title: Novel aza-analogous ergoline derived scaffolds as potent serotonin 5-HT₆ and dopamine D₂ receptor ligands.
abstract: By introducing distal substituents on a tetracyclic scaffold resembling the ergoline structure, two series of analogues were achieved exhibiting subnanomolar receptor binding affinities for the dopamine D2 and serotonin 5-HT6 receptor subtype, respectively. While the 5-HT6 ligands were antagonists, the D2 ligands displayed intrinsic activities ranging from full agonism to partial agonism with low intrinsic activity. These structures could potentially be interesting for treatment of neurological diseases such as schizophrenia, Parkinson's disease, and cognitive deficits.
authors.affiliation: Department of Drug Design and Pharmacology, The Faculty of Health and Medical Sciences, University of Copenhagen , 2 Universitetsparken, DK-2100 Copenhagen, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Krogsgaard-Larsen
authors.forename: Anders A
authors.initials: AA
authors.lastname: Jensen
authors.forename: Tenna J
authors.initials: TJ
authors.lastname: Schrøder
authors.forename: Claus T
authors.initials: CT
authors.lastname: Christoffersen
authors.forename: Jan
authors.initials: J
authors.lastname: Kehler
mesh_terms: D004873:Ergolines / Q000737:chemistry*; D006801:Humans; D008024:Ligands; D017448:Receptors, Dopamine D2 / Q000819:agonists* / Q000737:chemistry; D011985:Receptors, Serotonin / Q000737:chemistry / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000737:chemistry*
chemical_list: D004873:Ergolines; D008024:Ligands; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C097216:serotonin 6 receptor