Antiallergic effect of 1-(2-ethoxyethyl)-2-(4-methyl-1-homopiperazinyl)benzimidaz ole difumarate (KB-2413)

Arzneimittelforschung. 1984;34(7):805-10.

Abstract

Antiallergic effects of 1-(2-ethoxyethyl)-2-(4-methyl-1-homopiperazinyl)benzimidazol e difumarate (KB-2413) were investigated in immediate type hypersensitivities. KB-2413 (0.005-0.04 mg/kg p.o.) showed a marked inhibition on lethal anaphylaxis in guinea pigs induced by anti-egg albumin rabbit serum, and it was 30 and 1.6 times more potent than chlorpheniramine and ketotifen, respectively. KB-2413 (0.003-0.1 mg/kg p.o.) showed a dose-dependent inhibition on vascular permeability increase induced by 48 h homologous passive cutaneous anaphylaxis (PCA) and histamine in guinea pigs, being about 10-30 times and 3 times more potent than chlorpheniramine and ketotifen, respectively. All drugs did not completely inhibit 4 h heterologous PCA in guinea pigs induced by the anti-egg albumin rabbit serum in the doses used here, but KB-2413 was more effective than chlorpheniramine and ketotifen. No difference in inhibitory effect on the vascular permeability increase between the single and daily oral administration for 4 weeks of KB-2413 could be found. KB-2413, as well as chlorpheniramine and ketotifen, showed a dose-dependent inhibition on 48 h homologous PCA in rats at doses of 1-10 mg/kg p.o., and showed a concentration-dependent inhibition on Schultz-Dale reaction at 10(-8) - 10(-7) mol/l. KB-2413 (10(-5) - 10(-3) mol/l) showed a concentration-dependent inhibition of anaphylactic histamine release from isolated rat peritoneal mast cells which were passively sensitized by rat IgE. KB-2413 also inhibited compound 48/80-induced histamine release from rat peritoneal mast cells.(ABSTRACT TRUNCATED AT 250 WORDS)

MeSH terms

  • Anaphylaxis / prevention & control
  • Animals
  • Benzimidazoles / pharmacology*
  • Capillary Permeability / drug effects
  • Guinea Pigs
  • Histamine / pharmacology
  • Histamine H1 Antagonists / therapeutic use*
  • Histamine Release / drug effects
  • Hypersensitivity / drug therapy*
  • Immunoglobulin E / physiology
  • In Vitro Techniques
  • Lung / metabolism
  • Male
  • Mast Cells / drug effects
  • Passive Cutaneous Anaphylaxis / drug effects
  • Rabbits
  • Rats
  • Rats, Inbred Strains
  • Serotonin / pharmacology
  • p-Methoxy-N-methylphenethylamine / pharmacology

Substances

  • Benzimidazoles
  • Histamine H1 Antagonists
  • Serotonin
  • Immunoglobulin E
  • p-Methoxy-N-methylphenethylamine
  • Histamine
  • emedastine