S 11978对N1E - 115神经母细胞瘤细胞中5HT3受体的拮抗特性。

The antagonist properties of S 11978 on 5HT3 receptors in N1E-115 neuroblastoma cells.

作者信息

Morain P, Abraham C, Lacoste J M, Malen C, Laubie M, Giesen-Crouse E

机构信息

Institut de Recherches Servier, Suresnes, France.

出版信息

Fundam Clin Pharmacol. 1993;7(5):205-8. doi: 10.1111/j.1472-8206.1993.tb00233.x.

DOI:10.1111/j.1472-8206.1993.tb00233.x

PMID:8370567

Abstract

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.

摘要

运用放射性配体结合和全细胞膜片钳技术，在N1E-115小鼠神经母细胞瘤×大鼠胶质瘤杂交细胞中检测新型拮抗剂S 11978（内-7-[(8-甲基-8-氮杂双环[3,2,1]-3-辛基)氧羰基]苯并[b]噻吩）对5HT3受体的作用。5HT3受体配体[3H]喹哌嗪被ICS 205-930、GR 38032F和S 11978取代，其KI值分别为2.25 nM、36.5 nM和1.75 nM。电生理学研究表明，S 11978是一种强效的5HT3拮抗剂：在-65 mV的钳制电位下，ICS 205-930、GR 38032F和S 11978抑制5HT诱导的内向电流的IC50值分别为0.22 nM、0.63 nM和0.43 nM。结论是S 11978是一种强效、高亲和力的5HT3受体拮抗剂。