YM-50001: a novel, potent and selective dopamine D4 receptor antagonist.
We investigated some in vitro pharmacological properties of a novel human dopamine D2-like receptor antagonist, YM-50001 [(R)-5-chloro-4-cyclopropylacarbonylamino-2-methoxy-N-[1-(3-methox ybenzyl)- 3-pyrrolidinyl]benzamide monooxalate]. Receptor binding studies revealed that YM-50001 had a potent affinity for human D4 receptors (Ki = 5.62 nM). YM-50001 displayed weak or negligible affinity for other neurotransmitter receptors including human D2 and D3 receptors. YM-50001 shifted the dopamine response curve on each human D2-like receptor subtype-mediated low-Km GTPase activity to the right. YM-50001 also exhibited good D4 selectivity with respect to D2-like receptor antagonism in the functional assay. These results indicate that YM-50001 is a novel, potent and selective D4 receptor antagonist.
Hidaka
K
K
Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Ibaraki, Japan.
Tada
S
S
Matsumoto
M
M
Ohmori
J
J
Maeno
K
K
Yamaguchi
T
T
D001549:Benzamides / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects*; D004298:Dopamine / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006220:Haloperidol / Q000494:pharmacology; D006801:Humans
C104859:(R)-5-chloro-4-cyclopropylcarbonylamino-2-methoxy-N-(1-(3-methoxybenzyl)-3-pyrrolidinyl)benzamide monooxalate; D001549:Benzamides; D018492:Dopamine Antagonists; D006220:Haloperidol; D004298:Dopamine