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Toxicological evaluation of imipramine in combination with adriamycin and strophanthin

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Abstract

Chronic oral administration of imipramine to rats caused characteristic changes of the electrocardiogram (ECG), i.e. prolongation of the PR interval, widening of the QRS complex, and increase in T-wave voltage. The cardiotoxic anthracycline antibiotic adriamycin induced dose-dependent widening of the QRS complex. This effect on intraventricular conduction was not enhanced in rats receiving both drugs. The high adriamycin dose (5×4 mg/kg) abolished imipramine-induced prolongation of the PR interval and T-wave elevation. This was not seen with the low adriamycin dose (20×1 mg/kg). Imipramine prolonged survival time of rats treated with toxic doses of adriamycin, but enhanced growth retardation in animals receiving the low adriamycin dose.

Chronic treatment with increasing doses of strophanthin induced significant flattening of the T wave in rats with and without imipramine therapy, but did not influence the changes of the ECG or body weight gain caused by imipramine.

It is concluded that the combined use of imipramine and adriamycin or strophanthin did not lead to a serious enhancement of the toxicity of the tricyclic antidepressant.

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References

  1. C.S. Alexander andA. Niño,Cardiovascular Complications in Young Patients Taking Psychotropic drugs. A Preliminary Report, Amer. Heart J.78, 757–769 (1968).

    Google Scholar 

  2. T. Moccetti, P. Lichtlen, H. Albert, E. Meier andP. Imbach,Kardiotoxizität der trizyklischen Antidepressiva (Phenothiazine und Imipraminderivate), Schweiz, Med. Wschr.101, 1–10 (1971).

    Google Scholar 

  3. N. Serafimovski, N. Thorball, I. Asmussen andM. Lunding,Tricyclic Antidepressive Poisoning with Special Reference to Cardiac Complications, Acta Anesthesiol. Scand. (Suppl. 57), 55–63 (1975).

    Google Scholar 

  4. E.S. Kristiansen,Cardiac Complications during Treatment with Imipramin (Tofranil), Acta psychiat. neurol. Scand.36, 427–442 (1961).

    Google Scholar 

  5. O.F. Muller, N. Goodman andS. Bellet,The Hypotensive Effect of Imipramine Hydrochloride in Patients with Cardiovascular Disease, Clin. Pharm. Therap.2, 300–307 (1961).

    PubMed  Google Scholar 

  6. M. Schou,Electrocardiographic Changes during Treatment with Lithium and with Drugs of the Imipramine-type, Acta psychiat. neurol. Scand.39, Suppl. 169, 258–259 (1963).

    Google Scholar 

  7. J. Vohra andG. D. Burrows,Cardiovascular Complications of Tricyclic Antidepressant Overdosage, Drugs8, 432–437 (1974).

    PubMed  Google Scholar 

  8. G.I. Martin andP.J. Zaug,Electrocardiographic Monitoring of Enuretic Children Receiving Therapeutic Doses of Imipramine, Am. J. Psychiatry132, 540–542 (1975).

    PubMed  Google Scholar 

  9. J. Vohra, G.D. Burrows andG. Sloman,Assessment of Cardiovascular Side-Effects of Therapeutic Doses of Tricyclic Anti-depressant Drugs, Aust. N.Z.J. Med.5, 7–11 (1975).

    PubMed  Google Scholar 

  10. D. Burckhardt, H.J. Fleischhauer, I. Müller andH.W. Neubauer,Beitrag zur Wirkung tri- und tetrazyklischer Antidepressiva auf Herz und Kreislauf, Schweiz. Med. Wschr.106, 1896–1903 (1976).

    PubMed  Google Scholar 

  11. G.D. Burrows, J. Vohra, D. Hunt, J.G. Sloman, B.A. Scoggins andB. Davies,Cardiac Effects of Different Tricyclic Antidepressant Drugs, Brit. J. Psychiat.129, 335–341 (1976).

    PubMed  Google Scholar 

  12. G.E. Crane,Cardiac Toxicity and Psychotropic Drugs, Dis. nerv. syst.31, 534–539 (1970).

    PubMed  Google Scholar 

  13. D.C. Moir, J. Crooks, W. B. Cornwell, K. O'Malley, I. Dingwall-Fordyce, M.J. Turnbull andR.D. Weir,Cardiotoxicity of Amitriptyline Lancet2, 561–564 (1972).

    PubMed  Google Scholar 

  14. J.W. Jefferson,A Review of the Cardiovascular Effects and Toxicity of Tricyclic Antidepressants, Psychosom. Med.37, 160–179 (1975).

    PubMed  Google Scholar 

  15. G. Zbinden andE. Brändle,Toxicologic Screening of Daunorubicin (NSC-82151), Adriamycin (NSC-123127), and their Derivatives in Rats, Cancer Chemother. Rep. (Part 1),59, 707–715 (1975).

