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: Y Harada, H Hara, T Sukamoto
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 261 Issue 1-2 Pg. 91-6 (Aug 11 1994) ISSN: 0014-2999 [Print] Netherlands
• PMID: 8001658 (Publication Type: Journal Article)

Chemical References

• Anti-Ulcer Agents
• Guanidines
• Piperazines
• Receptors, sigma
• KB 5492
• 1,3-ditolylguanidine

Topics

• Animals
• Anti-Ulcer Agents (metabolism)
• Binding, Competitive (drug effects)
• Gastric Mucosa (metabolism)
• Guanidines (metabolism)
• In Vitro Techniques
• Membranes (drug effects, metabolism)
• Piperazines (metabolism)
• Receptors, sigma (metabolism)
• Swine