title: Pramipexole binding and activation of cloned and expressed dopamine D2, D3 and D4 receptors.
abstract: Pramipexole (SND 919; 2-amino-4,5,6,7-tetrahydro-6-propylamino-benzthiazole-dihydrochlor ide) is a potent dopamine autoreceptor agonist. We have carried out an analysis of the binding affinities of dopamine D2L, D2S, D3, and D4 receptors for pramipexole using both [3H]pramipexole and [3H]spiperone as radioligands at cloned and heterologously expressed receptors. Studies were carried out using rat and human D2L, D2S and D3 receptors with equivalent results. When the binding of pramipexole to the high affinity, guanine nucleotide-sensitive state of each receptor was analyzed, pramipexole is most selective for D3 compared to D2 and D4 receptors. These results indicate a 5-fold selectivity of pramipexole for D3 receptors, while quinpirole and bromocriptine are non-selective or more D2/D4 receptor selective. Two measurements of receptor activation for dopamine D2, D3, and D4 receptors also show that pramipexole is most potent for activation of D3 receptors. The dopamine D3 receptor selectivity of pramipexole may explain the previously described properties of this drug, including its potent autoreceptor preference.
authors.affiliation: Department of Biochemical Research, Boehringer-Ingelheim KG, Ingelheim, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Mierau
authors.forename: F J
authors.initials: FJ
authors.lastname: Schneider
authors.forename: H A
authors.initials: HA
authors.lastname: Ensinger
authors.forename: C L
authors.initials: CL
authors.lastname: Chio
authors.forename: M E
authors.initials: ME
authors.lastname: Lajiness
authors.forename: R M
authors.initials: RM
authors.lastname: Huff
mesh_terms: D000818:Animals; D052160:Benzothiazoles; D001667:Binding, Competitive; D016466:CHO Cells; D002478:Cells, Cultured; D006224:Cricetinae; D018491:Dopamine Agonists / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D000077487:Pramipexole; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D050638:Receptors, Dopamine D4; D013134:Spiperone / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D052160:Benzothiazoles; C493593:DRD3 protein, human; C493599:DRD4 protein, human; D018491:Dopamine Agonists; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013844:Thiazoles; D050638:Receptors, Dopamine D4; D013134:Spiperone; D000077487:Pramipexole