title: Endogenous guanidino compounds as uremic neurotoxins.
abstract: Epileptic and cognitive symptomatologies are among the most typical manifestations of uremic encephalopathy. Several guanidino compounds (GCs) may play an important role in the etiology of uremic encephalopathy. Four GCs appeared to be highly increased as well in serum, cerebrospinal fluid, and brain of uremic patients, whereas the levels of other metabolically relevant GCs were not or only moderately increased and others were even decreased. These highly increased compounds or "uremic" GCs are creatinine (CTN), guanidine (G), guanidinosuccinic acid (GSA), and methylguanidine (MG). All four compounds were shown to be experimental convulsants in brain concentrations similar to those found in uremic brain. We have described a possible mechanism for the contribution of GCs to uremic hyperexcitability, referring to the in vitro effects of uremic GCs on inhibitory and excitatory amino acid receptors. The excitatory effects of uremic GCs on the central nervous system may be explained by the activation of N-methyl-D-aspartate (NMDA) receptors by GSA, concomitant inhibition of GABA(A) receptors by uremic GCs, and other depolarizing effects. These effects might also indicate the putative contribution of uremic GCs to the etiology of uremic encephalopathy.
authors.affiliation: Department of Neurology, Middelheim Hospital, Wilrijk-Antwerp, Belgium.
authors.forename: P P
authors.initials: PP
authors.lastname: De Deyn
authors.forename: R
authors.initials: R
authors.lastname: D'Hooge
authors.forename: P P
authors.initials: PP
authors.lastname: Van Bogaert
authors.forename: B
authors.initials: B
authors.lastname: Marescau
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D001928:Brain Diseases, Metabolic / Q000209:etiology; D003292:Convulsants / Q000378:metabolism / Q000633:toxicity; D006146:Guanidines / Q000378:metabolism* / Q000633:toxicity; D006801:Humans; D008959:Models, Neurological; D009498:Neurotoxins / Q000378:metabolism* / Q000633:toxicity; D017459:Receptors, Amino Acid / Q000187:drug effects; D014018:Tissue Distribution; D014511:Uremia / Q000150:complications / Q000378:metabolism*
chemical_list: D003292:Convulsants; D006146:Guanidines; D009498:Neurotoxins; D017459:Receptors, Amino Acid