[Inhibitory effects of L-threo-DOPS on electroshock seizure in mice].
Effects of L-threo-3,4-dihydroxyphenylserine (L-DOPS), a synthetic norepinephrine (NE) precursor, on electroshock seizure were studied in mice. All substances were administered intraperitoneally. Minimal electroshock seizure threshold (EST) was not significantly altered by L-DOPS at a dose of 200 or 400 mg/kg. L-DOPS was unable to abolish tonic extensions of hind legs in maximal electroshock seizure (MES) test at doses from 100 to 400 mg/kg. However, it significantly reduced extension/flexion (E/F) ratio in a dose-dependent manner. Furthermore, L-DOPS dose-dependently blocked maximal electroconvulsions in a combined use with nialamide (30 mg/kg), desipramine (20 mg/kg) or maprotiline (40 mg/kg) at so small doses as not to show any anticonvulsant effect when they were used alone. ED50 (with 95% confidence limit) of L-DOPS in the combination treatments were 210 (145-305), 160 (100-256) and 95 (50-181) mg/kg respectively. Those results indicate that L-DOPS has an anticonvulsant property, which is potentiated by a MAO inhibitor or NE uptake blockers. It was presumed that the effect of L-DOPS was caused by the inhibition of spreading of seizure discharges. It was suggested that L-DOPS would be a useful substance for the investigation on a role of NE in experimental epilepsy and could be used clinically as an adjunct drug for generalized tonic-clonic convulsions.
Yoshida
M
M
Department of Neurology, University of Tsukuba, Ibaraki, Japan.
Nakanishi
T
T
D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D003891:Desipramine / Q000627:therapeutic use; D015103:Droxidopa / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004597:Electroshock; D008297:Male; D008376:Maprotiline / Q000627:therapeutic use; D051379:Mice; D008815:Mice, Inbred Strains; D009526:Nialamide / Q000627:therapeutic use; D012640:Seizures / Q000209:etiology / Q000517:prevention & control*; D012694:Serine
D000927:Anticonvulsants; D008376:Maprotiline; D012694:Serine; D015103:Droxidopa; D009526:Nialamide; D003891:Desipramine