title: S 14297, a novel selective ligand at cloned human dopamine D3 receptors, blocks 7-OH-DPAT-induced hypothermia in rats.
abstract: The selective dopamine D3 receptor agonist, 7-OH-DPAT ((+)-7-hydroxy-2-(di-n-propylamino)tetralin) and the novel naphthofurane, S 14297 ((+)-[7-(N,N-dipropylamino)-5,6,7,8-tetrahydro- naphtho(2,3b)dihydro,2,3-furane]), bound with high affinity and selectivity to recombinant, human dopamine D3 versus D2 receptors stably transfected into Chinese hamster ovary cells: Ki values = 2 versus 103 nM for 7-OH-DPAT and 13 versus 297 nM for S 14297. In contrast, the putative dopamine D3 receptor antagonist, AJ 76 (cis-(+)-5-methoxy-1-methyl-2-(n- propylamino)tetralin), displayed low affinity and selectivity for dopamine D3 versus D2 sites (70 versus 154 nM). 7-OH-DPAT (0.01-0.16 mg/kg s.c.) provoked hypothermia in rats, an action abolished by S 14297 (0.04-0.63 mg/kg s.c.) and, less potently, by AJ 76 (0.16-2.5 mg/kg s.c.). S 14297 (20.0 mg/kg s.c.) did not modify prolactin secretion. These data suggest that dopamine D3 receptors mediate hypothermia in the rat and that S 14297 acts as a selective antagonist at these sites.
authors.affiliation: Psychopharmacology Department, Centre de Recherches de Croissy, Crossy-sur-Seine, France.
authors.forename: M J
authors.initials: MJ
authors.lastname: Millan
authors.forename: V
authors.initials: V
authors.lastname: Audinot
authors.forename: J M
authors.initials: JM
authors.lastname: Rivet
authors.forename: A
authors.initials: A
authors.lastname: Gobert
authors.forename: J
authors.initials: J
authors.lastname: Vian
authors.forename: J F
authors.initials: JF
authors.lastname: Prost
authors.forename: M
authors.initials: M
authors.lastname: Spedding
authors.forename: J L
authors.initials: JL
authors.lastname: Peglion
mesh_terms: D015081:2-Naphthylamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001667:Binding, Competitive; D001831:Body Temperature / Q000187:drug effects*; D016466:CHO Cells / Q000187:drug effects / Q000378:metabolism; D003001:Cloning, Molecular; D006224:Cricetinae; D003412:Cricetulus; D005663:Furans / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007035:Hypothermia / Q000139:chemically induced / Q000188:drug therapy*; D008024:Ligands; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011954:Receptors, Dopamine / Q000737:chemistry / Q000378:metabolism*; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D011994:Recombinant Proteins / Q000378:metabolism; D013764:Tetrahydronaphthalenes / Q000378:metabolism / Q000633:toxicity*; D014162:Transfection
chemical_list: C493593:DRD3 protein, human; C493595:Drd3 protein, rat; D005663:Furans; D008024:Ligands; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D011994:Recombinant Proteins; D013764:Tetrahydronaphthalenes; C090812:7-(N,N-dipropylamino)-5,6,7,8-tetrahydronaphtho(2,3-b)dihydro-2,3-furan; D015081:2-Naphthylamine; C031349:7-hydroxy-2-N,N-dipropylaminotetralin