Abstract
Guanidino compounds of guanidinoethanesulfonic acid, guanidinoacetic acid, guanidinosuccinic acid, N-acetylarginine, β-guanidinopropionic acid, creatinine, γ-guanidinobutyric acid, arginine, guanidine, methylguanidine, homoarginine and α-guanidinoglutaric acid are present in the mammalian brain. These guanidino compounds except for arginine and guanidine induce seizures and convulsions in rat, rabbit and cat by intracisternal injection.
Hirudonine, audonine, α-keto-δ-guanidinovaleric acid, N,N′-dibenzoylguanidine and phenylethylguanidine are also convulsants. Levels of creatinine, guanidinoethanesulfonic acid, creatinine, guanidinoacetic acid and methylguanidine in animal brain were changed at pre- and during convulsions induced by pentylentetrazol, amygdala kindling, iron-induced epileptogenesis and so on. These convulsions are thought to be due to depressed functions of serotonergic neurons and accumulated free radicals.
Arginine is a substrate of nitric oxide production by nitric oxide synthase. α-Guanidinoglutaric acid is a generator of superoxide, hydroxyl radicals and nitric oxide, and induced C6 glial cell death. On the other hand, aminoguanidine is a free radical scavenger. Energy formation by creatine metabolism may inhibit apoptosis induced by pathogenesis. Free radical generation/reaction and energy generation by guanidino compounds must be important key role in the brain.
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Jinnai D, Mori A, Mukawa J, Ohkusu H, Hosotani M, Mizuno A: Biochemical and physiological studies on guanidine compounds induced convulsion. Choong Jpn J Brain Physiol 106: 3668-3673, 1969
Mori A, Hiramatsu M, Takahashi K, Kohsaka M: Guanidino compounds in rat organs. Comp Biochem Physiol 51B: 143-144, 1975
Nakae I: Synthesis of N,N′-dibenzoylguanidine and its convulsive action. Neurosciences 7: 205-217, 1981
Shirakabe Y: Synthesis of phenylethylguanidine and its effects on neurotransmitters of mouse brain and electroencephalogram of cat. Neurosciences 8: 161-170, 1982
Mori A, Hiramatsu M, Numoto A, Robin Y: Action convulsante des derives diguanidiques, l'hirudonine l'arcaine et l'audonine. CR Soc Biol 175: 755-760, 1981
Marescau B, Hiramatsu M, Mori A: α-keto-γ-guanidinovaleric acid induced electroencephalographic epileptiform discharges in rabbits. Neurochem Pathol 1: 203-209, 1983
Mori A, Watanabe Y, Shindo S, Akagi M, Hiramatsu M: α-Guanidinoglutaric acid and epilepsy. In: A. Lowenthal, A. Mori, B. Marescau (eds). Urea Cycle Diseases. Plenum Press, New York, 1983, pp 465-470
Shiraga H, Hiramatsu M, Mori A: Convulsive activity of α-guanidinoglutaric acid and the possible involvement of 5-hydroxytryptamine in the α-guanidinoglutaric acid induced seizure mechanism. J Neurochem 47: 1832-1836, 1986
Hiramatsu C: Guanidino compounds in mouse brain II. Guanidino compound levels in brain in relation to convulsions. Okayama Igakkai Zasshi 92: 427-433, 1980 (in Japanese)
Hiramatsu M, Edamatsu R, Fujikawa N, Shirasu A, Yamamoto Y, Suzuki S, Mori A: Analyses of guanidino compounds in CSF collected by implanted catheter into cisterna magna; changes in guanidino compounds in CSF of rabbits during convulsion. Brain Res 455: 38-42, 1988
Willmore LJ, Sypert GW, Munson JB: Chronic focal epileptiform discharges induced by injection of iron into rat and cat cortex. Science 200: 1501-1503, 1978
Fukushima M: Guanidino compounds in iron-induced epileptogenic foci of rats. Okayama Igakkai Zasshi 99: 787-806, 1987 (in Japanese)
Hisayasu Y, Morimoto K, Otsuki S: Increase of methylguanidine and guanidinoacetic acid in the brain of amygdala-kindled rats. Epilepsia 32: 761-766, 1986
Hiramatsu M, Ohba S, Edamatsu R, Kadowaki D, Mori A: Effect of guanidino compounds on membrane fluidity of rat synaptosomes. In: P.P. Deyn, B. Marescau, V. Stalon, L.A. Qureshi (eds). Guanidino Compounds in Biology and Medicine. John Libbey & Co. Ltd., 1992, pp 387-393
Hiramatsu M, Niiya-Nishihara H, Mori A: Effect of taurocyamine on taurine and other amino acids in the brain, liver and muscle of mice. Neurosciences 8: 289-294, 1982
Hiramatsu M, Edamatsu R, Kohno M, Mori A: Scavenging of free radicals by Sho-saiko-to-go-keishi-kashakuyaku-to. In: E. Hosoya, Y. Yamamura (eds). Recent Advances in the Pharmacology of KAMPO Medicines. Excepter Medica, 1988, pp 120-127
Hiramatsu M, Edamatsu R, Kohno M, Mori A: The reactivity of guanidino compounds with hydroxyl radicals. In: A. Mori, B.D. Cohen, H. Koide (eds). Guanidines. Plenum Press, New York, 1989, pp 97-105
Mori A, Akagi M, Katayama Y, Watanabe Y: α-Guanidinoglutaric acid in cobalt-induced epileptogenic cerebral cortex of cats. J Neurochem 35: 603-605, 1980
Hiramatsu M, Komatsu M, Kido T: The relationship between reactive oxygen species and the α-guanidinoglutaric acid induced seizure mechanism. In: A. Mori, M. Ishida, J.F. Clark (eds). Guanidino Compounds: 5. Blackwell Science Asia Pty Ltd., 1999, pp 193-198
Hiramatsu M, Komatsu M: The detection of nitric oxide from α-guanidinoglutaric acid by hydroxyl radicals using an electron spin resonance method with spin trap. In: P.P. Deyn, B. Marescau, I.A. Qureshi, A. Mori (eds). Guanidino Compounds. John Libbey & Co. Ltd., 1997, pp 31-36
Seki S, Yuyama N, Hiramatsu M: Effect of guanidino compounds on hen egg development. In: A. Lowenthal, A. Mori, B. Marescau (eds). Urea Cycle Diseases. Plenum Press, New York, 1983, pp 465-470
Komatsu M, Hiramatsu M, Willmore LJ: Zonisamide reduces the increase in 8-hydroxy-2′-deoxyguanosine levels in the brain formed during iron-induced epileptogenesis in rats. Epilepsia 41: 1091-1094, 2000
Holtzman D, Kekelize T: Guanidino compounds in studies of brain ATP metabolism. In: A. Mori, M. Ishida, J.F. Clark (eds). Guanidino Compounds: 5. Blackwell Science Asia Pty Ltd., London, 1999 pp 3-15
Matthew RT, Kaddurah-Daouk R, Beal M: The neuroprotective effect of creatine and its analogs in animal models of neurodegenerative diseases. In: A. Mori, M. Ishida, J.F. Clark (eds). Guanidino Compounds: 5. Blackwell Science Asia Pty Ltd., London, 1999, pp 105-115
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Hiramatsu, M. A role for guanidino compounds in the brain. Mol Cell Biochem 244, 57–62 (2003). https://doi.org/10.1023/A:1022491419813
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DOI: https://doi.org/10.1023/A:1022491419813