WAY-100635 has high selectivity for serotonin 5-HT(1A) versus dopamine D(4) receptors.
The serotonin 5-HT(1A) receptor antagonist WAY-100635 was recently reported to have potent agonist properties at dopamine D(4) receptors (Chemel et al., 2006, Psychopharmacology 188, 244-251.). Herein WAY-100635 (pK(i) at human (h) serotonin 5-HT(1A) receptors=9.51; pK(i) at dopamine hD(4.4) receptors=7.42) stimulated [(35)S]GTPgammaS incorporation in membranes of Chinese Hamster Ovary cells expressing dopamine hD(4.4) receptors with only moderate potency and modest efficacy (pEC(50)=6.63; E(max)=19% of dopamine). Moreover, in antagonism experiments, WAY-100635 had a much lower potency at dopamine hD(4.4) receptors (pK(B)=7.09), than at serotonin h5-HT(1A) receptors (pK(B)=9.47). These data demonstrate that WAY-100635 has high selectivity for serotonin h5-HT(1A)versus dopamine hD(4.4) receptors.
Martel
Jean-Claude
JC
Division of Neurobiology 2 Centre de recherche Pierre Fabre, 17 avenue Jean Moulin, 81106 Castres cedex, France. jean.claude.martel@pierre-fabre.com
Leduc
Nathalie
N
Ormière
Anne-Marie
AM
Faucillon
Valérie
V
Danty
Nathalie
N
Culie
Charlène
C
Cussac
Didier
D
Newman-Tancredi
Adrian
A
D000818:Animals; D001667:Binding, Competitive; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D010879:Piperazines / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D011869:Radioligand Assay; D050638:Receptors, Dopamine D4 / Q000819:agonists / Q000378:metabolism*; D044263:Receptors, Serotonin, 5-HT1 / Q000378:metabolism*; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology*
D010879:Piperazines; D011725:Pyridines; D044263:Receptors, Serotonin, 5-HT1; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists; D050638:Receptors, Dopamine D4; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide