Effect of 1-(2-ethoxyethyl)-2-(4-methyl-1-homopiperazinyl)-benzimida zole difumarate (KB-2413), a new antiallergic, on chemical mediators.
Effects of 1-(2-ethoxyethyl)-2-(4-methyl-1-homopiperazinyl)benzimidazol e difumarate (KB-2413) on chemical mediators were investigated in vitro and in vivo. Antihistaminic activity of KB-2413 in vitro was about 2, 7 and 5 times more potent than those of chlorpheniramine, diphenhydramine and clemastine, respectively, and equipotent to that of ketotifen. This antihistaminic activity of KB-2413 was competitive antagonism to histamine. In the study preventing histamine-induced mortality in guinea pigs, the antihistaminic potency of KB-2413 (p.o.) was about 39, 780, 68 and 3 times more potent than those of chlorpheniramine, diphenhydramine, clemastine and ketotifen, respectively. In the study preventing histamine-induced increase in vascular permeability, the antihistaminic potency of KB-2413 (p.o.) was about 27 and 4 times greater than those of chlorpheniramine and ketotifen, respectively. The preventing activity of KB-2413 (i.v.) on histamine-induced increase in airway resistance was about 10 and 2 times more potent than those of chlorpheniramine and ketotifen, respectively. These results indicate that the antihistaminic potency of KB-2413 is stronger than that of chlorpheniramine and that of ketotifen which has the strongest antihistaminic activity of all reference drugs. On the other hand, KB-2413 had only very weak anticholinergic, antibradykinin and antiserotonin activity in the study in vitro or in vivo, so that KB-2413 had selective antihistaminic activity. Therapeutic index of KB-2413 calculated from the antihistaminic potency on histamine-induced mortality and acute toxicity in guinea pigs was about 110 times greater than that of chlorpheniramine.(ABSTRACT TRUNCATED AT 250 WORDS)
D000109:Acetylcholine / Q000494:pharmacology; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001920:Bradykinin / Q000494:pharmacology; D002199:Capillary Permeability / Q000187:drug effects; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D007665:Ketotifen / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010276:Parasympatholytics / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects
D001562:Benzimidazoles; D006634:Histamine H1 Antagonists; D018377:Neurotransmitter Agents; D010276:Parasympatholytics; D012702:Serotonin Antagonists; D006632:Histamine; C043345:emedastine; D000109:Acetylcholine; D001920:Bradykinin; D007665:Ketotifen