Neuroprotective effects of glycine for therapy of acute ischaemic stroke

The aim of this randomized, double-blind, placebo-controlled trial was to a ssess the safety and the efficacy of the pharmaceutic drug glycine in 200 p atients with acute! (<6 h) ischaemic stroke in the carotid artery territory . Fifty patients received placebo, 49 glycine 0.5 g/day, 51 glycine 1.0 g/d ay and 50 glycine 2.0 g/day for 5 days in each group. The efficacy of glyci ne was assessed by clinical analysis, by an enzyme-linked immunosorbent ass ay of levels of blood serum autoantibodies to NMDA-binding proteines, by de tection of excitatory (glutamate, aspartate) and inhibitory (glycine, GABA) amino acid concentrations and lipid peroxidation products (TBARS) in CSF. The trial confirmed the safety profile of the glycine treatment. Slight sed ation was observed in 9 patients (4.5%) as a side-effect. Other marked side -effects or adverse events were absent. The glycine treatment at the dose o f 1.0-2.0 g/day was accompanied by a tendency to a decreased 30-day mortali ty (5.9% in 1.0 g/day glycine and 10% in 2.0 g/day glycine groups vs. 14% i n the placebo and 14.3% in 0.5 g/day glycine groups), to an improved clinic al outcome on the Orgogozo Stroke Scale (p < 0.01) and the Scandinavian Str oke Scale (p < 0.01) and to a favourable functional outcome on the Barthel index (p < 0.01 in 1.0 g/day glycine vs. placebo group in patients with no or mild disability). An early normalization of autoantibody titres to NMDA- binding proteins in serum was found (p < 0.01 vs. placebo), a reduction of glutamate and aspartate levels (p < 0.05 vs. placebo), an increase in GABA concentrations (p < 0.01 vs. placebo in severe stroke patients) and also a reduction of TEARS levels (p < 0.05 vs. placebo) in CSF by day 3. Thus, the trial suggests that sublingual application of 1.0-2.0 g/day glycine starte d within 6 h after the onset of acute ischaemic stroke in the carotid arter y territory is safe and can exert favourable clinical effects. These result s will be verified in further trials with a larger number of patients. Copy right (C) 2000 S. Karger AG, Basel.