Histamine H2-Receptor Antagonism of T-593, an Anti-ulcer Agent: Studies on Aminopyrine Accumulation in Isolated Canine Gastric Mucosal Cells.

• Inoie Masukazu

  Research Laboratories, Toyama Chemical Co., Ltd.

• Marubuchi Shigeki

  Research Laboratories, Toyama Chemical Co., Ltd.

• Arai Hirotoshi

  Research Laboratories, Toyama Chemical Co., Ltd.

Bibliographic Information

Other Title

• Histamine H2-Receptor Antagonism of T-5

Abstract

Histamine H₂-receptor antagonistic properties of the anti-ulcer agent T-593, (±)-(E)-1-[2hydroxy-2-(4-hydroxyphenyl)ethyl]-3-[2[[[5-(methylamino)methyl-2-furyl]methyl]thio]ethyl]-2-(methylsulfonyl)guanidine, were investigated on [¹⁴C]aminopyrine accumulation in isolated canine gastric mucosal cells and compared with those of ranitidine and famotidine. The potency of T-593-inhibition of [¹⁴C]aminopyrine accumulation stimulated by 10^-4 M histamine, with an IC₅₀ value of 1.85× 10^-6 M, was approximately 5 times greater than that of ranitidine, but half that of famotidine. T-593 did not affect [¹⁴C]aminopyrine accumulation stimulated by carbachol or dibutyryl-cAMP. T-593 depressed the maximal response of the histamine concentration-response curve with a dose-related displacement to the right, indicating that the nature of the H₂-receptor antagonism of T-593 was insurmountable and included noncompetitive inhibition. The inhibitory efficacy of T-593 was time-dependent and was retained after the cells were washed. The inhibitory potency of (-)-S-T-593, one of the enantiomers, on the [¹⁴C]aminopyrine accumulation stimulated by histamine was approximately twice that of racemic T-593 and it also behaved as an insurmountable H₂-receptor antagonist. However, the potency of (+)-R-T-593 was markedly weak. These results suggest that T-593 has H₂-receptor antagonism that is insurmountable and this agent slowly associates and dissociates with the receptor in isolated canine gastric mucosal cells and that the specific substance causing H₂-receptor antagonism is (-)-S-T-593.

Journal

• The Japanese Journal of Pharmacology

  The Japanese Journal of Pharmacology 78 (3), 313-322, 1998

  The Japanese Pharmacological Society

Keywords

• T-593
• Histamine H<SUB>2</SUB>-antagonist
• Insurmountable antagonism
• Canine gastric mucosal cell
• Aminopyrine accumulation

Details

• CRID: 1390282679262753792
• NII Article ID: 10008681223
• NII Book ID: AA00691188
• DOI: 10.1254/jjp.78.313
• COI: 1:CAS:528:DyaK1cXnslyktLs%3D
• ISSN: 13473506
• ISSN: 00215198
• NDL BIB ID: 4610820
• PubMed: 9869265
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I4610820
• Web Site: https://api.elsevier.com/content/article/PII:S0021519819310303?httpAccept=text/xml
• Web Site: https://api.elsevier.com/content/article/PII:S0021519819310303?httpAccept=text/plain
• Web Site: https://www.jstage.jst.go.jp/article/jjp/78/3/78_3_313/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/1999087244
• Text Lang: en
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
• Abstract License Flag: Disallowed