Histamine liberation as a result of nonreceptor interaction.

The highly lipophilic drug exaprolol liberates histamine from isolated mast cells and decreases the uptake of extracellular histamine in a dose-dependent manner. Intracellular histamine depletion was confirmed by electron microscopy and was accompanied by calcium displacement from intracellular storage sites. The significant decrease in membrane fluidity due to exaprolol was temperature-dependent and was most probably a result of its high membrane affinity and intracellular penetration. Membrane perturbation by exaprolol may account for this nonreceptor interaction. This could contribute to the understanding of adverse reactions to beta-adrenoceptor blocking drugs.