SYNTHETIC INHIBITORS OF TISSUE KALLIKREIN - EFFECTS IN-VIVO IN A MODEL OF ALLERGIC INFLAMMATION

We have recently developed synthetic low molecular weight inhibitors o f both tissue and plasma kallikreins. Several of these were evaluated in vivo in the ovalbumin-sensitised guinea pig for their ability to pr event the bronchoconstriction elicited by antigen challenge. The selec tive tissue kallikrein inhibitor CH-694 (but not the selective plasma kallikrein inhibitor CH-684) caused highly significant falls in airway s resistance when it was administered at 10 mg/kg intraperitoneally 15 min before and 90 min after challenge. There was also a highly signif icant fall in the tissue kallikrein activity measured in broncho-alveo lar lavage fluid. Inhibitors of tissue kallikrein may prove effective in the treatment of allergic inflammation in man.