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, 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

Abstract

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.

Keywords

Histamine Cimetidine Receptor Blocker Tissue Concentration Blocking Effect 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  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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