title: Receptor affinities of dopamine D1 receptor-selective novel phenylbenzazepines.
abstract: We prepared a series of 18 novel substituted phenylbenzazepine congeners of the dopamine D1/D5 receptor partial-agonist SKF-83959 (R,S-3-methyl-6-chloro-7,8-dihydroxy-1-[3'-methylphenyl]-2,3,4,5-tetrahydro-1H-benzazepine) and characterized their potency and selectivity in assays of dopamine, 5-HT and adrenoceptors in rat brain tissue or membranes of genetically transfected cells. The R-enantiomer of SKF-83959 (MCL-202) and three other novel racemic 1-phenyl-7,8-dihydroxybenzazepines (MCL-204, -203, and -207) showed very high dopamine D5 receptor affinity; MCL-209 displayed the greatest dopamine D5 receptor affinity. These five potent novel ligands also had >100-fold selectivity for dopamine D1 over dopamine D2, D3, serotonin 5-HT-2A receptors and alpha2-adrenoceptors. They require further functional testing to characterize their intrinsic activity, and for potential stimulant-antagonist actions, as observed with SKF-83959 and MCL-202.
authors.affiliation: Department of Psychiatry and Neuroscience Program, Harvard Medical School, Boston, MA, USA. neumeyer@mclean.harvard.edu
authors.forename: John L
authors.initials: JL
authors.lastname: Neumeyer
authors.forename: Nora S
authors.initials: NS
authors.lastname: Kula
authors.forename: Jack
authors.initials: J
authors.lastname: Bergman
authors.forename: Ross J
authors.initials: RJ
authors.lastname: Baldessarini
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D016466:CHO Cells; D006224:Cricetinae; D006801:Humans; D008297:Male; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists* / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D001552:Benzazepines; D017447:Receptors, Dopamine D1; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; C080703:SK&F 83959