Abstract

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.