title: The uremic guanidino compound guanidinosuccinic acid induces behavioral convulsions and concomitant epileptiform electrocorticographic discharges in mice.
abstract: As yet, the in vivo epileptogenic properties of guanidinosuccinic acid (GSA) remained highly conjectural, still requiring the demonstration of GSA-induced behavioral convulsions accompanied by epileptiform electrographic discharges. Therefore, Swiss mice were injected intraperitoneally (i.p.) with increasing doses of GSA. Full-blown clonic or clonic-tonic convulsions appeared in a dose-dependent manner, with a median latency of about 25 min. CD50 (convulsive dose of the drug in 50% of the animals), the LD50 (lethal dose in 50%), and their 95% confidence limits for GSA suspensions in i.p. administration were 363 (287-458) mg/kg and 579 (445-756) mg/kg, respectively. In addition, four-channel electrocorticographic (ECoG) recordings were made in freely moving mice following the injection of 700 mg/kg (CD97). Epileptiform ECoG discharges coincided with the behavioral manifestation of the GSA-induced convulsions starting with initial decrease in amplitude, occasional spike-waves (10-20 min after injection), eventually leading to sustained spiking and spike-wave activity (30-50 min after injection). Clonic convulsions induced by a CD97 dose of GSA were only moderately attenuated by high doses of i.p. phenobarbital (20, 40 and 80 mg/kg), while tonic extension and lethal effects were dose-dependently blocked. A dose of 1000 mg/kg (CD97 for tonic extension) induced tonic extension in 100% of the animals, following treatment with 20 mg/kg of phenytoin none of the animals displayed tonic extension, and following 10 mg/kg only 30% of the animals displayed tonic extension, while the occurrence of clonic convulsions was not significantly attenuated.
authors: Laboratory of Neurochemistry and Behavior, Born-Bunge Foundation, University of Antwerp (UIA), Belgium.
authors: R
authors: R
authors: D'Hooge
authors: Y Q
authors: YQ
authors: Pei
authors: J
authors: J
authors: Manil
authors: P P
authors: PP
authors: De Deyn
mesh_terms: D000818:Animals; D003292:Convulsants / Q000633:toxicity*; D004569:Electroencephalography / Q000187:drug effects*; D004827:Epilepsy / Q000139:chemically induced*; D005260:Female; D006146:Guanidines / Q000633:toxicity*; D008297:Male; D051379:Mice; D013386:Succinates / Q000633:toxicity*; D014511:Uremia / Q000378:metabolism*
chemical_list: D003292:Convulsants; D006146:Guanidines; D013386:Succinates; C001318:guanidinosuccinic acid