Skip to main content
SpringerLink
Log in

Biochemistry and neurotoxicology of guanidino compounds

History and recent advances

  • Published:
The Pavlovian Journal of Biological Science Aims and scope Submit manuscript

Abstract

Guanidino compounds are known to have important biological roles, such as the participation of arginine in ureagenesis, and of creatine in muscular contraction. On the other hand, the high toxicity of guanidino compounds, such as methylguanidine and guanidine, has been under study for quite a long time in the biochemical as well as clinical fields. In this review, the author summarizes the experimental results of neurophysiological and neurochemical studies on guanidino compound-induced seizures, conducted by his colleagues since 1966, and introduces several topics arising from their recent investigations on guanidino compounds and seizure mechanism,i.e., (1) α-guanidino-glutaric acid in the cobalt epileptic focus and its convulsive activity; (2) guanidino-ethanesulfonic acid and epilepsy; (3) δ-guanidinovaleric acid, and endogenous and specific GABA receptor antagonist; and (4) guanidino compounds as radical generators.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Andes, J. E., and Myers, V. (1937) Guanidine-like substances in blood.The Journal of Laboratory and Clinical Medicine, 22, 1147–1154.

    Google Scholar 

  • Baker, L. R. I., and Marshall, R. D. (1971) A reinvertigation of methylguanidine concentration in sera from normal and uremic subjects.Clinical Science, 41, 563–568.

    PubMed  Google Scholar 

  • Brieger, L. (1886) Über Ptomaine3, 38–39; cited from Brieger (1897).

    Google Scholar 

  • Brieger, L. (1897) Zur Kenntniss der Stoffwechselproducte des Cholerabacillus.Klinische Wochenschrift, 44, 317–820.

    Google Scholar 

  • Chevreul, M. (1835) Sur la composition chemique du bouillon de viande,Journal of Pharmaceutical Sciences, 21, 231; cited from Robin and Marescau (1985).

    Google Scholar 

  • Cohen, B. D., Stein, I. M., and Bonas, J. E. (1968) Guanidinosuccinic aciduria in uremia. A possible alternate pathway for urea cycle.American Journal of Medicine, 45, 63–68.

    Article  PubMed  Google Scholar 

  • Edaki, A., Watanabe, Y., Yokoi, I., Shirags, H., Fujii, T., and Mori, A. (1986) 2-Guanidinoethanol-induced convulsive seizures in rat.Neurosciences, 12, 106–107.

    Google Scholar 

  • Eggleton, P., and Eggleton, G. P. (1927) Inorganic phosphate and a labile form of organic phosphate in the gastrocnemius of the dog.Biochemical Journal, 21, 190.

    PubMed  Google Scholar 

  • Frank, E., Streen, R., and Nothmann, M. (1921) Die Guanidin-und Dimethylguanidin-Toxikose des Saugetiers und ihre physiopathologische Bedeutung.Zeitschrift für die Gesamte Experimentelle Medizin, 24, 341–370.

    Article  Google Scholar 

  • Fühner, H. (1907) Curarestudien I. Die periphere Wirkung des Guanidins.Archiv für experimentelle Pathologie und Pharmacologie, 50, 1–49.

    Article  Google Scholar 

  • György, P., and Vollmer, H. (1922) Beeinflussung der Guanidinvergiftung durch Saurezufuhr.Archiv für experimentelle Pathologie und Pharmacologie, 95, 200–205.

    Article  Google Scholar 

  • Hoffmann, A. W. (1866) Hr. Hofmann las über Synthesen des Guanidins.Monatsberichte der Berliner Akademie, 148–156.

  • Hoffmann, A. W. (1868) Zur Kenntniss des Guanidins.Berichte der Deutschen Chemischen Gesellschaften, 1, 145–147.

    Article  Google Scholar 

  • Jinnai, D., Sawi, A., and Mori, A. (1966) γ-Guanidinobutyric acid as a convulsive substance.Nature, 212, 617.

    Article  PubMed  Google Scholar 

  • Jinnai, D., Mori, A., Mukawa, J., Ohkusu, H., Hosotani, M., Mizuno, A., and Tye, L.C. (1969) Biochemical and physiological studies on guanidino compounds induced convulsion.Japanese Journal of Brain Physiology, 106, 3668–3673.

    Google Scholar 

  • Koch, W. F. (1912) On the occurrence of methyl guanidine in the urine of parathyroidectomized animals.Journal of Biological Chemistry, 12, 313–315.

