Effects of H2-antihistamines in murine models of immediate hypersensitivity and chronic inflammation.
Effects of H2-antihistamines alone and in combination with H1-antihistamines on immediate hypersensitivity and chronic inflammation in mice and rats were investigated. The mouse PCA reaction was inhibited partially by a minimum effective dose of diphenhydramine and blocked completely when administered simultaneously with either famotidine, ranitidine or cimetidine. There was similar synergism between H1- and H2-antihistamines in inhibiting the PCA-like reaction in rat paw. Famotidine alone was able to inhibit those two reactions in a large oral dose of 100 mg/kg. A five-day course of therapy with H2-antihistamines alone or in combination with pyrilamine, suppressed effectively the chronic swelling induced in the hind paw of BUF rats. From these results, it is deduced that simultaneous blockage of both histamine H1- and H2-receptors may be necessary for sufficient inhibition of the microvascular permeability increase in some kinds of anaphylactic reactions, and that histamine, mainly interacting with H2-receptors, may take an important role for activation of a certain phase of chronic inflammation where bone destruction, blood capillary growth and mast cell degranulation involve.
Kaneta
S
S
Department of Toxicology, Hokkaido Institute of Pharmaceutical Sciences, Otaru, Japan.
Yanaguimoto
H
H
Kagaya
J
J
Ishizuki
S
S
Fujihira
E
E
D000818:Animals; D001169:Arthritis, Experimental / Q000473:pathology / Q000517:prevention & control*; D002199:Capillary Permeability / Q000187:drug effects; D002908:Chronic Disease; D004195:Disease Models, Animal; D004338:Drug Combinations; D004357:Drug Synergism; D005260:Female; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D006969:Hypersensitivity, Immediate / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008813:Mice, Inbred ICR; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011968:Receptors, Histamine / Q000187:drug effects
D004338:Drug Combinations; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D011968:Receptors, Histamine