The novel antagonist, S33084, and GR218,231 interact selectively with cloned and native, rat dopamine D(3) receptors as compared with native, rat dopamine D(2) receptors.
The novel benzopyranopyrrole, S33084 ((3aR,9bS)-N[4-(8-cyano-1,3a,4, 9b-tetrahydro-3H-benzopyrano[3,4-c]pyrrole-2-yl)-butyl] (4-phenyl)benzamide)), and the aminotetralin derivative, GR218,231 (2(R,S)-(di-n-propylamino)-6-(4-methoxyphenylsulfonylmethyl)-1,2,3 , 4-tetrahydro naphthalene), displayed high affinity at cloned, rat dopamine D(3) receptors (pK(i)s of 8.72 and 8.67, respectively), as well as dopamine D(3) receptors in rat olfactory tubercle (8.62 and 8.94, respectively). In contrast, they showed low affinities at striatal dopamine D(2) receptors (6.82 and 6.64, respectively). Unlike S33084 and GR218,231, the arylpiperazine, L741,626 (4-(4-chlorophenyl)-1-(1H-indol-3-ylmethyl)piperidin-4-ol), showed lower affinity for cloned (6.46) and native (6.92) dopamine D(3) receptors than for striatal dopamine D(2) receptors (7.52). S33084, GR218,231 and L741,626 should prove useful tools for exploration of the functional roles of dopamine D(3) vs. dopamine D(2) receptors.
Cussac
D
D
Psychopharmacology Department, Institut de Recherches Servier, Centre de Recherches de Croissy, Croissy-sur-Seine, Paris, France.
Newman-Tancredi
A
A
Sezgin
L
L
Millan
M J
MJ
D000818:Animals; D001578:Benzopyrans / Q000378:metabolism*; D001667:Binding, Competitive; D016466:CHO Cells; D006224:Cricetinae; D018492:Dopamine Antagonists / Q000378:metabolism*; D009833:Olfactory Pathways / Q000378:metabolism; D010078:Oxazines / Q000378:metabolism; D011758:Pyrroles / Q000378:metabolism*; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3; D011994:Recombinant Proteins / Q000378:metabolism; D013134:Spiperone / Q000378:metabolism; D013450:Sulfones / Q000378:metabolism*; D013764:Tetrahydronaphthalenes / Q000378:metabolism*
D001578:Benzopyrans; D018492:Dopamine Antagonists; C493595:Drd3 protein, rat; C408390:GR 218231; D010078:Oxazines; D011758:Pyrroles; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D011994:Recombinant Proteins; C408389:S 33084; D013450:Sulfones; D013764:Tetrahydronaphthalenes; C062458:3,4,4a,10b-tetrahydro-4-propyl-2H,5H-(1)benzopyrano(4,3-b)-1,4-oxazin-9-ol; D013134:Spiperone; C031349:7-hydroxy-2-N,N-dipropylaminotetralin