Dose escalation study of the NMDA glycine-site antagonist licostinel in acute ischemic stroke

Gregory W. Albers, Wayne Clark, Richard P. Atkinson, Kenneth Madden, Joann L. Data, M. J. Whitehouse

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

Background and Purpose - Licostinel (ACEA 1021; 5-nitro-6,7-dichloro- 2,3-quinoxalinedione), a competitive antagonist of glycine at the N-methyl- D-aspartate (NMDA) receptor, is an effective neuroprotective agent in animal models of cerebral ischemia. The purpose of this study was to assess the safety, tolerability, and pharmacokinetics of licostinel in patients with acute stroke. Methods - In this 5-center dose escalation trial, patients were enrolled within 48 hours of an ischemic stroke and treated with ascending doses of a short infusion of licostinel or a placebo. Adverse effects were assessed with clinical and laboratory measurements, and patient outcome was determined with the National Institutes of Health Stroke Scale. Results - Sixty-four patients (44 treated with escalating doses of licostinel and 20 who received placebo) were treated. Lower doses of licostinel (0.03 to 0.60 mg/kg) were not associated with any significant adverse effects. Higher doses of licostinel (1.2 to 3.0 mg/kg) were associated with a variety of mild-to- moderate adverse effects including neurological and gastrointestinal complaints. No major psychotomimetic effects or significant safety concerns occurred. At the higher dose levels, peak plasma concentrations of licostinel were substantially higher than those required for neuroprotection in animal stroke models. A similar improvement in National Institutes of Health Stroke Scale scores over time was seen in both the placebo group and the licostinel- treated patients. Conclusions - A short infusion of licostinel in doses up to 3.0 mg/kg is safe and tolerable in acute stroke patients. Licostinel may be a safer and better tolerated neuroprotective agent than many of the previously evaluated NMDA antagonists.

Original languageEnglish (US)
Pages (from-to)508-513
Number of pages6
JournalStroke
Volume30
Issue number3
StatePublished - Mar 1999

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N-Methylaspartate
Glycine
Stroke
Placebos
National Institutes of Health (U.S.)
Neuroprotective Agents
licostinel
Animal Models
Safety
N-Methyl-D-Aspartate Receptors
Brain Ischemia
Pharmacokinetics

Keywords

  • Cerebral infarction
  • Neuroprotection
  • Stroke management
  • Stroke, acute

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Neuroscience(all)

Cite this

Albers, G. W., Clark, W., Atkinson, R. P., Madden, K., Data, J. L., & Whitehouse, M. J. (1999). Dose escalation study of the NMDA glycine-site antagonist licostinel in acute ischemic stroke. Stroke, 30(3), 508-513.

Dose escalation study of the NMDA glycine-site antagonist licostinel in acute ischemic stroke. / Albers, Gregory W.; Clark, Wayne; Atkinson, Richard P.; Madden, Kenneth; Data, Joann L.; Whitehouse, M. J.

In: Stroke, Vol. 30, No. 3, 03.1999, p. 508-513.

Research output: Contribution to journalArticle

Albers, GW, Clark, W, Atkinson, RP, Madden, K, Data, JL & Whitehouse, MJ 1999, 'Dose escalation study of the NMDA glycine-site antagonist licostinel in acute ischemic stroke', Stroke, vol. 30, no. 3, pp. 508-513.
Albers GW, Clark W, Atkinson RP, Madden K, Data JL, Whitehouse MJ. Dose escalation study of the NMDA glycine-site antagonist licostinel in acute ischemic stroke. Stroke. 1999 Mar;30(3):508-513.
Albers, Gregory W. ; Clark, Wayne ; Atkinson, Richard P. ; Madden, Kenneth ; Data, Joann L. ; Whitehouse, M. J. / Dose escalation study of the NMDA glycine-site antagonist licostinel in acute ischemic stroke. In: Stroke. 1999 ; Vol. 30, No. 3. pp. 508-513.
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