Pharmacologic characterization of the antiallergic activity of SK&F 78729-A.
SK&F 78729-A, one of a series of pyranenamine compounds, was studied in several laboratory models of immediate-type hypersensitivity reactions. In vivo, SK&F 78729-A, i.v./p.o., inhibited the antigen-induced rat 48-hr passive cutaneous anaphylaxis by a mechanism other than end-organ antagonism to either histamine or serotonin. In vitro, the compound produced a concentration-related inhibition of the immunologic release of histamine and slow-reacting substance of anaphylaxis from passively sensitized fragmented rhesus monkey and canine lung, and modest inhibition of histamine release from passively sensitized fragmented rhesus monkey skin. Similarly, SK&F 78729-A inhibited the antigen-induced release of histamine from passively sensitized fragmented rat lung. Under certain conditions, SK&F 78729-A inhibited antigen-induced pathophysiologic pulmonary responses in in vivo canine and rhesus monkey models of allergic asthma. The results of these studies suggest that clinically, SK&F 78729-A should exhibit a pharmacologic profile consistent with that of a prophylactic antiallergic agent.
D000627:Aminophenols / Q000494:pharmacology*; D000818:Animals; D001200:Ascaris / Q000276:immunology; D001249:Asthma / Q000188:drug therapy / Q000209:etiology; D004285:Dogs; D000882:Haplorhini; D006636:Histamine Release / Q000187:drug effects; D006969:Hypersensitivity, Immediate / Q000150:complications / Q000188:drug therapy*; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects / Q000276:immunology; D008253:Macaca mulatta; D008297:Male; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects; D011714:Pyrans / Q000494:pharmacology*; D011753:Pyrones / Q000494:pharmacology*; D051381:Rats; D013189:SRS-A / Q000378:metabolism; D012867:Skin / Q000187:drug effects / Q000276:immunology
D000627:Aminophenols; D011714:Pyrans; D011753:Pyrones; D013189:SRS-A