1. Evaluation of calcium entry blockers in several models of immediate hypersensitivity.
- Author
-
Ritchie DM, Sierchio JN, Bishop CM, Hedli CC, Levinson SL, and Capetola RJ
- Subjects
- Animals, Arachidonate Lipoxygenases, Arachidonic Acids biosynthesis, Bronchial Spasm chemically induced, Cinnarizine analogs & derivatives, Cinnarizine pharmacology, Diltiazem pharmacology, Flunarizine, Guinea Pigs, Histamine Release drug effects, Lipoxygenase metabolism, Male, Mast Cells drug effects, Nifedipine pharmacology, Rats, Verapamil pharmacology, Calcium Channel Blockers pharmacology, Hydroxyeicosatetraenoic Acids, Hypersensitivity, Immediate
- Abstract
Several calcium-entry blockers, i.e., verapamil, nifedipine, flunarizine and diltiazem, were evaluated for their effects in models of immediate hypersensitivity disease. Verapamil, flunarizine and diltiazem were all effective in inhibiting antigen-induced bronchospasm in the guinea pig; however, the effects seen were at relatively high doses compared to the doses known to cause cardiovascular effects. Nifedipine caused no significant inhibition of resistance or compliance changes induced by antigen. Flunarizine, verapamil and diltiazem were ineffective in inhibiting antigen-induced histamine release from rat peritoneal mast cells in vitro. Although these compounds were active inhibitors of 5-D-[5,6,8,9,H,12,14,15-3H(N)]-hydroxy-6,8,11,14-eicosatetraenoic acid production in rat basophilic leukemia-1 cells, only flunarizine and verapamil showed effects on the 5-lipoxygenase enzyme when assayed directly. Also, these compounds were ineffective on SRS-A mediated bronchospasm in vivo. These data suggest that the currently available calcium entry blockers have little potential use in immediate hypersensitivity reactions.
- Published
- 1984