Influence of antihistamine (astemizole) and anticholinergic drugs (ipratropium bromide) on bronchoconstriction induced by substance P.
Several studies have demonstrated that neuropeptides are present in bronchial tissue. The aim of this study was to evaluate in vivo the influence of antihistamine in comparison to an anticholinergic drug on bronchospasm induced by inhalation of substance P (SP). Seven moderate asthmatic patients (mean age = 34.4 +/- 8.9), five being female, were studied. The acetate salt of SP was prepared in 0.9% saline to produce a dose range of 23 to 184 x 10(-6) mol. Patients were studied on three separate days with an interval of 3 weeks between challenges. On the first day the dose of SP producing a 20% change in FEV1 was calculated from the individual semilogarithmic dose-response curve. On subsequent days, in a randomized double-blind manner, the patients were treated either with astemizole (20 mg BID for three days) and placebo ipratropium bromide or with placebo of astemizole (twice a day for three days) and with pressurized aerosol of ipratropium bromide (IB) (40 micrograms 20 minutes before the challenge). Two way analysis of variance was used for statistical analysis. Our results demonstrated that inhaled SP is able to produce a dose-response curve of bronchoconstriction with a geometric mean of PD20 of 50.51 x 10(-6) moles (37.38 to 68.19 x 10(-6) mol). Treatment with astemizole induced a geometric mean PD20 of 65.51 x 10(-6) mol (33.02 to 130.21 x 10(-6) mol) and the premedication with the IB induced a significant (P less than .05) shift of dose-response curve to SP (geometric mean PD20 = 109.1 x 10(-6) mol; 58.67 to 204.05 x 10(-6) mol). Our results demonstrated that bronchoconstriction induced by SP could be attributed to a weak cholinergic activation and not to histamine release.
Institute of Respiratory Diseases, University of Catania, Italy.
N
N
Crimi
F
F
Palermo
R
R
Oliveri
B
B
Palermo
C
C
Vancheri
R
R
Polosa
A
A
Mistretta
D000280:Administration, Inhalation; D000328:Adult; D016589:Astemizole; D001286:Atropine Derivatives / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D001986:Bronchial Spasm / Q000139:chemically induced / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006634:Histamine H1 Antagonists / Q000627:therapeutic use*; D006801:Humans; D009241:Ipratropium / Q000627:therapeutic use*; D008297:Male; D013373:Substance P / Q000008:administration & dosage / Q000009:adverse effects*
D001286:Atropine Derivatives; D001562:Benzimidazoles; D006634:Histamine H1 Antagonists; D013373:Substance P; D016589:Astemizole; D009241:Ipratropium