Skip to main content
PMC home page
British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1988 Dec;26(6):703–708. doi: 10.1111/j.1365-2125.1988.tb05308.x

Comparative effects of rilmenidine and clonidine on bronchial responses to histamine in asthmatic subjects.

A T Dinh Xuan 1, R Matran 1, J Regnard 1, P Vitou 1, C Advenier 1, A Lockhart 1
PMCID: PMC1386584  PMID: 2907408

Abstract

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.

Full text

PDF
704

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Advenier C., Floch A., Mallard B. Bronchopulmonary effects of clonidine on the bronchomotor responses of the guinea-pig. Eur J Pharmacol. 1983 Apr 22;89(1-2):85–94. doi: 10.1016/0014-2999(83)90611-8. [DOI] [PubMed] [Google Scholar]
  2. Andersson R. G., Fügner A., Lindgren B. R., Muacevic G. Inhibitory effects of clonidine on bronchospasm induced in guinea-pigs by vagal stimulation or antigen challenge. Eur J Pharmacol. 1986 Apr 16;123(2):181–185. doi: 10.1016/0014-2999(86)90658-8. [DOI] [PubMed] [Google Scholar]
  3. Andersson R. G., Lindgren B. R., Colldahl H. Inhibitory effects of imidazolines on histamine liberation from human leukocytes and on tracheal smooth muscle tone. Acta Pharmacol Toxicol (Copenh) 1978 May;42(5):381–387. doi: 10.1111/j.1600-0773.1978.tb02221.x. [DOI] [PubMed] [Google Scholar]
  4. Barnes P. J., Skoogh B. E., Brown J. K., Nadel J. A. Activation of alpha-adrenergic response in tracheal smooth muscle: a postreceptor mechanism. J Appl Physiol Respir Environ Exerc Physiol. 1983 Jun;54(6):1469–1476. doi: 10.1152/jappl.1983.54.6.1469. [DOI] [PubMed] [Google Scholar]
  5. Boushey H. A., Holtzman M. J., Sheller J. R., Nadel J. A. Bronchial hyperreactivity. Am Rev Respir Dis. 1980 Feb;121(2):389–413. doi: 10.1164/arrd.1980.121.2.389. [DOI] [PubMed] [Google Scholar]
  6. Brown M. J. Sites of action of alpha 2 agonists and antagonists. Am J Cardiol. 1988 Feb 24;61(7):18D–21D. doi: 10.1016/0002-9149(88)90459-6. [DOI] [PubMed] [Google Scholar]
  7. Dinh Xuan A. T., Regnard J., Matran R., Mantrand P., Advenier C., Lockhart A. Effects of clonidine on bronchial responses to histamine in normal and asthmatic subjects. Eur Respir J. 1988 Apr;1(4):345–350. [PubMed] [Google Scholar]
  8. Fish J. E., Ankin M. G., Kelly J. F., Peterman V. I. Regulation of bronchomotor tone by lung inflation in asthmatic and nonasthmatic subjects. J Appl Physiol Respir Environ Exerc Physiol. 1981 May;50(5):1079–1086. doi: 10.1152/jappl.1981.50.5.1079. [DOI] [PubMed] [Google Scholar]
  9. Floch A., Advenier C. Interaction between clonidine and histamine on the guinea-pig isolated trachea. J Pharm Pharmacol. 1985 Dec;37(12):913–915. doi: 10.1111/j.2042-7158.1985.tb05001.x. [DOI] [PubMed] [Google Scholar]
  10. Genissel P., Bromet N., Fourtillan J. B., Mignot A., Albin H. Pharmacokinetics of rilmenidine in healthy subjects. Am J Cardiol. 1988 Feb 24;61(7):47D–53D. doi: 10.1016/0002-9149(88)90465-1. [DOI] [PubMed] [Google Scholar]