    Google Scholar 

  16. P. Lechat, M.C. Auclair andM. Adolphe,Comparative Effects of Chlorpromazine and Imipramine on Cultured Heart Cells of the Rat, Proc. Europ. Soc. Study Drug Tox.14, 214–221 (1972).

    Google Scholar 

  17. P. Lechat, M.C. Auclair andM. Adolphe,Effects comparés de divers compsés tricycliques sur les cultures de cellules cardiaques de rat, C.R. Soc. Biol.168, 6–7 (1974).

    Google Scholar 

  18. P. Lechat, M.C. Auclair andM. Adolphe,Effect of Imipramine on Cultured Rat Heart Cells, Toxicol. Appl. Pharmacol.27, 336–341 (1974).

    PubMed  Google Scholar 

  19. S.G. Dahl andH. Refsum,Effects of Levomepromazine, Chlorpromazine and their Sulfoxides on Isolated Rat Atria, Europ. J. Pharmacol.37, 241–248 (1976).

    Google Scholar 

  20. P. Dumovic, G.D. Burrows, J. Vohra, B. Davies andB.A. Scoggins,The Effect, of Tricyclic Antidepressant Drugs on the Heart, Arch. Toxicol.35, 255–262 (1976).

    PubMed  Google Scholar 

  21. E.B. Sigg, M. Osborne andB. Korol,Cardiovascular Effects of Imipramine, J. Pharmac. exp. Ther.141, 237–243 (1963).

    Google Scholar 

  22. H. Brunner, P.R. Hedwall andH.J. Bein,Cardiovascular Effects of Preparation CIBA 34, 276-BA and Imipramine, Agents and Actions2, 69–82 (1971).

    PubMed  Google Scholar 

  23. J.P. Buckley, M.L. Steenberg, B.S. Jandhyala andJ.M. Perel,Effects of Imipramine, Desmethyl-imipramine and their 2-OH Metabolites on Hemodynamics and Myocardial Contractility in Dogs, Fed. Proc.34, 450 (1975).

    Google Scholar 

  24. G. Zbinden, E. Bachmann, Ch. Holderegger andJ. Elsner,Cardiotoxicity of Tricyclic Antidepressants and Neuroleptic Drugs, Paper presented at the 1st Congress on Toxicology, Toronto, Canada, March 30-April 2, 1977.

  25. A. Di Marco, M. Gaetani andB. Scarpinato,Adriamycin: A new Antibiotic with Antitumor Activity, Cancer Chemother. Rep. (Part 1),53, 33–37 (1969).

    Google Scholar 

  26. G. Bonadonna, S. Monfardini, M. De Lena andE. Fossati-Bellani,Clinical Evaluation of Adriamycin, a new Antitumor Antibiotic, Br. Med. J.3, 503–506 (1969).

    PubMed  Google Scholar 

  27. R.H. Blum andS.K. Carter,Adriamycin, A New Anticancer Drug with Significant Clinical Activity, Ann Intern. Med.80, 249–259 (1974).

    PubMed  Google Scholar 

  28. R.S. Jaenke,An Anthracycline Antibiotic-Induced Cardiomyopathy in Rabbits, Lab. Invest.30, 292–304 (1974).

    PubMed  Google Scholar 

  29. E.A. Lefrak, J. Pitha, S. Rosenheim R.M. O'Bryan, M.A. Burgess andJ.A. Gottlieb,Adriamycin (NSC-123127) Cardiomyopathy, Cancer Cemother. Rep. (Part 3),6, 203–214 (1975).

    Google Scholar 

  30. R.A. Minow, R.S. Benjamin andJ.A. Gottlieb,Adriamycin (NSC-123127) Cardiomyopathy — An Overview with Determination of Risk Factors, Cancer Chemother. Rep. (Part 3).,6, 195–201 (1975).

    Google Scholar 

  31. L.H. Schmidt,The Cardiotoxicity of Adriamycin as Exhibited in the Rhesus Monkey, Paper presented at the Working Symposium on Anthracycline Antibiotics, National Cancer Institute, Division of Cancer Treatment, April 22–23, 1976.

  32. A.R. Ladder andP. Somani,Desipramine Toxicity and its Treatment, Toxicol. Appl. Pharmacol.15, 287–294 (1969).

    PubMed  Google Scholar 

  33. T. Attree, P. Sawyer andM.J. Turnbull,Interaction between Digoxin and Tricyclic Anti-depressants in the Rat, Europ. J. Pharmacol.19, 294–296 (1972).

    Google Scholar 

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Dedicated to K. Bucher on the occasion of his 65th birthday.

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Zbinden, G., Elsner, J. & Bolliger, H. Toxicological evaluation of imipramine in combination with adriamycin and strophanthin. Agents and Actions 7, 341–346 (1977). https://doi.org/10.1007/BF01969566

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