title: Binding properties of KB-5492, a novel anti-ulcer agent, at sigma receptors in porcine gastric fundic mucosa.
abstract: 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.
authors.affiliation: Department of Pharmacology, New Drug Research Laboratories, Kanebo, Ltd., Osaka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Harada
authors.forename: H
authors.initials: H
authors.lastname: Hara
authors.forename: T
authors.initials: T
authors.lastname: Sukamoto
mesh_terms: D000818:Animals; D000897:Anti-Ulcer Agents / Q000378:metabolism*; D001667:Binding, Competitive / Q000187:drug effects; D005753:Gastric Mucosa / Q000378:metabolism*; D006146:Guanidines / Q000378:metabolism; D066298:In Vitro Techniques; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D010879:Piperazines / Q000378:metabolism*; D017480:Receptors, sigma / Q000378:metabolism*; D013552:Swine
chemical_list: D000897:Anti-Ulcer Agents; D006146:Guanidines; D010879:Piperazines; D017480:Receptors, sigma; C065167:KB 5492; C050232:1,3-ditolylguanidine