PHARMACOLOGIC CHARACTERIZATION OF THE ANTI-ALLERGIC ACTIVITY OF SK AND F-78729-A

  • 1 January 1978
    • journal article
    • research article
    • Vol. 207  (3) , 756-766
Abstract
SK&F 78729-A [5-acetyl-4-hydroxy-3-[1-[(3-amino-4-hydroxyphenyl)amino]ethylidene]-2H-pyran-2,6(3H)-dione hydrochloride], 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./oral, inhibited the antigen-induced rat 48-h 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. 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. Clinically, SK&F 78729-A apparently should exhibit a pharmacologic profile consistent with that of a prophylactic antiallergic agent.