    Google Scholar 

  • Koch, W. F. (1913) Toxic bases in the urine of parathyroidectomized dogs.Journal of Biological Chemistry, 15, 43–63.

    Google Scholar 

  • Krebs, H. A., and Henseleit, K. (1932) Untersuchungen über die Harnstoffbildung im Tierkörper.Zeitschrift der Physiologischen Chemie, 210, 33.

    Google Scholar 

  • Kuen, F. M. (1927) Über die Bestimmung der Guanidine und über des angebliche Vorkommen derselben im Tetanierharn.Biochemische Zeitschrift, 187, 283–306.

    Google Scholar 

  • Major R. H., and Weber, C. J. (1927) The possible increase of guanidine in the blood of certain persons with hypertension.Archives of Internal Medicine, 40, 891–899.

    Google Scholar 

  • Marescau, B., Hiramatsu, M., and Mori, A. (1983) α-Keto-δ-guanidinovaleric acid-induced electroencephalographic epileptiform discharges in rabbits.Neurochemical Pathology, 1, 203–209.

    Article  Google Scholar 

  • Matsumoto, M., Kobayashi, K. Kishikawa, H., and Mori, A. (1976) Convulsive activity of methylguanidine in cat and rabbits.IRCS Medical Science, 4, 65.

    Google Scholar 

  • Matsumoto, M., and Mori, A. (1976) Effects of guanidino compounds on rabbit brain microsomal Na+- K+-ATPase activity.Journal of Neurochemistry, 27, 635–636.

    Article  PubMed  Google Scholar 

  • Mastsumoto, M., Fujiwara, M., Mori, A., and Robin, Y. (1977) Effect des dérivés guanidiques sur la cholinacétylase et sur l’acetylcholinestérase du cerveau de lapin.Comptes Rendus des Séances Société de Biologie et de ses Filiales, 171, 1226–1229.

    Google Scholar 

  • Minichini, G. C., Gonelia, M., Barsotti, G., and Givannetti, S. (1971) Determination of methylguanidine in serum and urine from normal and uremic subjects.Experientia, 27, 1157–1158.

    Article  Google Scholar 

  • Mizuno, A., Mukawa, J. Kobayashi, K., and Mori, A. (1975) Convulsive activity of taurocyamine in cats and rabbits.IRCS Medical Science, 3, 385.

    Google Scholar 

  • Mori, A., and Ohkusu, H. (1971) Isolation of α-N-acetyl-L-arginine from calf brain and convulsive seizure induced by this substance.Advances in Neurological Sciences (Shinkei Kenkyu no Shinpo), 15, 303–306 (in Japanese).

    Google Scholar 

  • Mori, A., Akagi, M. Katayama, Y., and Watanabe, Y. (1980) α-Guanidinoglutaric acid in cobalt-induced epileptogenic cerebral cortex of cats.Journal of Neurochemistry, 35, 603–705.

    Article  PubMed  Google Scholar 

  • Mori, A., Katayama, Y. Yokoi, I., and Matsumoto, M. (1981) Inhibition of taurocyamine (guanidino-taurine)-induced seizures by taurine. In S. W. Schaffer, S. I. Baskin, and J. J. Kocsis (Eds.),The Action of Taurine on Excitable Tissues. New York: Spectrum Publications.

    Google Scholar 

  • Mori, A. Watanabe, Y, and Akagi, M. (1982) Guanidino compound anomalies in epilepsy. In H. Akimoto, H. Kazamatsuri, M. Seino, and A. Ward (Eds.),Advances in Epileptology: XIIIth Epilepsy International Symposium. New York: Raven Press.

    Google Scholar 

  • Mori, A., Watanabe, Y., and Fujimoto, N. (1982) Fluorometrical analysis of guanidino compounds in human cerebrospinal fluid.Journal of Neurochemistry, 38, 448–450.

    Article  PubMed  Google Scholar 

  • Murry, M., and Hofmann, A. B. (1940) The occurrence of guanidine-like substances in the blood in essential epilepsy.The Journal of Laboratory and Clinical Medicine, 25, 1072–1073.

    Google Scholar 

  • Nattrass, F. J., and Sharpe, J. S. (1921) Adolescent tetany and its relation to guanidin.The British Medical Journal, 2, 238–239.

    Article  Google Scholar 

  • Nelken, L. (1932) Über den Einfluss der Guanidinvergiftung auf den Calcium und Phosphatgehalt des Blutes.Klinische Wochenschrift, 1, 261.

