Rats actively sensitised to bovine serum albumin (BSA) in Freund’s complete adjuvant were challenged by intraperitoneal injection of BSA. By washing out the peritoneal cavities at different times it was possible to divide the changes that occurred into two phases. The first was characterised by the release of histamine and slow reacting substance of anaphylaxis (SRS-A) with an associated extravasation of plasma proteins. The second phase was characterised by an increase in neutrophilic polymorphonuclear cells in the peritoneal cavity. Extracellular enzyme activities were also investigated. The kinetics of these events were studied and are discussed in terms of the possible mechanisms involved.

BRL 22321, a compound that has mast cell stabilizing activity similar to that of disodium eromoglyeate and in addition has smooth muscle relaxing activity BARBARA AbstractBRL 22321 is 4,9-dlhydro-6,7-dimethyl-4,9-dioxo-lHnaphtho[2,3-dl-v-triazole sodium salt. It combines some of the chemical structural features of disodium cromoglycate (DSCG) and theophylline. It has mast cell stabilizing activity similar to that of DSCG and in addition it has some smooth muscle relaxant activity. BRL 22321 was more potent than DSCG as an inhibitor of rat passive cutaneous and peritoneal anaphylaxis (PCA and PPA) and histamine release by antigen from passively sensitized rat peritoneal cells In vitro. In the rat PCA test it was active when given orally and a large intravenous dose of DSCG reduced the potency of subsequent intravenous doses of either DSCG or BRL 22321, suggesting that the compounds were active by a common pathway. The compounds had similar potencies as inhibitors of the release, by antigen, of histamine and slow reacting substance of anaphylaxis (SRS-A) from passively sensitized human lung fragments. BRL 22321 was more potent than DSCG and theophylline as an inhibitor of a cyclic adenosine and a cyclic guanosine monophosphate phosphodiesterase. BRL 22321 inhibited histamine release in systems in which DSCG was inactive, for example it inhibited histamine release by antigen from chopped lung taken from hyperlmmune guinea pigs and by antLIgE from human leucocytes; in these tests it was more potent than theophylline. BRL 22321 had smooth muscle relaxant activity not shown by DSCG. It relaxed histamine elevated tone in guinea pig lung strip and tracheal spiral preparations at doses at which theophylllne produced a dose dependent response. It was difficult to compare potencies since there was a difference in the nature of the responses to the drugs. DSCG had little activity over the same dose range or at higher doses. BRL 22321 also reduced increased airways resistance in the anaesthetized guinea pig produced by 5-hydroxytryptamlne (5-HT) or histamine but at somewhat higher doses than those at which theophylline was active. BRL 22321 was not an antagonist of acetylcholine, histamine, 5 HT or SRS-A on the isolated guinea pig ileum.