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.
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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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
S. Wallenstein, C.L. Zucker andJ.L. Fleiss,Some statistical methods useful in circulation research, Circulation Res.47, 1–9 (1980).
R.W. Brimblecombe, D.A.A. Owen andM.E. Parsons,The cardiovascular effects of histamine in laboratory animals, Agents and Actions4, 191–192 (1974).
H.H. Dale andP.P. Laidlaw,The physiological action of betaiminazolylethylamine, J. Physiol., Lond.41, 318–344 (1910).
J.H. Burn andH.H. Dale,The vasodilator action of histamine and its physiological significance, J. Physiol., Lond.61, 185–214 (1926).
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).
E.R. Loew,Pharmacology of antihistamine compounds, Physiol. Rev.27, 542–573 (1947).
W.G. Spector andD.A. Willoughby,The antagonism of substances that increase vascular permeability in the rat, J. Path.86, 487–496 (1963).
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).
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).
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).
F. Joo, A. Szucs andE. Csanda,Metiamide-treatment of brain oedema in animals exposed to 90yttriumirradiation, J. Pharm. Pharmac.28, 162–163 (1976).
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).
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).
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).
R. Dulabh andM.R. Vickers,The effects of H 2-receptor antagonists on anaphylaxis in the guinea-pig, Agents and Actions8, 559–565 (1978).
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).
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).
R.A. Levandowski,Doxorubicin and the heart, Ann. intern. Med.92, 866–867 (1980).
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).
P.W. Askenase,Role of basophils, mast cells and vasoamines in hypersensitivity reactions with a delayed time course, Prog. Allergy23, 199–230 (1977).
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).
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).
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).
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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
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DOI: https://doi.org/10.1007/BF01982862