Agents and Actions

, Volume 13, Issue 1, pp 16–20 | Cite as

Histamine receptor blocking effects of cimetidine in the airways

  • V. Hartmann
  • H. Magnussen
  • W. OliverJr
  • W. M. Abraham
  • A. Wanner
  • T. Ahmed
Histamine and Kinins


We investigated the modification of histamine-induced bronchoconstriction by the H2-antagonist cimetidine in conscious sheep. One hundred breaths of 5% histamine aerosol increased mean (SD) pulmonary resistance (RL) by 5.6 (1.4) cmH2O/1/sec. This increase inRL was completely blocked by intravenous clemastine (0.5 mg), a specific H1-antagonist, indicating that the histamine-induced bronchoconstriction was mediated by H1-receptors. Intravenous cimetidine caused a dose-dependent enhancement of the histamine response between 1 and 1000 mg with a mean peak ΔRL of 15.3 (5) cmH2O/1/sec (P<0.05) at the 1000 mg dose, while it blocked the histamine response at a dose of 2400 mg [ΔRL=1.9 (2) cmH2O/1/sec,p=NS]. This paradoxic effect was not related to an anticholinergic mechanism as intravenous cimetidine (2400 mg) failed to block carbachol-induced (25 breaths of 1% solution) bronchoconstriction. We conclude that in the ovine airway, cimetidine is a selective H2-histamine receptor blocker at lower tissue concentrations, and a combined H2- and H1-histamine receptor blocker at high tissue concentrations.


Histamine Cimetidine Receptor Blocker Tissue Concentration Blocking Effect 


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  1. [1]
    P. Eyre andN. Chand, Histamine receptor mechanisms of the lung. InPharmacology of Histamine Receptors (Ed.C.R. Ganellin andE.M. Parsons), Bristol, UK 1981 (in press).Google Scholar
  2. [2]
    P. Eyre, Pulmonary histamine H1 and H2 receptor studies. InAsthma: Physiology, Immunopharmacology and Treatment, pp. 169–180 (Ed.L.M. Lichtenstein andK.F. Austen). Academic Press, New York 1977.Google Scholar
  3. [3]
    A.S.F. Ash andH.O. Schild,Receptors mediating some actions of histamine, Br. J. Pharmac.27, 427–439 (1966).Google Scholar
  4. [4]
    J.W. Black, W.A.M. Duncan, C.J. Durant, C.R. Ganellin andE.M. Parsons,Definition and antagonism of histamine H 2-receptors, Nature236, 385–390 (1972).CrossRefPubMedGoogle Scholar
  5. [5]
    R.W. Brimblecome, W.A.M. Duncan, G.J. Durant, J.C. Emmet, C.R. Ganellin andE.M. Parsons,Cimetidine — A non-thiourea, H 2-receptor antagonist, J. int. med. Res.3, 86–92 (1975).Google Scholar
  6. [6]
    J.M. Drazen, C.S. Venugopalan andN.A. Soter,H 2-receptor mediated inhibition of immediate type hypersensitivity reactions in vivo, Am. Rev. resp. Dis.117, 479–484 (1978).PubMedGoogle Scholar
  7. [7]
    J.R. Snapper, P.S. Braasch, R.H. Ingram Jr, S.H. Loring andJ.M. Drazen, In vivoeffect of cimetidine on canine pulmonary responsiveness to aerosol histamine, J. Allergy clin. Immun.66, 70–74 (1980).CrossRefPubMedGoogle Scholar
  8. [8]
    J.G. Maconochie, E.P. Woodings andD.A. Richards,Effects of H 1 and H 2 receptor blocking agents in non-asthmatic subjects, Br. J. clin. Pharmac.7, 231–236 (1979).Google Scholar
  9. [9]
    N.M. Eiser, P.D. Snashall, K.D. McRae, J. Mills andA. Guz A.,Bronchial histamine receptors in normal atopic, and asthmatic subject, Clin. Sci.58, 537–544 (1980).PubMedGoogle Scholar
  10. [10]
    R.A. Nathan, N. Segall, G.C. Glover andA.L. Shocket,The effects of H 1 and H 2 antihistamines on histamine inhalation challenges in asthmatic patients, Am. Rev. resp. Dis.120, 1252–1258 (1979).Google Scholar
  11. [11]
    R.A. Nathan, N. Segall andA.L. Shocket,A comparison of the actions of H 1 and H 2 antihistamines on histamine induced bronchoconstriction and cutaneous wheal reasponse in asthmatic patients, J. Allergy clin. Immuno.67, 171–177 (1981).CrossRefGoogle Scholar
  12. [12]
    T. Ahmed, P. Eyre, A.J. Januszkiewicz andA. Wanner,Role of H 1 and H 2 receptors in airway reactions to histamine in conscious sheep, J. appl. Physiol.49, 826–833 (1980).PubMedGoogle Scholar
  13. [13]
    J. Milic-Emilic, J. Mead, J.M. Turner andE.M. Glauser,Improved technique for estimating pleural pressure from esophageal balloon, J. appl. Physiol.19, 207–211 (1964).Google Scholar
  14. [14]
    P. Eyre,The pharmacology of sheep tracheobronchial muscle. A relaxant effect of histamine on the isolated bronchi, Br. J. Pharmac.36, 409–417 (1969).Google Scholar
  15. [15]
    P. Eyre,Histamine H 2-receptors in the sheep bronchus and cat trachea. The action of burimamide, Br. J. Pharmac.48, 321–323 (1973).Google Scholar
  16. [16]
    M. Dixon, D.M. Jackson andJ.M. Richards,The effects of H 1 and H 2 receptor agonists on total lung resistance, dynamic compliance and irritant receptor discharge in the compliance and irritant receptor discharge in the anesthetized dogs, Br. J. Pharmac.66, 203–209 (1979).Google Scholar
  17. [17]
    V. Hartmann, H. Magnussen, J.P. Holle andE. Schuler,Modulation of histamine induced bronchoconstriction with inhaled, oral and intravenous clemastine in normals and asthmatics, Thorax (in press).Google Scholar

Copyright information

© Birkhäuser Verlag 1983

Authors and Affiliations

  • V. Hartmann
    • 2
  • H. Magnussen
    • 2
  • W. OliverJr
    • 1
  • W. M. Abraham
    • 1
  • A. Wanner
    • 1
  • T. Ahmed
    • 1
  1. 1.Division of Pulmonary DiseaseMount Sinai Medical CenterMiami BeachUSA
  2. 2.Medizinische Universitäts-PoliklinikBonnWest Germany

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