  11. Grundström N., Andersson R. G. Inhibition of the cholinergic neurotransmission in human airways via prejunctional alpha-2-adrenoceptors. Acta Physiol Scand. 1985 Nov;125(3):513–517. doi: 10.1111/j.1748-1716.1985.tb07749.x. [DOI] [PubMed] [Google Scholar]
  12. Grundström N., Andersson R. G., Wikberg J. E. Inhibition of the excitatory non-adrenergic, non-cholinergic neurotransmission in the guinea pig tracheo-bronchial tree mediated by alpha 2-adrenoceptors. Acta Pharmacol Toxicol (Copenh) 1984 Jan;54(1):8–14. doi: 10.1111/j.1600-0773.1984.tb01889.x. [DOI] [PubMed] [Google Scholar]
  13. Grundström N., Andersson R. G., Wikberg J. E. Prejunctional alpha 2 adrenoceptors inhibit contraction of tracheal smooth muscle by inhibiting cholinergic neurotransmission. Life Sci. 1981 Jun 29;28(26):2981–2986. doi: 10.1016/0024-3205(81)90275-7. [DOI] [PubMed] [Google Scholar]
  14. Holtzman M. J., Sheller J. R., Dimeo M., Nadel J. A., Boushey H. A. Effect of ganglionic blockade on bronchial reactivity in atopic subjects. Am Rev Respir Dis. 1980 Jul;122(1):17–25. doi: 10.1164/arrd.1980.122.1.17. [DOI] [PubMed] [Google Scholar]
  15. Laubie M., Poignant J. C., Scuvée-Moreau J., Dabire H., Dresse A., Schmitt H. Pharmacological properties of (N-dicyclopropylmethyl) amino-2-oxazoline (S 3341), an alpha-2 adrenoceptor agonist. J Pharmacol. 1985 Jul-Sep;16(3):259–278. [PubMed] [Google Scholar]
  16. Lindgren B. R., Ekström T., Andersson R. G. The effect of inhaled clonidine in patients with asthma. Am Rev Respir Dis. 1986 Aug;134(2):266–269. doi: 10.1164/arrd.1986.134.2.266. [DOI] [PubMed] [Google Scholar]
  17. Lindgren B. R. New aspects on the treatment of inflammatory reactions and broncho-obstruction in bronchial asthma. Eur J Respir Dis Suppl. 1987;148:1–72. [PubMed] [Google Scholar]
  18. Macquin-Mavier I., Clerici C., Harf A. Effects of rilmenidine on bronchomotor responses in the guinea pig. Am J Cardiol. 1988 Feb 24;61(7):45D–46D. doi: 10.1016/0002-9149(88)90464-x. [DOI] [PubMed] [Google Scholar]
  19. Nadel J. A., Barnes P. J. Autonomic regulation of the airways. Annu Rev Med. 1984;35:451–467. doi: 10.1146/annurev.me.35.020184.002315. [DOI] [PubMed] [Google Scholar]
  20. Van Zwieten P. A. Pharmacology of the alpha 2-adrenoceptor agonist rilmenidine. Am J Cardiol. 1988 Feb 24;61(7):6D–14D. doi: 10.1016/0002-9149(88)90457-2. [DOI] [PubMed] [Google Scholar]
  21. Verbeuren T. J., Jordaens F. H., Zonnekeyn L. L., Herman A. G. Effect of the amino-oxazoline derivative S-3341 on pre- and postjunctional alpha-adrenoceptors in isolated blood vessels. Arch Int Pharmacodyn Ther. 1986 Nov;284(1):38–52. [PubMed] [Google Scholar]
  22. van Zwieten P. A., Thoolen M. J., Jonkman F. A., Wilffert B., de Jonge A., Timmermans P. B. Central and peripheral effects of S 3341 [(N-dicyclopropylmethyl)-amino-2-oxazoline] in animal models. Arch Int Pharmacodyn Ther. 1986 Jan;279(1):130–149. [PubMed] [Google Scholar]

Articles from British Journal of Clinical Pharmacology are provided here courtesy of British Pharmacological Society

RESOURCES