The antagonist properties of S 11978 on 5HT3 receptors in N1E-115 neuroblastoma cells.
The effects of the novel antagonist S 11978 (Endo-7-[(8-methyl-8-azabicyclo[3,2,1]-3-octyl)oxycarbonyl] benzo[b] thiophene) on 5HT3 receptors were examined in N1E-115 mouse neuroblastoma x rat glioma hybrid cells, with radioligand binding and whole cell patch clamp techniques. The 5HT3 receptor ligand [3H] quipazine was displaced by ICS 205-930, GR 38032F and S 11978 with KI values of 2.25 nM, 36.5 nM and 1.75 nM respectively. Electrophysiological studies showed that S 11978 is a potent 5HT3 antagonist: IC50 values for inhibition of 5HT-induced inward current by ICS 205-930, GR 38032F and S 11978 were 0.22 nM, 0.63 nM and 0.43 nM respectively at a holding potential of -65 mV. It is concluded that S 11978 is a potent, high affinity 5HT3 receptor antagonist.
Morain
P
P
Institut de Recherches Servier, Suresnes, France.
Abraham
C
C
Lacoste
J M
JM
Malen
C
C
Laubie
M
M
Giesen-Crouse
E
E
D000818:Animals; D001667:Binding, Competitive; D004594:Electrophysiology; D007211:Indoles / Q000378:metabolism / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D009447:Neuroblastoma / Q000188:drug therapy / Q000648:ultrastructure*; D017294:Ondansetron / Q000378:metabolism / Q000494:pharmacology; D011814:Quipazine / Q000378:metabolism; D012702:Serotonin Antagonists; D013876:Thiophenes / Q000494:pharmacology*; D014316:Tritium; D000077526:Tropisetron; D014407:Tumor Cells, Cultured / Q000187:drug effects
D007211:Indoles; C083093:S 11978; D012702:Serotonin Antagonists; D013876:Thiophenes; D014316:Tritium; D017294:Ondansetron; D011814:Quipazine; D000077526:Tropisetron