The AMPA antagonist ZK 200775 in patients with acute ischaemic stroke: A double-blind, multicentre, placebo-controlled safety and tolerability study

Cerebrovascular Diseases

Volumn 20, Issue 5, 2005, Pages 304-309

  Walters, M R ^a   Kaste, Markku ^b   Lees, K R ^a   Diener, Hans C ^c   Hommel, M ^d   De Keyser, Jacques ^e   Steiner, Heike ^f   Versavel, Mark ^f  

^a WESTERN INFIRMARY   (United Kingdom)

^b HELSINKI UNIVERSITY CENTRAL HOSPITAL   (Finland)

^c UNIVERSITY OF DUISBURG ESSEN   (Germany)

^d HÔPITAL MICHALLON   (France)

^e UNIVERSITY MEDICAL CENTER GRONINGEN   (Netherlands)

^f BAYER PHARMA AG   (Germany)

Author keywords

AMPA antagonist; Blood pressure; Glasgow Coma Scale; NIHSS; Stroke

Indexed keywords

[[3,4 DIHYDRO 7 MORPHOLINO 2,3 DIOXO 6 (TRIFLUOROMETHYL) 1(2H) QUINOXALINYL]METHYL]PHOSPHONIC ACID; AMPA RECEPTOR ANTAGONIST;

ADULT; AGED; ARTICLE; ATAXIA; BRAIN ISCHEMIA; CLINICAL TRIAL; CONFUSION; CONSCIOUSNESS DISORDER; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; DRUG SAFETY; DRUG TOLERABILITY; DYSARTHRIA; FEMALE; HEMODYNAMICS; HUMAN; HYPOTENSION; MAJOR CLINICAL STUDY; MALE; MULTICENTER STUDY; NAUSEA AND VOMITING; NEUROPROTECTION; NYSTAGMUS; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SENSORY DYSFUNCTION; SIDE EFFECT; STROKE; TREATMENT OUTCOME; VISUAL IMPAIRMENT;

ACUTE DISEASE; ADULT; AGED; AGED, 80 AND OVER; BLOOD PRESSURE; BRAIN ISCHEMIA; CEREBROVASCULAR ACCIDENT; ELECTROCARDIOGRAPHY; HUMANS; MIDDLE AGED; PATIENT COMPLIANCE; PHOSPHONIC ACIDS; QUINOXALINES; RECEPTORS, AMPA; TREATMENT OUTCOME;

EID: 27644527749     PISSN: 10159770     EISSN: None     Source Type: Journal    
DOI: 10.1159/000087929     Document Type: Article

References (14)

1. Boast C, Gergardt S, Pastor G: The NMDA antagonists CGS 19755 and CPP reduce ischaemic brain damage in gerbils. Brain Res 1988;442:345-348.
2. Kawasaki-Yatsugi S, Ichiki C, Yatsugi S, Shimizu-Sasamata M, Yamaguchi T: YM90K, an AMPA receptor antagonist, protects against ischaemic damage caused by permanent and transient middle cerebral artery occlusion in rats. Naunyn-Schmiedebergs Arch Pharmacol 1998;358:586-591.
3. Lees GJ: Pharmacology of AMPA/Kainate receptor ligands and their therapeutic potential in neurological and psychiatric disorders. Drugs 2000;59:33-78.
4. Turski L, Huth A, Sheardown M, McDonald F, Neuhaus R, Schneider HH, Dirnagl U, Wiegand F, Jacobsen P, Ottow E: ZK 200775: a phosphonate quinoxalinedione AMPA antagonist for neuroprotection in stroke and trauma. Proc Natl Acad Sci USA 1998;95:10960-10965.
5. Xue D, Huang ZG, Barnes K, Lesiuk HJ, Smith KE, Buchan AM: Delayed treatment with AMPA, but not NMDA, antagonists reduces neocortical infarction. J Cereb Blood Flow Metab 1994;14:251-261.
6. Unpublished Schering Research Report AG99. Explorative investigation of safety, tolerability, pharmacodynamics and pharmacokinetics after infusions of ZK 200775 with increasing doses in older subjects. 1999.
7. Unpublished Schering Research Report AO13. Ophthalmologic examination after a 4-hour infusion with ZK 200775 in elderly healthy male subjects. 1999.
8. Unpublished Schering Research Report AO12. Exploratory investigation of safety, tolerability, and steady-state kinetics after a 24-hour infusion with ZK 200775 in 55- to 65-year-old male volunteers when administered as a loading and subsequent maintenance dose. 1999.
9. Unpublished Schering Research Report AR35. The influence of impaired kidney function on the pharmacokinetics of ZK 200775 after a 4-hour infusion of 10 mg/hour ZK 200775 in male volunteers in the age groups 40 to 59 and 60 to 80 in an open-labeled trial design. 1999.
10. Dyker AG, Edwards KR, Fayad PB, Hormes JT, Lees KR: Safety and tolerability study of aptiganel hydrochloride in patients with an acute ischaemic stroke. Stroke 1999;30:2038-2042.
11. Grotta J, Clark W, Coull B, Pettigrew LC, Mackay B: Safety and tolerability of GCS 19755 (Selfotel) in patients with acute ischaemic stroke: results of a phase IIa randomised trial. Stroke 1995;26:602-605.
12. Unpublished Schering Expert Opinion ad Schering Research Report AO12. Dose-effect relationship simulation of brain concentrations after 24-h infusion of the AMPA antagonist ZK 200775 using EEG parameters within a pharmacokinetic 3-compartment model. 2000.
13. Elting JW, Sulter A, Kaste M, Lees KR, Diener HC, Hommel M, De Keyser J, Teelken AW: The AMPA antagonist ZK 200775 in patients with acute ischaemic stroke: possible glial cell toxicity detected by monitoring of S-100B serum levels. Stroke 2002;33:2813-2818.
14. Walters MR, Bradford APJ, Dyker AG, Lees KR: A phase 1 study of the glutamate antagonist CNS 5161. Stroke 1999;30:P67.