Advertisement

Comparative evaluation of the hypotensive activity of two major metabolites of hydralazine (1-hydrazinophthalazine)

  • A. J. Mclean
  • K. D. Haegele
  • P. Du Souich
  • J. L. Mcnay
Original Papers

Summary

Triazolophthalazine (TP) and hydralazine-acetonide (HA) are important hydralazine metabolites in rat. Conscious rats chronically implanted with aortic and jugular venous catheters, were injected with these metabolites while blood pressure was recorded. TP was inert but HA produced dose-dependent hypotensive effects. HA may contribute to the unexplained, prolonged hypotensive effects of hydralazine.

Key-words

Hydralazine Hydralazine acetonide Triazolophthalazine in vivo comparison 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. (1).
    Carey, R.M., Reid, R.A., Ayers, C.R., Lynch, S.S., McLain, W.L., and Vaughan, E.D., (1976). “The Charlottesville Blood Pressure Measurements.” JAMA,236, 847–851.CrossRefPubMedGoogle Scholar
  2. (2).
    Veterans Administration Cooperative Study Group on Antihypertensive Agents. (1970). “Effects of treatment on morbidity and mortality. II Results in patients with diastolic blood pressure averaging 90 through 114 mm Hg.” JAMA,213, 1143–1152.CrossRefGoogle Scholar
  3. (3).
    Zacest, R., Gilmore, E., and Koch-Weser, J., (1972). “Treatment of essential hypertension with combined vasodilation and beta-adrenergic blockade.” New Engl. J. Med.,286, 617–622.CrossRefPubMedGoogle Scholar
  4. (4).
    Gottlieb, T.B., Thomas, C.B., and Chidsey, C.A., (1972). “Pharmacokinetic studies of minoxidil.” Clin. Pharm. Ther.,13, 436–441.Google Scholar
  5. (5).
    O’Malley, K., Segal, J.L., Israili, Z.H., Boles, M., McNay, J.L., and Dayton, P.G., (1975). “Duration of hydralazine action in hypertension.” Clin. Pharm. Ther.,18, 581–586.Google Scholar
  6. (6).
    Perry, H.M., (1973). “Late toxicity to hydralazine resembling systemic lupus erythematosus or rheumatoid arthritis.” Am. J. Med.,54, 58–72.CrossRefPubMedGoogle Scholar
  7. (7).
    Koch-Weser, J., (1976). “Hydralazine.” New Engl. J. Med.,295, 320–323.CrossRefPubMedGoogle Scholar
  8. (8).
    Schulert, A.R., (1961). “Physiological Disposition of Hydralazine and a Method for its Determination in Biological Fluids.” Arch. Int. Pharmacodyn.,132, 1–15.PubMedGoogle Scholar
  9. (9).
    Zacest, R. and Koch-Weser, J., (1972). “Relation of hydralazine plasma concentration to dosage and hypotensive action.” Clin. Pharm. Ther.,13, 420–425.Google Scholar
  10. (10).
    Reidenberg, M.M., Drayer, D., DeMarco, A.L., and Bello, C.T., (1973). “Hydralazine Elimination in Man.” Clin. Pharm. Ther.,14, 970–977.Google Scholar
  11. (11).
    Mclsaac, W.M. and Kanda, M., (1964). “The Metabolism of 1-Hydrazin-ophthalazine.” J. Pharm. Exp. Ther.,143–44, 7–13.Google Scholar
  12. (12).
    Zak, S.B., Bartlett, M.F., Wagner, W.E., Gilleran, T.G., and Lukas, G., (1974). “Disposition of Hydralazine in man and a specific method for its determination in biological fluids.” J. Pharm. Sci.,63, 225–229.CrossRefPubMedGoogle Scholar
  13. (13).
    Jack, D.B., Brechbiihler, S., Degen, P.H., Zbinden, P., and Riess, W., (1975). “The Determination of Hydralazine in Plasma by Gas-Liquid Chromatography.” J. Chromatography,775, 87–92.CrossRefGoogle Scholar
  14. (14).
    Haegele, K.D., Skrdlant, H.B., Robie, N.W., Lalka, D., and McNay, J.L., (1976). “Determination of Hydralazine and its Metabolites by Gas Chromatography-Mass Spectrometry.” J. Chromatography,126, 517–534.CrossRefGoogle Scholar
  15. (15).
    Druey, J. and Marxer, A., (1959). “Hypotensive Hydrazino-phthalazines and Related Compounds.” J. Med. Pharm. Chem.,7, 1–21.CrossRefGoogle Scholar
  16. (16).
    Weeks, J.R. and Jones, J.A., (1960). “Routine direct measurement of arterial blood pressure in unanesthetized rats.” Proc. Soc. Exp. Biol. Med.,104, 646–648.PubMedGoogle Scholar
  17. (17).
    Keberle, H., Faigle, J.W., Hedwall, P., Riess, W., and Wagner, J., (1972). “Plasma concentrations and pharmacological response in animals.”in Biological effects of drugs in relation to their plasma concentrations (eds. Davies, D.S. and Pritchard, B.N.C.), pp. 13–24, University Park Press, Baltimore, London, Tokyo.Google Scholar
  18. (18).
    Scriabine, A., Ludden, C.T., and Bohidar, N.T., (1974). “Potentiation of the antihypertensive action of hydralazine by Timolol in spontaneously hypertensive rats.” Proc. Soc. Exp. Biol. Med.,146, 509–512.PubMedGoogle Scholar
  19. (19).
    Zak, S.B., Gilleran, T.G., Karliner, J., Lukas, G., (1974). “Identification of two new metabolites of hydralazine from human urine.” J. Med. Chem.,77, 381–382.CrossRefGoogle Scholar
  20. (20).
    Zimmer, H., Glaser, R., Kokosa, J., Garteiz, D.A., Hess, E.V., and Litwin, A., (1975). “3-Hydroxymethyl-s-triazolo (3,4-Oc) phthalazine, a novel urinary hydralazine metabolite in man.” J. Med. Chem.,18, 1031–1033.CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 1977

Authors and Affiliations

  • A. J. Mclean
    • 1
    • 2
    • 3
    • 4
  • K. D. Haegele
    • 1
    • 2
    • 3
    • 4
  • P. Du Souich
    • 1
    • 2
    • 3
    • 4
  • J. L. Mcnay
    • 1
    • 2
    • 3
    • 4
  1. 1.Division of Clinical Pharmacology and Hypertension, Department of MedicineThe University of Texas Health Science CenterSan AntonioU.S.A.
  2. 2.Division of Clinical Pharmacology and Hypertension, Department of PharmacologyThe University of Texas Health Science CenterSan AntonioU.S.A.
  3. 3.Division of Clinical Pharmacology and Hypertension, Department of PathologyThe University of Texas Health Science CenterSan AntonioU.S.A.
  4. 4.Audie L. Murphy Memorial Veterans Administration HospitalSan AntonioU.S.A.

Personalised recommendations