A guanidino compound with epileptogenic activity
N-Amidino-L-aspartic acid is a guanidino compound found in mammalian sera and the CNS.1 It induces whole-cell currents in rat hippocampal slices, an effect that can be reversed by the NMDA receptor antagonists D-AP5 and ketamine. Intrahippocampal administration of N-amidino-L-aspartic acid induces status epilepticus and neuronal cell death in rats.2 Cerebrospinal fluid and serum levels of N-amidino-L-aspartic acid are increased in patients with renal failure.1,2
1.D'Hooge, R., Raes, A., Lebrun, P., et al.N-methyl-D-aspartate receptor activation by guanidinosuccinate but not by methylguanidine: Behavioural and electrophysiological evidenceNeuropharmacology35(4)433-440(1996) 2.Pan, J.C., Pei, Y.Q., An, L., et al.Epileptiform activity and hippocampal damage produced by intrahippocampal injection of guanidinosuccinic acid in ratNeurosci. Lett.209(2)121-124(1996)
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Animal experiment: |
Mice[2]Randomly bred Swiss mice (male and female, body weight 13-25 g for the first series of experiments) are housed under standard environmentally controlled conditions. For another series of experiments, young Swiss mice 7, 14 and 21 days old are used. Injections of Guanidinosuccinic acid suspensions are delivered in volumes of 0.1 mL per 10 g body weight, i.p. and in doses between 250 and 1000 mg/kg (5 mice per dose, in duplicate). After injection, the mice are put in individual cylindrical transparent cages and observed for 1 h (for 2 h in the case of the young mice). Both CD50 and LD50 are calculated by probit analysis or moving average interpolation[2]. |
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参考文献: [1]. Milstien S, et al. Role of intestinal microflora in the metabolism of guanidinosuccinic acid. J Bacteriol. 1973 May;114(2):641-4. |
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