Background And Purpose: ZK 200775 is a selective competitive AMPA receptor antagonist. It has demonstrated neuroprotective efficacy in experimental models of stroke and tolerability in healthy volunteers. We tested the safety and tolerability of ZK 200775 in patients with acute ischaemic stroke.
Methods: In a multicentre double-blind, randomised, placebo-controlled phase II trial, 61 ischaemic stroke patients were treated with either placebo or active drug in a dose finding design. Twenty-five patients received placebo, 12 patients received a total dose of 262.5 mg in 48 h (group 1) and 13 patients received a total dose of 525 mg in 48 h (group 2), and 11 patients received a total dose of 105 mg over a period of 6 h (group 3). We studied the pharmacokinetics of the compound and the effect of the infusion on the neurologic and haemodynamic parameters of the patients. The study was not powered to detect neuroprotective efficacy.
Results: In group 2 there was a significant transient worsening in the mean NIH stroke scale score 14- 18 h after the start of treatment. This was due to reduction of consciousness (stupor and coma) in 8 out of 13 patients. Level of consciousness improved approximately 6 h after cessation of infusion. No significant haemodynamic responses were observed. Even after reduction of the administered dose and duration of infusion to 6 h (group 3), 2 patients experienced a reduction in level of consciousness. The effect of ZK 200775 on level of consciousness gave cause for concern and the trial was stopped prematurely for safety reasons.
Conclusions: The AMPA antagonist ZK 200775 reversibly worsened the neurological condition in patients with acute ischaemic stroke. Our results suggest that ZK 200775 exerts significant sedative effects in patients with acute stroke which preclude its further development as a neuroprotective agent in this indication.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1159/000087929 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Aim: To assess the changes of intracranial pressure waveforms (ICPW) acquired noninvasively in a set of acute hydrocephalus patients prior to and posterior to interventions.
Material And Methods: Patients with clinical and radiological diagnoses of hydrocephalus were evaluated for alterations in ICPW by means of a system that detects cranial micro expansions just before and immediately after interventions. The system quantified the difference between ICPW peaks (P1 and P2), providing the P2/P1 ratio.
Toxicity and Quality of Life After Locoregional Radiotherapy in Patients With Thyroid Cancer.
Head Neck
January 2025
Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Background: Locoregional external beam radiotherapy (EBRT) is selectively used in thyroid cancer patients to induce locoregional control. However, despite technological advances, EBRT remains associated with toxicities. We evaluated thyroid-cancer specific toxicities and long-term Quality of Life (QoL) post-EBRT.
View Article and Find Full Text PDFFFR-Negative Nonculprit High-Risk Plaques and Clinical Outcomes in High-Risk Populations: An Individual Patient-Data Pooled Analysis From COMBINE (OCT-FFR) and PECTUS-obs.
Circ Cardiovasc Interv
January 2025
Department of Cardiology, Radboud University Medical Center, Nijmegen, the Netherlands (R.H.J.A.V., J.-Q.M., N.v.R.).
Background: Despite fractional flow reserve (FFR)-guided deferral of revascularization, recurrent events in patients with diabetes or after myocardial infarction remain common. This study aimed to assess the association between FFR-negative but high-risk nonculprit lesions and clinical outcomes.
Methods: This is a patient-level pooled analysis of the prospective natural-history COMBINE (OCT-FFR) study (Optical Coherence Tomography Morphologic and Fractional Flow Reserve Assessment in Diabetes Mellitus Patients) and PECTUS-obs study (Identification of Risk Factors for Acute Coronary Events by OCT After STEMI and NSTEMI Patients With Residual Non- Flow Limiting Lesions).
Intrachromosomal amplification of chromosome 21 (iAMP21) B-cell precursor acute lymphoblastic leukemia (BCP-ALL) in children is a high-risk subtype for which targeted drugs are lacking. In this study, we determined the frequency of secondary lesions in 28 iAMP21 BCP-ALL patient samples and investigated cellular sensitivity for candidate-targeted drugs. iAMP21 was enriched in aberrations (10.
View Article and Find Full Text PDFPrepancreatic postduodenal portal vein discovered in a pediatric patient undergoing total pancreatectomy with islet autotransplantation: a case report and review of literature.
Front Surg
January 2025
Department of Abdominal Transplant and Hepatopancreatobiliary Surgery, Nationwide Children's Hospital, Columbus, OH, United States.
Background: Prepancreatic postduodenal portal vein (PPPV) is a rare anatomic variant where the portal vein (PV) runs anterior to the pancreas and posterior to the duodenum. Only 20 cases of PPPV, all in adults, have been reported in literature. We report the first case of PPPV in a pediatric patient discovered intraoperatively during total pancreatectomy with islet autotransplantation (TPIAT) and the third known case in which the PPPV could be isolated intraoperatively.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!