Antiallergic effect of 1-(2-ethoxyethyl)-2-(4-methyl-1-homopiperazinyl)benzimidaz ole difumarate (KB-2413).
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)
D000707:Anaphylaxis / Q000517:prevention & control; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000627:therapeutic use*; D006636:Histamine Release / Q000187:drug effects; D006967:Hypersensitivity / Q000188:drug therapy*; D007073:Immunoglobulin E / Q000502:physiology; D066298:In Vitro Techniques; D008168:Lung / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000187:drug effects; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000494:pharmacology; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D001562:Benzimidazoles; D006634:Histamine H1 Antagonists; D012701:Serotonin; D007073:Immunoglobulin E; D003189:p-Methoxy-N-methylphenethylamine; D006632:Histamine; C043345:emedastine