Inhibition of mast cell degranulation-induced drop of blood pressure with clemastine, cromolyn and compound 48/80 pretreatment

Abstract

Many basic compounds, including numerous drugs, can release histamine and other infl ammatory mediators from mast cells [1]. Drug-induced degranulation of mast cells is an undesired effect and therefore should be avoided. One of the consequences of drug-induced mast cell degranulation is a drop of the mean arterial blood pressure (MAP) [2]. Prevention of the drop of MAP with specifi c agents, targeting either the action of released mediators from mast cells or the extent of mast cell degranulation, is a reasonable approach to clarify the mechanism of this undesired effect. In this study we evaluated three in vivo models using this approach. In all three models compound 48/80 was used as a tool to mimic the undesired mast cell degranulation effect of potential new drugs and the drop of MAP was measured following its application. In the fi rst two models inhibition of the drop of MAP with the selective H1 antagonist clemastine and with the mast cell stabilizer cromolyn was determined respectively. In the third model the drop of MAP was studied in mast cell depleted rats.