The naphtosultam derivative RP 62203 (fananserin) has high affinity for the dopamine D4 receptor.
The dopamine D4 receptor is a potential target for novel antipsychotic drugs. Most available compounds with affinity for the dopamine D4 receptor also bind to dopamine D2 receptors. This report describe the affinity of the 5-HT2A receptor antagonist RP 62203 (fananserin) for the human dopamine D4 receptor. Fananserin displaces [3H]spiperone binding to recombinant human dopamine D4 receptors with a Ki of 2.93 nM. This compares with an affinity (Ki) of 0.37 nM for the rat 5-HT2A receptor and of 726 mM for the rat dopamine D2 receptor. [3H]Fananserin can be used to label the recombinant dopamine D4 receptor expressed in Chinese hamster ovary cells with a KD of 0.725 nM. Fananserin is, thus, the first compound to be reported that distinguishes between dopamine D4 and D2 receptors.
Heuillet
E
E
Biology Department, Rhône Poulenc Rorer, Vitry-sur-Seine, France.
Petitet
F
F
Mignani
S
S
Malleron
J L
JL
Lavayre
J
J
Néliat
G
G
Doble
A
A
Blanchard
J C
JC
D000818:Animals; D001667:Binding, Competitive; D016466:CHO Cells; D006224:Cricetinae; D003499:Cyclic S-Oxides / Q000378:metabolism*; D006801:Humans; D008297:Male; D009281:Naphthalenes / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050638:Receptors, Dopamine D4; D011985:Receptors, Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000378:metabolism*
D003499:Cyclic S-Oxides; C493599:DRD4 protein, human; C493601:Drd4 protein, rat; D009281:Naphthalenes; D044402:Receptor, Serotonin, 5-HT2A; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D050638:Receptors, Dopamine D4; C070475:fananserin