Comparison of effects of investigational compounds upon allergic phenomena in rodents in vivo and in human basophils in vitro.
Investigational compounds active in anti-allergic/anti-asthmatic screens in rodents in vivo (IgE-mediated passive cutaneous anaphylaxis in rats, IgE-mediated anaphylactic bronchoconstriction in guinea pigs, and histamine-, or acetylcholine-induced bronchoconstriction in guinea pigs) were examined for their effects against IgE-mediated histamine release from human basophiles. Fifty-seven% (19/33) of investigational compounds active against passive cutaneous anaphylaxis in rats and 40% (12/30) of compounds active against anaphylactic bronchoconstriction in guinea pigs were active also against histamine release from human basophiles. Twenty-eight percent (8/29) and 38% (6/15) of compounds active agonist histamine- and acetylcholine-bronchoconstriction in guinea pigs, respectively, were active also against histamine release from human basophiles. The lack of consistent activity of investigational compounds in the in vivo IgE-mediated anaphylactic screens suggests that diverse inhibitory mechanisms are involved. Anaphylactic histamine release from human basophiles may serve as an adjunct in the determination of the activity profiles of new antiallergic agents. It is of limited value in the search for new bronchodilators.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001249:Asthma / Q000503:physiopathology; D001491:Basophils / Q000187:drug effects*; D001980:Bronchi / Q000187:drug effects; D001993:Bronchodilator Agents; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy* / Q000503:physiopathology; D007073:Immunoglobulin E / Q000502:physiology; D066298:In Vitro Techniques; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects; D051381:Rats
D001993:Bronchodilator Agents; D007073:Immunoglobulin E; D006632:Histamine; D000109:Acetylcholine