title: Affinity for dopamine D2, D3, and D4 receptors of 2-aminotetralins. Relevance of D2 agonist binding for determination of receptor subtype selectivity.
abstract: A series of 2-aminotetralins, substituted with a methoxy or a hydroxy group on the 5- or 7-position, and with varying N-alkyl or N-arylalkyl substituents, were prepared and evaluated in binding assays for human dopamine (DA) D2, D3, and D4 receptors. Some members of this series were prepared in former studies, but were never tested in vitro with single receptor subtypes, and these were examined again. None of the tested 2-aminotetralins showed high affinity for the dopamine D4 receptor. However, a number of the 2-aminotetralins showed high affinity for both the D2 and the D3 DA receptors, as exemplified by compounds 11-15 and 21-26, while some had a reasonable selectivity for the DA D3 receptors. The affinities of the 2-aminotetralins for the D21, receptor depended on the type of radioligand (agonist or antagonist) used. The agonist affinity data, obtained by using the agonist ligand [3H]N-0437, are thought to be more relevant for calculating DA receptor subtype selectivity.
authors.affiliation: Department of Medicinal Chemistry and Molecular Pharmacology, University of Groningen, The Netherlands.
authors.forename: L A
authors.initials: LA
authors.lastname: van Vliet
authors.forename: P G
authors.initials: PG
authors.lastname: Tepper
authors.forename: D
authors.initials: D
authors.lastname: Dijkstra
authors.forename: G
authors.initials: G
authors.lastname: Damsma
authors.forename: H
authors.initials: H
authors.lastname: Wikström
authors.forename: T A
authors.initials: TA
authors.lastname: Pugsley
authors.forename: H C
authors.initials: HC
authors.lastname: Akunne
authors.forename: T G
authors.initials: TG
authors.lastname: Heffner
authors.forename: S A
authors.initials: SA
authors.lastname: Glase
authors.forename: L D
authors.initials: LD
authors.lastname: Wise
mesh_terms: D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D006801:Humans; D007700:Kinetics; D010053:Ovary / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000378:metabolism*; D050637:Receptors, Dopamine D3; D050638:Receptors, Dopamine D4; D013379:Substrate Specificity; D013764:Tetrahydronaphthalenes / Q000737:chemistry / Q000378:metabolism*
chemical_list: C493593:DRD3 protein, human; C493599:DRD4 protein, human; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes; D050638:Receptors, Dopamine D4; C006561:2-aminotetralin