Inhaled antihistamines--bronchodilatation and effects on histamine- and methacholine-induced bronchoconstriction.

Abstract

Nogrady, S G, and Bevan, C (1978). Thorax, 33,[700][701][702][703][704]. Inhaled antihistaminesbronchodilatation and effects on histamine-and methacholine-induced bronchoconstriction. To assess further the bronchodilator activity of inhaled antihistamines ten stable asthmatic subjects inhaled aerosols of clemastine, 1 mg/ml, and saline placebo administered double blind. Subjects underwent bronchial challenge with increasing concentrations of histamine and methacholine, and specific airways conductance was measured by whole body plethysmography at each concentration. There was a significant 21-9% increase in specific airways conductance after inhalation of clemastine. Subjects could tolerate significantly higher mean concentrations of histamine when treated with clemastine than with saline. The shift of the cumulative log histamine dose-response curve suggests that such protection is due to competitive antagonism to the inhaled clemastine. Clemastine did not protect subjects against methacholine-induced bronchoconstriction, which suggests that its bronchodilator properties are not related to any anticholinergic action.

Histamine and allergen induced changes in nasal airways resistance measured by anterior rhinomanometry: reproducibility of the technique and the effect of topically administered antihistaminic and anti‐ allergic drugs.

“…SCG was administered in a concentration of 20 mg ml-', the concentration used in clinical practice for the treatment of allergic rhinitis. The concentration of clemastine 1 mg ml-1 was chosen as this had previously been shown to inhibit the bronchial response to inhaled histamine (Nogrady & Bevan, 1978). We have previously shown in studies in human skin that ketotifen was twice as potent as clemastine, and we therefore chose to administer ketotifen at a dose theoretically equipotent to clemastine, namely 0.5 mg ml-'.…”

Use of Anterior Rhinometry in Nasal Provocation Challenges with Allergen and Evaluation of the Effects of Ketotifen, Clemastine and Sodium Cromoglycate on these Responses

“…Sodium cromoglycate was given in a concentration of 20 «g/'ml which is the concentration used in clinical practice for the treatment of rhinitis. Clemastine was given in a concentration of 1 mg/ml as this concentration has been shown to inhibit successfully the bronchial response to histamine provocation [9], Ketotifen was administered at 0.5 mg/ml. This concentration was considered to represent a reasonable topical dose in relation to the oral dose of 1 mg used in clinical practice.…”

“…Sodium cromoglycate is thought to have mast cell stabilizing properties [5,10] although actions on receptors in bronchial smooth muscle have also been postulated [3]. Clemastine is an antihistamine with very weak anticholinergic properties [9]. Ketotifen is a new drug belonging to the group of benzocycloheptathiophenes and thought to have both antihistaminic and other anti-allergic properties, including ac tions as a mast cell stabiliser and a phos phodiesterase inhibitor [6].…”

H2‐receptor blockade and exercise‐induced asthma.

“…Histamine1 receptor (Hj) blockade causes bronchodilatation (Popa, 1977) and protects against both histamine (Nogrady & Bevan, 1978) and exercise induced bronchoconstriction (Hartley & Nogrady, 1980). Bronchodilating H2-receptors have been suggested by observations that bronchial muscle, pretreated with HI-receptor antagonists, relaxes further with the addition of histamine (Dunlop & Smith, 1977).…”