Exaprolol

Abstract: The perturbation effect of the beta-adrenoceptor blocking drugs atenolol, propranolol, practolol, oxprenolol, doberol, pronethanol, metipranolol, alprenolol, Ko-1124, pindolol, and exaprolol on rat brain lipid membrane was investigated by ESR spectroscopy using the spin probe method. Using stearic acids spin labeled at the 5th, 12th, and 16th positions, it was found that lipophilic drugs disorder the membrane and their effect is about 5-10 times higher at the 16th carbon membrane depth than at the 5th depth. Exaprolol induced nonlamellar phases in the bovine brain lipid membrane as detected by 31P NMR spectroscopy. The relative potencies of the drugs at 10 mmol/liter concentration to disorder the lipid membrane at the 16th carbon depth were in the order: exaprolol greater than alprenolol approximately equal to propranolol greater than metipranolol approximately equal to doberol greater than control sample greater than pindolol approximately equal to practolol approximately equal to atenolol. This order qualitatively corresponds with some of their nonspecific biological membrane activities but is not related to their beta-adrenoceptor blocking potencies. The inequality of the membrane perturbation propensities of the drugs indicates that they perturb the lipid membrane in a structure-dependent manner, i.e., that each induces a specific rather than a nonspecific membrane perturbation.

Abstract: The beta-adrenoceptor blocking drug exaprolol liberated histamine from isolated rat mast cells in a dose- and time-dependent way. Histamine was liberated within seconds and was not followed by a parallel granule liberation. The inhibition of histamine liberation was induced with low temperature, low pH, high concentration of Ca2+, TTD, suramin and EDTA. Subcellular distribution of3H-exaprolol demonstrated a quantitative relationship between histamine depletion against exaprolol uptake in isolated rat mast cell granules. A nonspecific mechanism of action in the effect of exaprolol on mast cells is discussed. It is proposed that the drug acts on mast cells due to the direct and indirect ion exchange mechanism resulted in disproportion between histamine and granule liberation.

Abstract: Chloroquine liberated a relatively low amount of histamine from isolated rat mast cells. In a dose-dependent way, this drug inhibited histamine liberation from mast cells stimulated with compound 48/80, A23187, concanavalin A plus phosphatidylserine (Con A + PS) and abolished histamine liberation induced by exaprolol. The degranulation was decreased in cells stimulated with 48/80, Con A + PS and exaprolol. Chloroquine significantly inhibited the formation of thromboxane B2 in mast cells stimulated with 48/80, Con A + PS and A23187. We assume that chloroquine interferes with mast cells at a plasmic membrane site as well as intracellularly.