Harada Y, Hara H, Sukamoto T
Department of Pharmacology, New Drug Research Laboratories, Kanebo, Ltd., Osaka, Japan.
Eur J Pharmacol. 1994 Aug 11;261(1-2):91-6. doi: 10.1016/0014-2999(94)90305-0.
We examined the effects of KB-5492, 4-methoxyphenyl 4-(3,4,5-trimethoxybenzyl)-1-piperazine acetate monofumarate monohydrate, a novel anti-ulcer agent and a selective sigma receptor ligand, on specific 3H-N-allyl-normetazocine (SKF 10,047) and [3H]1,3-di(2-tolyl)guanidine (DTG) binding in porcine gastric fundic mucosa. KB-5492 inhibited specific 3H-SKF 10,047 binding in a competitive manner and specific [3H]DTG binding in a non-competitive manner. The Ki value of KB-5492 on specific [3H]DTG binding (Ki = 4.6 microM) was 8.4-fold higher than that on specific 3H-SKF 10,047 binding (Ki = 0.55 microM). Computer-assisted analysis of the displacement curve of KB-5492 for specific [3H]DTG binding indicated the best fit for a two-site model rather than a one-site model, but not for specific 3H-SKF 10,047 binding. Anti-ulcer agents such as omeprazole, cetraxate, cimetidine, sofalcone, sucralfate, teprenone and troxipide had weak or little effect on specific 3H-SKF 10,047 and [3H]DTG binding at a concentration of 100 microM, except that omeprazole exhibited a low affinity for specific 3H-SKF 10,047 binding. These findings suggest that KB-5492 is a unique anti-ulcer agent which binds to sigma receptors in porcine gastric fundic mucosa.
我们研究了新型抗溃疡药物、选择性σ受体配体KB-5492（4-甲氧基苯基4-(3,4,5-三甲氧基苄基)-1-哌嗪乙酸单富马酸盐一水合物）对猪胃底黏膜中特异性3H-N-烯丙基去甲美沙酮（SKF 10,047）和[3H]1,3-二(2-甲苯基)胍（DTG）结合的影响。KB-5492以竞争性方式抑制特异性3H-SKF 10,047结合，以非竞争性方式抑制特异性[3H]DTG结合。KB-5492对特异性[3H]DTG结合的Ki值（Ki = 4.6 microM）比对特异性3H-SKF 10,047结合的Ki值（Ki = 0.55 microM）高8.4倍。计算机辅助分析KB-5492对特异性[3H]DTG结合的置换曲线表明，其最适合双位点模型而非单位点模型，但对特异性3H-SKF 10,047结合不适合。奥美拉唑、西曲酸酯、西咪替丁、索法酮、硫糖铝、替普瑞酮和曲昔匹特等抗溃疡药物在100 microM浓度下对特异性3H-SKF 10,047和[3H]DTG结合的影响较弱或几乎没有影响，不过奥美拉唑对特异性3H-SKF 10,047结合表现出低亲和力。这些发现表明，KB-5492是一种独特的抗溃疡药物，可与猪胃底黏膜中的σ受体结合。
