In vitro and in vivo activity profile of RHC 2851: a new orally effective antiallergic agent.

RHC 2851 has been investigated for its antiallergic activity in three in vitro and two in vivo models of anaphylaxis. We have also compared its activity profile in these models with that of disodium cromoglycate (DSCG), doxantrazole, ketotifen and oxatomide. RHC 2851, given i.p., was 6 times more potent than DSCG, and given orally it was 3 times more potent than doxantrazole. As an inhibitor of mediator release, the activity profile of RHC 2851 was identical to that of DSCG in the following respects: inhibition of IgE-mediated in vitro release of histamine from rat mast cells (RMC) but not human basophils (HuB), possession of tachyphylactic properties and demonstration of rapid loss of inhibitory activity as a function of time before antigen challenge as well as inability to inhibit IgG1-mediated release of histamine, both in vitro and in vivo, and lack of mediator antagonist activity. Ketotifen and oxatomide did not inhibit either IgE or IgG1-mediated release of histamine in vitro or in vivo, and were potent mediator antagonists in vivo. We conclude that RHC 2851 is an orally effective inhibitor of mediator release with a mechanism of action similar to that of DSCG and different from that of ketotifen and oxatomide.