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 [H-3] quipazine was displaced by ICS 205-930, GR 38032F and S 11978 with K(I) values of 2.25 nM, 36.5 nM and 1.75 nM respectively. Electrophysiological studies showed that S11978 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.