Inhibitory effects of L-threo-3,4-dihydroxyphenylserine against maximal electroconvulsion and brain norepinephrine in mice

Abstract

L-threo-3,4-dihydroxyphenylserine (L-DOPS) is a synthetic amino acid, which is decarboxylated to form L-norepinephrine in vivo. The effects of L-DOPS on maximal electroshock seizure (MES) were investigated in mice here. All substances were injected intraperitoneally. L-DOPS (100–400 mg/kg) significantly decreased extension/flexion (E/F) ratios, though it could not abolish MES (tonic hind leg extension). However L-DOPS (400 mg/kg) significantly abolished MES, when combined with desipramine (5–20 mg/kg), maprotiline (20–40 mg/kg) or nialamide (30 mg/kg). Similar doses of desipramine, maprotiline, nialamide or L-DOPS could not inhibit MES when used alone.

In the combined treatment with desipramine (20 mg/kg), maprotiline (40 mg/kg) or nialamide (30 mg/kg), the ED₅₀ (95% CL) of L-DOPS for abolition of MES was 160 (100–256), 95 (50–181) or 210 (145–305) mg/kg respectively. The determination of brain NE was made by HPLC. The significant increase of NE was observed in the treatment with L-DOPS, nialamide, or L-DOPS combined with either nialamide, desipramine or maprotiline. Desipramine mildly increased NE, but maprotiline did not alter NE. It was presumed that an anticonvulsant action of L-DOPS and L-DOPS with the combined drugs was due to the modification of brain nonadrenergic transmission.