S 14297, a novel selective ligand at cloned human dopamine D3 receptors, blocks 7-OH-DPAT-induced hypothermia in rats

Eur J Pharmacol. 1994 Aug 1;260(2-3):R3-5. doi: 10.1016/0014-2999(94)90353-0.

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

  • 2-Naphthylamine / administration & dosage
  • 2-Naphthylamine / analogs & derivatives*
  • 2-Naphthylamine / metabolism
  • 2-Naphthylamine / pharmacology
  • 2-Naphthylamine / therapeutic use
  • Animals
  • Binding, Competitive
  • Body Temperature / drug effects*
  • CHO Cells / drug effects
  • CHO Cells / metabolism
  • Cloning, Molecular
  • Cricetinae
  • Cricetulus
  • Furans / administration & dosage
  • Furans / metabolism
  • Furans / pharmacology*
  • Furans / therapeutic use
  • Humans
  • Hypothermia / chemically induced
  • Hypothermia / drug therapy*
  • Ligands
  • Male
  • Rats
  • Rats, Wistar
  • Receptors, Dopamine / chemistry
  • Receptors, Dopamine / metabolism*
  • Receptors, Dopamine D2*
  • Receptors, Dopamine D3
  • Recombinant Proteins / metabolism
  • Tetrahydronaphthalenes / metabolism
  • Tetrahydronaphthalenes / toxicity*
  • Transfection

Substances

  • DRD3 protein, human
  • Drd3 protein, rat
  • Furans
  • Ligands
  • Receptors, Dopamine
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • Recombinant Proteins
  • Tetrahydronaphthalenes
  • 7-(N,N-dipropylamino)-5,6,7,8-tetrahydronaphtho(2,3-b)dihydro-2,3-furan
  • 2-Naphthylamine
  • 7-hydroxy-2-N,N-dipropylaminotetralin