[3H]S33084: a novel, selective and potent radioligand at cloned, human dopamine D3 receptors.
The novel, selective dopamine D3 receptor antagonist, S33084 [(3aR,9bS)-N[4-(8-cyano- 1,3a,4,9b-tetrahydro-3H-benzopyrano[3,4-c]pyrrole-2-yl)-butyl] (4-phenyl)benzamide], was tritium-labelled to 59 Ci/mmol specific activity. Determination of association and dissociation rate constants at recombinant, human (h) D3 receptors stably expressed in Chinese hamster ovary (CHO) cells yielded a Kd value (0.16 nM) comparable to that observed in saturation binding experiments (0.17 nM). The competition binding profile of [3H]S33084 with diverse D3 receptor agonists and antagonists correlated highly (0.99) with that of [3H]spiperone. In conclusion, [3H]S33084 is a highly potent and selective radioligand at dopamine D3 receptors, which should be of considerable use for their characterisation.
Cussac
D
D
Psychopharmacology Department, Institut de Recherches Servier, Croissy-sur-Seine Paris, France. cussac@hotmail.com
Newman-Tancredi
A
A
Sezgin
L
L
Millan
M J
MJ
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D001667:Binding, Competitive; D016466:CHO Cells; D002478:Cells, Cultured; D006224:Cricetinae; D018492:Dopamine Antagonists / Q000494:pharmacology*; D006801:Humans; D011758:Pyrroles / Q000494:pharmacology*; D011869:Radioligand Assay; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D050637:Receptors, Dopamine D3; D011994:Recombinant Proteins / Q000187:drug effects / Q000378:metabolism; D013134:Spiperone / Q000494:pharmacology; D014162:Transfection; D014316:Tritium
D001578:Benzopyrans; C493593:DRD3 protein, human; D018492:Dopamine Antagonists; D011758:Pyrroles; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D011994:Recombinant Proteins; C408389:S 33084; D014316:Tritium; D013134:Spiperone