Effect of an inhaled histamine H3-receptor agonist on airway responses to sodium metabisulphite in asthma.
Histamine H3-receptor agonists inhibit excitatory neuro-transmission in human and guinea-pig airways. Since neural bronchoconstriction may be important in asthma we have studied the effect of a specific H3-receptor agonist R-alpha-methylhistamine (alpha MeHA) on bronchoconstriction induced by the inhaled irritant sodium metabisulphite (MBS) in six mild asthmatic subjects in a randomised double-blind crossover study. Subjects received either alpha MeHA, 10 mg (as a chloride salt) or matched placebo (P) and were then challenged with doubling concentrations of MBS (0.3-80 mg ml-1) nebulised from a dosimeter at 5 min intervals with measurement of specific airway conductance (sGaw) and FEV1 at 2 and 4 min respectively after each inhalation. There was no effect of alpha MeHA on baseline airway calibre and the log concentrations of MBS required to lower sGaw by 50% (log PC50) and FEV1 by 20% (log PC20) were not significantly different after alpha MeHA when compared with placebo, suggesting that selective stimulation of airway H3-receptors does not inhibit MBS-induced bronchoconstriction.
O'Connor
B J
BJ
Department of Thoracic Medicine, National Heart and Lung Institute, Royal Brompton Hospital, London.
Lecomte
J M
JM
Barnes
P J
PJ
D000280:Administration, Inhalation; D000328:Adult; D001249:Asthma / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects*; D017442:Histamine Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008761:Methylhistamines / Q000008:administration & dosage / Q000494:pharmacology*; D008875:Middle Aged; D011968:Receptors, Histamine / Q000187:drug effects*; D013447:Sulfites
D017442:Histamine Agonists; D008761:Methylhistamines; D011968:Receptors, Histamine; D013447:Sulfites; C005200:sodium metabisulfite; C069357:alpha-methylhistamine