonists / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D044182:Benzylisoquinolines; D018492:Dopamine Antagonists; D018377:Neurotransmitter Agents; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists