Comparative effects of rilmenidine and clonidine on bronchial responses to histamine in asthmatic subjects.
1. The effects of pretreatment with clonidine and rilmenidine, a new alpha 2-adrenoceptor agonist, on the bronchial responses to inhaled histamine were studied on 3 different days in a controlled, double-blind, randomized study in 12 asymptomatic asthmatic subjects. Clonidine and rilmenidine were orally administered as single and equipotent doses of 150 micrograms and 1 mg, respectively. All the subjects were non-smokers with normal lung function tests (forced expiratory volume in one second (FEV1) = 97 +/- 10% predicted FEV1). 2. Histamine (first dose = 543 nmol) was delivered by a breath activated dosimeter (DeVilbiss no. 646 nebulizer) every 5 min; FEV1 was measured in triplicate after each dose and the largest value was analyse. The three dose-response curves were compared by analysis of variance. 3. Both clonidine and rilmenidine decreased arterial blood pressure in all subjects. There was no difference in baseline values and pre-challenge values of FEV1 after placebo, clonidine and rilmenidine on the 3 study days. Compared with placebo, both rilmenidine and clonidine significantly increased the bronchial responses to histamine (P less than 0.05 and P less than 0.01 respectively) an effect which was significantly more marked with clonidine than rilmenidine (P less than 0.05). 4. We suggest that the enhancement of bronchial responsiveness to histamine by clonidine and rilmenidine may result from their effects on both central and peripheral alpha 2-adrenoceptors, and that the lesser aggravation of histamine-induced bronchial obstruction in asthmatic subjects on rilmenidine might be explained by its lesser central and/or greater peripheral effects than clonidine.
Dinh Xuan
A T
AT
Laboratoire de Physiologie et d'Explorations Fonctionnelles Respiratoires, Hôpital Cochin, Paris, France.
Matran
R
R
Regnard
J
J
Vitou
P
P
Advenier
C
C
Lockhart
A
A
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000328:Adult; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001980:Bronchi / Q000187:drug effects / Q000503:physiopathology; D003000:Clonidine / Q000494:pharmacology*; D005260:Female; D005541:Forced Expiratory Volume; D006632:Histamine; D006801:Humans; D008297:Male; D010080:Oxazoles / Q000494:pharmacology*; D000077769:Rilmenidine
D000316:Adrenergic alpha-Agonists; D010080:Oxazoles; D006632:Histamine; D003000:Clonidine; D000077769:Rilmenidine