Reversal of histamine-induced bronchoconstriction by the H1-receptor antagonist levocabastine: a potential model for efficacy in anaphylaxis.
1. The rate of onset and magnitude of the effect of levocabastine, a potent H1-receptor antagonist, in reversing histamine-induced bronchoconstriction were determined in a double-blind cross-over trial against saline placebo. Histamine was administered by nebuliser so that forced expiratory volume in 1 second (FEV1) was reduced to 80-75% of baseline FEV1 in 10 men with mildly or moderately responsive airways and the effects of intravenous injection of saline or saline + 200 micrograms levocabastine were studied. 2. The maximum rate of recovery of FEV1 was 7[2-10]% min-1 (median [range]) in the first 5 min after levocabastine injection, but only 4[1-7]% min-1 after saline alone (P less than 0.05). 3. The median area under the recovery curve of FEV1 from 0 to 30 min after injection was 405 [228-498]% basal FEV1 X min after levocabastine and 301[98-502]% basal FEV1 X min after saline alone (P less than 0.002). 4. FEV1 returned to 90% of baseline within 30 min in all subjects after levocabastine, but not after saline alone (P less than 0.002). 5. Histamine-induced bronchoconstriction was relieved more quickly by levocabastine than saline alone. This model may have application to the study of drugs used in the treatment of anaphylaxis.
Ferner
R E
RE
Wolfson Unit of Clinical Pharmacology, University of Newcastle upon Tyne.
Ward
C
C
Kelly
C
C
Connolly
M
M
Bateman
D N
DN
Rawlins
M D
MD
D000328:Adult; D000707:Anaphylaxis / Q000188:drug therapy*; D001986:Bronchial Spasm / Q000139:chemically induced / Q000188:drug therapy*; D004311:Double-Blind Method; D005541:Forced Expiratory Volume; D006632:Histamine; D006634:Histamine H1 Antagonists / Q000627:therapeutic use*; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000627:therapeutic use*; D011897:Random Allocation
D006634:Histamine H1 Antagonists; D010880:Piperidines; D006632:Histamine; C047340:levocabastine