Metrazol enhanced the penetration of two proteins (125I human serum albumin and horseradish peroxidase), and the anticancer agent, razoxane, into the central nervous system of anaesthetized rats. Penetration was increased throughout the whole brain. With the exception of the bladder, no peripheral tissue was affected. The increase in brain permeability was temporary and reversed within 4 hours; brain levels of drug and protein were increased by up to three times.[/p]
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Beleslin, D., Polak, R., and Sproull, D., 1965, The effect of leptazol and strychnine on the acetylcholine release from the cat brain. Journal of Physiology, 177, 308–316.
Bradbury, M., 1979, The Concept of a Blood-Brain Barrier (Chichester: John Wiley & Sons), pp. 351–382.
Crone, C., 1965, Permeability of brain capillaries to non electrolytes. Acta physiologica scandinavica, 64, 407–417.
Esplin, D., and Woodbury, D., 1956, The fate and excretion of C14-labelled pentylenetetrazol in the rat, with comments on analytical methods for pentylenetetrazol. Journal of Pharmacology and Experimental Therapeutics, 118, 129–138.
Fu, X., Collins, M., Greig, N., and Hellmann, K., 1982, Ultrafilter-HPLC assay method for pharmacokinetic and mechanism of action studies of razoxane. In preparation.
Greig, N., Fu, X., and HELLMANN, K., 1982, Razoxane penetration into the cerebrospinal fluid of rats. Cancer Chemotherapy and Pharmacology (in the press).
Gross, G. J., and Woodbury, D. M., 1972, Effects of pentylenetetrazol on ion transport in the isolated toad bladder. Journal of Pharmacology and Experimental Therapeutics, 181, 257–272.
Hanker, J., Yates, P., Metz, C., and Rustioni, A., 1977, A new specific, sensitive and non-carcinogenic reagent for the demonstration of horseradish peroxidase. Journal of Histochemistry, 9, 789–792.
Hasegawa, H., Allen, J., Mehta, B., Shapiro, W., and Posner, J., 1979, Enhancement of CNS penetration of methotrexate by hyperosmolar intracarotid mannitol or carcinomatous meningitis. Neurology, 29, 1280–1286.
Hellmann, K. Newton, K., Whitmore, D., Hanham, I., and Bond, J., 1969, Preliminary clinical assessment of ICRF 159 in acute leukaemia and lymphosarcoma. Nature, 222, 384–387.
Johansson, B., and Nilsson, B., 1977, The pathophysiology of the blood-brain barrier dysfunction induced by severe hypercapnia and by epileptic brain activity. Acta neuropathologica, 38, 153–158.
Johns, D. G., Farquhar, D., Wolpert, M., Chabner, B., and Loo, T., 1973, Dialkyl esters of methotrexate and 3′,5′-dichloromethotrexate synthesis and interaction with aldehyde oxidase and dihydrofolate reductase. Drug Metabolism Disposition, 1, 580–589.
Lee, J., and Olszewski, J., 1961, Increased cerebro vascular permeability after repeated electroshocks. Neurology, 11, 515–519.
Levin, V. A., 1975, A pharmacological basis of brain tumour chemotherapy. Seminars Oncology, 2, 57–61.
Levin, V. A., Freeman-Dove, M., and Landahl, H. D., 1975, Permeability characteristics of brain adjacent to tumours in rats.Archives of Neurology, 32, 785–791.
Lorenzo, A. V., Shirahige, M., Lang, M., and Barlow, C., 1972, Temporary alteration of cerebrovascular permeability to plasma proteins in drug-induced seizures. American Journal of Physiology, 223 (11), 268–277.
Lorenzo, A. V., Hedley-Whyte, T., Eisenberg, H., and Hsu, D., 1975, Increased penetration of horseradish peroxidase across the blood-brain barrier induced by Metrazol seizures. Brain Research, 88, 136–140.
Nair, V., and Roth, L. J., 1964, Effect of X-irradiation and certain other treatments on blood-brain barrier permeability, Radiation Research, 23, 249–264.
Ohno, K., Fredericks, W., and Rapoport, S., 1979, Osmotic opening of the blood-brain barrier to methotrexate in the rat. Surgical Neurology, 12, 323–328.
Rapoport, S., 1976, Blood-Brain Barrier in Physiology and Medicine (New York: Raven Press).
Rapoport, S., 1976, Modification of cerebrovascular permeability by hypertonic solutions and conditions which alter autoregulation of cerebral blood flow. The Cerebral Vessel Wall, edited by Cervos-Navarro (New York: Raven Press), pp. 215–223.
Rapoport, S., 1980, Quantitative aspects of osmotic opening of the blood-brain barrier, Brain Metastasis, edited by L. Weiss (Boston: Hall & Co.), pp. 100–115.
Pope, A., and Anfinsen, C., 1947, Histochemical and action potential studies on eleptogenic areas of cerebral cortex in man and monkey. Research Publication of the Association for Nervous and Mental Disorders, volume 26 (New York: Hafner Publishing Co.), pp. 218–233.
Reese, T. S., and Karnovsky, M. J., 1967, Fine structural localization of a blood-brain barrier to exogenous peroxidase. Journal of Cell Biology, 34, 207–217.
Sokoloff, L., 1977, Relationship between physiological function and energy metabolism in the central nervous system. Journal of Neurochemistry, 29, 13–26.
Tower, D., and Elliot, K., 1952, Activity of acetylcholine system in human eleptogenic focus. Journal of Applied Physiology, 4, 669–676.
Waggener, J. D., and Baggs, J. L., 1976, Vasculature of neural neoplasms, Advances in Neurology, edited by R. A. Thompson and J. R. Green (New York: Raven Press).
Walker, M. D., 1977, Treatment of brain tumours. Medical Clinics of North America, 61, 1045–1051.
Vick, N. A., and Bigner, D. D., 1972, Microvascular abnormalities in virally induced canine brain tumours: Structural bases for altered blood-brain barrier function. Journal of Neurological Science, 17, 29–39.
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Greig, N., Hellmann, K. Enhanced cerebrovascular permeability by Metrazol: significance for brain metastases. Clin Exp Metast 1, 83–95 (1983). https://doi.org/10.1007/BF00118475
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DOI: https://doi.org/10.1007/BF00118475