Skip to main content
Log in

Cardiac and vascular effects of elliptinium in guinea pigs. Involvement of a histaminergic mechanism

  • Histamine and Kinins
  • Published:
Agents and Actions Aims and scope Submit manuscript

Abstract

This work reports a study of the effects of elliptinium on heart rate, arterial blood pressure and capillary permeability in guinea-pigs. The variations in capillary permeability are determined by spectrophotometric assay of skin Evans blue. Elliptinium induces dose-independent tachycardia and dose-related hypotension. For the highest dose (6 mg/kg), elliptinium induces lethal collapsus. Elliptinium increases capillary permeability and this effect, particularly marked at 1 mg, i.d., is partially antagonized by mepyramine-cimetidine association. These results are discussed in comparison with those obtained with elliptinium on other parameters, with histamine and with different antitumoral agents. The increase in capillary permeability raises the question of its relevance to the anticancer activity of elliptinium.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. J.B. Le Pecq, C. Gosse, Dat-Xuong andC. Paoletti,Deux nouveaux dérivés anti-tumoraux: l'hydroxy-9-méthyl-2-ellipticinium (acetate) et l'hydroxy-9-diméthyl-2, ellipticinium (chlorure). Action sur la leucémie L-1210 de la souris, C. R. Acad. Sci.281, 1365–1367 (1975).

    Google Scholar 

  2. P. Juret, A. Tanguy, A. Girard, J.Y. Le Talaer, J.S. Abbatucci, Dat-Xuong, J.B. Le Pecq andC. Paoletti,Preliminary trial of 9-hydroxy-2-methyl-ellipticinium (NCS 264-137) in advanced human cancers, Eur. J. Cancer15, 205–206 (1978).

    Google Scholar 

  3. A. Eschalier, Dat-Xuong andJ. Lavarenne,Effets bronchiques de l'acétate d'hydroxy-9-méthyl-2-ellipticinium, comparaison avec l'histamine, J. Pharmac. (Paris)11, 43–55 (1980).

    Google Scholar 

  4. J. Lavarenne, A. Eschalier, C. Burtin, G. Dureng, B. Lebel andC. Advenier,Extra-antitumoral properties of 9-hydroxy-2-methyl-ellipticinium. A possible link with histamine release, Eighth International Congress of Pharmacology, Abstracts, p. 707 (1981).

  5. A. Eschalier, G. Dureng, H. Chevalier andJ. Lavarenne,Effets de l'acétate d'hydroxy-9-méthyl-2-ellipticinium (OH-9-CH 3-2-E) sur la sécrétion gastrique du rat, J. Pharmac. (Paris)11, 316–317 (1980).

    Google Scholar 

  6. A. Eschalier, C. Advenier, B. Lebel, C. Burtin andJ. Lavarenne,Histamine-releasing properties of hydroxy-9-methyl-2-ellipticinium acetate, Cancer Chemotherapy Pharmacology5, 233–236 (1981).

    Article  Google Scholar 

  7. P. Juret, A. Tanguy, A. Girard, J.Y. Letalaer, J.S. Abbatucci, Dat-Xuong, J.B. Le Pecq andC. Paoletti,L'acétate d'hydroxy-9-méthyl-2-ellipticinium (NSC 264-137). Etude toxicologique et thérapeutique chez 100 cancéreux, Nouv. Presse Med.8, 1495–1498 (1979).

    PubMed  Google Scholar 

  8. J. Rouesse, T. Tursz, T. Le Chevalier, D. Huertas, J.L. Amiel, G. Brule, B. Callet, J.P. Droz, P.M. Voisine, M. Sancho-Garnier, J.B. Le Pecq andC. Paoletti,Intérêt de la 2-N-méthyl-9-hydroxyellipticine (NSC 264-137) dans le traitement des cancers métastasés, Nouv. Presse Med.10, 1997–1999 (1981).

    PubMed  Google Scholar 

  9. M. Mordelet-Dambrine, F. Dubois andJ.L. Parrot,Mesure de la perméabilité capillaire au cours de la libération d'histamine. Effet du cromoglycate disodique, Thérapie29, 851–862 (1974).

    Google Scholar 

  10. A.A. Miles andE.M. Miles,Vascular reactions to histamine, histamine-liberator and leukotaxine in the skin of guinea-pigs, J. Physiol., Lond.118, 228–257 (1952).

    Google Scholar 

  11. S. Wallenstein, C.L. Zucker andJ.L. Fleiss,Some statistical methods useful in circulation research, Circulation Res.47, 1–9 (1980).

    PubMed  Google Scholar 

  12. R.W. Brimblecombe, D.A.A. Owen andM.E. Parsons,The cardiovascular effects of histamine in laboratory animals, Agents and Actions4, 191–192 (1974).

    PubMed  Google Scholar 

  13. H.H. Dale andP.P. Laidlaw,The physiological action of betaiminazolylethylamine, J. Physiol., Lond.41, 318–344 (1910).

    Google Scholar 

  14. J.H. Burn andH.H. Dale,The vasodilator action of histamine and its physiological significance, J. Physiol., Lond.61, 185–214 (1926).

    Google Scholar 

  15. D.B. Beleslin,Factors influencing the secondary use of blood pressure produced by histamine in the rats, Archs int. Pharmacodyn. Thér.138, 32–40 (1962).

    Google Scholar 

  16. E.R. Loew,Pharmacology of antihistamine compounds, Physiol. Rev.27, 542–573 (1947).

    Google Scholar 

  17. W.G. Spector andD.A. Willoughby,The antagonism of substances that increase vascular permeability in the rat, J. Path.86, 487–496 (1963).

    Article  Google Scholar 

  18. M.K. Church andP. Miller,Simple models of anaphylaxis and of histamine and 5-hydroxytryptamine-induced inflammation using the mouse pinna, Br. J. Pharmac.55, 315 (1975).

    Google Scholar 

  19. W. Lorenz, M. Thermann, H. Hamelmann, A. Schmal, D. Maroske, H.J. Reimann, J. Kusche, F. Schingale, P. Dermann andP. Keck, Influence of H1-and H2-receptors antagonists on the effects of histamine in the circulatory system and on plasma histamine levels.Int. Symposium on Histamine H 2-Receptor Antagonists, pp. 151–168. (EdsJ. Clive Wood andM.A. Simkins). Deltakos (UK) Ltd., London, W1 (1973).

    Google Scholar 

  20. R.W. Brimblecombe, W.A.M. Duncan, D.A.A. Owen andM.E. Parsons,The pharmacology of burinamide and metiamide, two histamine H 2-receptor antagonists, Fed. Proc. Fedn Am. Socs exp. Biol.35, 1931–1935 (1976).

    Google Scholar 

  21. F. Joo, A. Szucs andE. Csanda,Metiamide-treatment of brain oedema in animals exposed to 90yttriumirradiation, J. Pharm. Pharmac.28, 162–163 (1976).

    Google Scholar 

  22. L.J. Lichtenstein andE. Gillespie,The effects of H 1 and H 2 anti-histamines on allergic histamine release and its inhibition by histamine, J. Pharmac. exp. Ther.192, 441–450 (1975).

    Google Scholar 

  23. R.D. Krell andL.W. Chakrin.The effect of metiamide in vitro and in vivo canine models of type I hypersensitivity reactions, Eur. J. Pharmac.44, 35–44 (1977).

    Article  Google Scholar 

  24. J.M. Drazen, C.S. Venugopalan andN.S. Soter,H 2-receptor mediated inhibition of immediate type hypersensitivity reactions in vivo, Am. Rev. resp Dis.117, 479–485 (1978).

    PubMed  Google Scholar 

  25. R. Dulabh andM.R. Vickers,The effects of H 2-receptor antagonists on anaphylaxis in the guinea-pig, Agents and Actions8, 559–565 (1978).

    PubMed  Google Scholar 

  26. E.H. Herman andR.S.K. Young,Acute cardiovascular alterations induced by low doses of adriamycin, rubidazone and daunorubicin in the anesthetized beagle dog, Cancer Treat. Rep.63, 1771–1779 (1979).

    PubMed  Google Scholar 

  27. M.R. Bristow, W.S. Sageman, R.H. Scott, M.E. Billingham, R.E. Bowden, R.S. Kernoff, G.E. Snidow andS.R. Daniels,Acute and chronic cardiovascular effects of doxorubicin in the dog: the cardiovascular pharmacology of drug-induced histamine release, J. Cardiovasc. Pharmac.2, 487–515 (1980).

    Google Scholar 

  28. R.A. Levandowski,Doxorubicin and the heart, Ann. intern. Med.92, 866–867 (1980).

    PubMed  Google Scholar 

  29. E.A. Riegel, M. Kaliner, A.N. El-Hage, V.J. Ferrans, O. Kawanami andE.H. Herman,Anthracycline-induced histamine release from rat mast cells, Agents and Actions12, 431–437 (1982).

    Article  PubMed  Google Scholar 

  30. P.W. Askenase,Role of basophils, mast cells and vasoamines in hypersensitivity reactions with a delayed time course, Prog. Allergy23, 199–230 (1977).

    PubMed  Google Scholar 

  31. N.R. Lynch andJ.C. Salomon,Passive local anaphylaxis: Demonstration of antitumor activity and complementation of intratumor BCG, J. Natl. Cancer Inst.58, 1093 (1977).

    PubMed  Google Scholar 

  32. C. Burtin, P. Scheinmann, J.C. Salomon, G. Lespinats, F. Loisillier andP. Canu,The influence of intraperitoneal injections of histamine on tumour growth in fibrosarcoma-bearing mice, Cancer Letters12, 195–201 (1981).

    Article  PubMed  Google Scholar 

  33. C. Burtin, P. Scheinmann, J.C. Salomon, G. Lespinats andP. Canu,Decrease in tumour growth by injections of histamine or serotonin in fibrosarcoma-bearing mice: influence of H 1 and H 2 histamine receptors, Br. J. Cancer45, 54–60 (1982).

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Eschalier, A., Lavarenne, J., Renoux, M. et al. Cardiac and vascular effects of elliptinium in guinea pigs. Involvement of a histaminergic mechanism. Agents and Actions 16, 302–305 (1985). https://doi.org/10.1007/BF01982862

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01982862

Keywords

Navigation