Neuroprotective effects of glycine for therapy of acute ischaemic stroke.
The aim of this randomized, double-blind, placebo-controlled trial was to assess the safety and the efficacy of the pharmaceutic drug glycine in 200 patients 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/day and 50 glycine 2.0 g/day for 5 days in each group. The efficacy of glycine was assessed by clinical analysis, by an enzyme-linked immunosorbent assay of levels of blood serum autoantibodies to NMDA-binding proteines, by detection 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 sedation 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 of 1.0-2.0 g/day was accompanied by a tendency to a decreased 30-day mortality (5.9% in 1. 0 g/day glycine and 10% in 2.0 g/day glycine groups vs. 14% in the placebo and 14.3% in 0.5 g/day glycine groups), to an improved clinical outcome on the Orgogozo Stroke Scale (p < 0.01) and the Scandinavian Stroke 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 TBARS 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 started within 6 h after the onset of acute ischaemic stroke in the carotid artery territory is safe and can exert favourable clinical effects. These results will be verified in further trials with a larger number of patients.
Gusev
E I
EI
Department of Neurology and Neurosurgery, Russian State Medical University, Moscow, Russia.
Skvortsova
V I
VI
Dambinova
S A
SA
Raevskiy
K S
KS
Alekseev
A A
AA
Bashkatova
V G
VG
Kovalenko
A V
AV
Kudrin
V S
VS
Yakovleva
E V
EV
D000208:Acute Disease; D000368:Aged; D000596:Amino Acids / Q000134:cerebrospinal fluid; D001323:Autoantibodies / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D005998:Glycine / Q000009:adverse effects / Q000134:cerebrospinal fluid / Q000627:therapeutic use*; D006439:Hemodynamics; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016194:Receptors, N-Methyl-D-Aspartate / Q000097:blood; D020521:Stroke / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000401:mortality; D016896:Treatment Outcome
D000596:Amino Acids; D001323:Autoantibodies; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D005998:Glycine