2-Guanidinoethanolのけいれん誘発作用に関する生理学的研究

The CNS action of 2-guanidinoethanol (GEt), that has been identified in human urine, was investigated in male S.D. rats. Effects of GABA (1 μmol, on the pia mater), diazepam (DZP)(10mg/kg, i.p.), muscimol (50 nmol, on the pia mater), (3R)-(-)-4-amino-3-hydroxybutanoic acid ((L)-GABOB)(1 μmol, on the pia mater), phenobarbital (PB) (20mg/kg, i.m.), dephenylhydantoin (PHT)(25mg/kg, i.p.) or valproate (VPA)(200mg/kg, i.p.) on convulsive seizures or on spike discharges (Sp-D) induced by GEt were examined. Several min after the intraventricular injection of 25 μl of GEt solution (300mM), rats started to show myoclonic twitching, running fit and tonic and clonic convulsions. When GEt was injected intraventricularly about 30~40 min after the administration of DZP or PB, rats started to show myoclonic twitching several min after the application of GEt, but rats did not show running fits, tonic convulsions or clonic convulsions for over 4h. EEG (epidural electrodes) revealed initiation of Sp-D several min after an intraventricular injection of GEt (25μl). Thereafter, polyspikes, 3 cps spike & wave complex and finally ictal seizures developed about 30 to 60 min after the injection. EEG revealed Sp-D within 2~10 min on the side of the GEt application on the pia mater (3 μmol), and then a burst of multiple Sp-D developed. During the burst, Sp-D propagated to the opposite cerebral hemisphere. Two hours after the topical application, propagation of Sp-D was completed. In rats given muscimol topically together with GEt, Sp-D were not induced, and Sp-D induced by GEt were suppressed withiin 10 min by the supplimentation of muscimol. While (L-)GABOB and GABA showed a suppressive effet on Sp-D induced by GEt, after pre-application of these two substances, GEt induced Sp-D with longer latency. About 20 min after injection of PB, DZP or PHT, GEt was applied on the pia mater, but Sp-D were not induced. PB, DZP, PHT or VPA, applied 20 min after the application of GEt, suppressed Sp-D induced by GEt. While VPA showed a suppressive effect on Sp-D, GEt induced Sp-D after preapplication of VPA. These findings suggest that GEt acts on the GABAergic system to induce convulsive activity.