    Google Scholar 

  • Noël Paton, D., and Findlay, L. (1917) The Parathyroid:—Tetania parthyreopriva: Its nature, cause, and relation to idiopathic tetany. Part IV: The etiology of the condition and its relationship to guanidin and methylguanidin intoxication.Quarterly Journal of Experimental Physiology, 10, 315–344.

    Google Scholar 

  • Palmer, H. D., McNairScott, D. B., and Elliott, K.A.C. (1943) A note on the blood guanidine level in migraine subjects.Journal of Laboratory and Clinical Medicine, 28, 735–737.

    Google Scholar 

  • Robin, Y., and Marescau, B. (1985) Natural guanidino compounds. In A. Mori, B. D. Cohen, and A. Lowenthal (Eds.),Guanidines: Historical, Biological, Biochemical and Clinical Aspects of the Naturally Occurring Guanidino Compounds. New York and London: Plenum Press.

    Google Scholar 

  • Schulze, E. (1892) Ueber das Vorkommen von Guanidin im Pflanzenorganismus.Berichte der Deutschen Chemischen Gesellschaften, 65, 658–661.

    Article  Google Scholar 

  • Sharpe, J. S. (1920) The guanidine content of feces in idiopathic tetany.Biochemical Journal, 14, 46–47.

    PubMed  Google Scholar 

  • Shindo, S., Tsuruta, K., Yokoi, I., and Mori, A. (1984) Synthesis of δ-guanidinovaleric acid and its effect on EEG of rats.Neurosciences, 10, 197–182.

    Google Scholar 

  • Shiraga, H., and Mori, A. (1982) Convulsive activity of α-guanidinoglutaric acid in rats.IRCS Medical Science, 10, 855–856.

    Google Scholar 

  • Shiraga, H., Hiramatsu, M., and Mori, A. (1986) Convulsive activity of α-giuanidinoglutaric acid and the possible involvement of 5-hydroxytryptamine in the α-guanidinoglutaric acid-induced seizure mechanism.Journal of Neurochemistry, 47, 1832–1836.

    Article  PubMed  Google Scholar 

  • Stein, I. M., Perez, G., Johnson, R., and Cummings, N. B. (1971) Serum levels and urinary excretion of methylguanidine in chronic renal failure.The Journal of Laboratory and Clinical Medicine, 77, 1920–1924.

    Google Scholar 

  • Strecker, A. (1861) Untersuchungen über die chemischen Beziehung zwischen Guanin, Xanthin, Teobromin, Caffein und Kreatin.Annalen der Chemie und Pharmacie, 118, 151–177.

    Article  Google Scholar 

  • Terheggen, H. G., Schwenk, A., Lowenthal, A., Van Sanke, M., and Colombo, J. P. (1969) Argininemia with arginase deficiency.Lancet, 2, 748–749.

    Article  Google Scholar 

  • Watanabe, Y., Sindo, S., and Mori, A. (1985) Identification of 2-guanidinoethanol in human urine.European Journal of Biochemistry, 147, 465–468.

    Article  PubMed  Google Scholar 

  • Westall, R. G. (1960) Argininosuccinic aciduria: Identification and reactions of the abnormal metabolite in a newly described form of mental disease, with some preliminary metabolic studies.Biochemical Journal, 77, 135–160.

    PubMed  Google Scholar 

  • Yokoi, I., Toma, J., and Mori, A. (1984) The effect of homoarginine on the EEG of rats.Neurochemical Pathology, 2, 295–300.

    PubMed  Google Scholar 

  • Yokoi, I., Watanabe, Y., and Mori, A. (1986) Identification of δ-guanidinovaleric acid in human urine. Seikagaku,58, 1007 (in Japanease).

    Google Scholar 

  • Yokoi, I. Tsuruta, K., Siraga, H., and Mori, A. (1987) δ-Guanidinovaleric acid as an endogeneous and specific GABA-receptor antagonist: Electroencephalographic study.Epilepsy Research, 1, 40–45.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurochemistry, Institute for Neurobiology, Okayama University Medical School, 2-5-1, Shikatacho, 700, Okayama, Japan

    Akitane Mori M.D., Ph.D.

Authors
  1. Akitane Mori M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mori, A. Biochemistry and neurotoxicology of guanidino compounds. Pav. J. Biol. Sci. 22, 85–94 (1987). https://doi.org/10.1007/BF02734659

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02734659

Keywords

Search

Navigation