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Following intraperitoneal sensitisation of rats with rat serum containing reaginic antibody, intravenous injection of blue dye and intraperitoneal challenge with antigen caused a release of histamine, slow-reacting substance of anaphylaxis (SRS-A) and dye into their peritoneal fluids. The times taken to reach peak concentrations after challenge were less than 2 min for histamine and between 5 and 10 min for SRS-A, whilst concentrations of dye were still increasing after 2½ h. The amounts of histamine released by antigen were sufficient to account for about 60% of this extravasation of dye. Disodium cromoglycate (DSCG) and a nitroindanedione (BRL 10833) inhibited extravasation by inhibition of mediator release. BRL 10833, unlike DSCG, was active after oral administration, and for a given inhibition of histamine release it produced a greater effect on extravasation when given orally than when injected intraperitoneally.

Four compounds with H₁ anti-histamine activity and four adrenoceptor stimulants, each given to rats prior to passive peritoneal anaphylaxis (PPA), inhibited extravasation of serum proteins into the peritoneal fluid at doses which had no effect on histamine release. In contrast, aminophylline and some non-steroidal anti-inflammatory agents inhibited extravasation only at doses which inhibited histamine release; they showed a similar type of activity to that of disodium cromoglycate (DSCG) and a nitroindanedione (BRL 10833), although they were much less potent. Predosing with DSCG reduced the potency of subsequent doses of DSCG, BRL 10833 and indomethacin, but not of aminophylline or phenylbutazone, and therefore DSCG, BRL 10833 and indomethacin may share a common pathway to produce activity. In the rat PPA system, no evidence was found for histamine ‘feedback’ inhibition of histamine release.

Passive peritoneal anaphylaxis in rats, sensitised with mouse antiserum, had characteristics of an IgE-mediated reaction, in that the serum was heat-labile and pretreatment of the rats with disodium cromoglycate (DSCG), or sodium nivimedone, inhibited the release of both histamine and slow-reacting substance of anaphylaxis (SRS-A). Sodium nivimedone was more potent than DSCG as an inhibitor of histamine release. Peak concentrations of histamine and SRS-A in the peritoneal fluids of the rats, were reached within 2 min of antigen challenge and fell to control levels after 20–30 min.

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