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.
MeSH terms
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2-Naphthylamine / administration & dosage
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2-Naphthylamine / analogs & derivatives*
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2-Naphthylamine / metabolism
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2-Naphthylamine / pharmacology
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2-Naphthylamine / therapeutic use
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Animals
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Binding, Competitive
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Body Temperature / drug effects*
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CHO Cells / drug effects
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CHO Cells / metabolism
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Cloning, Molecular
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Cricetinae
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Cricetulus
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Furans / administration & dosage
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Furans / metabolism
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Furans / pharmacology*
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Furans / therapeutic use
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Humans
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Hypothermia / chemically induced
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Hypothermia / drug therapy*
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Ligands
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Male
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Rats
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Rats, Wistar
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Receptors, Dopamine / chemistry
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Receptors, Dopamine / metabolism*
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Receptors, Dopamine D2*
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Receptors, Dopamine D3
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Recombinant Proteins / metabolism
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Tetrahydronaphthalenes / metabolism
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Tetrahydronaphthalenes / toxicity*
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Transfection
Substances
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DRD3 protein, human
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Drd3 protein, rat
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Furans
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Ligands
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Receptors, Dopamine
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Receptors, Dopamine D2
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Receptors, Dopamine D3
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Recombinant Proteins
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Tetrahydronaphthalenes
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7-(N,N-dipropylamino)-5,6,7,8-tetrahydronaphtho(2,3-b)dihydro-2,3-furan
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2-Naphthylamine
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7-hydroxy-2-N,N-dipropylaminotetralin