Abstract | INTRODUCTION: MATERIAL AND METHODS: Twenty-seven male Sprague-Dawley rats were randomly assigned to one of the following treatment groups: 1 (n = 9, control, no drug treatment), 2 (n = 9, 2 x 200 mg/kg acamprosate i.p.), and 3 (n = 9, 2 x 0.3 mg/kg U-101033E i.v.). Background anesthesia was maintained using a combination of fentanyl and O2/N2O (FiO2 = 0.3). Ischemia was produced by combined unilateral common carotid artery ligation and hemorrhagic hypotension to a mean arterial blood pressure (MAP) of 35 mm Hg for 30 minutes. Functional neurological deficit was evaluated for the following 3 days after cerebral ischemia. RESULTS: At the third postischemic day, five control animals and five animals treated with U-101033E were dead for stroke-related reasons. Surviving animals presented severe neurological deficits. In contrast, acamprosate improved neurological outcome, with stroke-related death occurring in one animal only and a minor neurological deficit in the surviving rats. DISCUSSION: The present study demonstrates that acamprosate, in contrast to U-101033E, significantly reduces neurological deficits following transient hemispheric ischemia. The neuroprotective mechanisms of acamprosate may be related to its antiglutamatergic effect with consecutive reduction of transmembraneous Ca++ flux through NMDA-activated ion channels.
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Authors | K Engelhard, C Werner, H Lu, O Möllenberg, W Zieglgänsberger, E Kochs |
Journal | Der Anaesthesist
(Anaesthesist)
Vol. 49
Issue 9
Pg. 816-21
(Sep 2000)
ISSN: 0003-2417 [Print] Germany |
Vernacular Title | Der neuroprotektive Einfluss des Glutamat-Antagonisten Acamprosat nach experimenteller zerebraler Ischämie. Ein Vergleich mit dem Lipidperoxidase-Inhibitor U-101033E. |
PMID | 11076270
(Publication Type: Journal Article)
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Chemical References |
- Alcohol Deterrents
- Anesthetics, Intravenous
- Enzyme Inhibitors
- Excitatory Amino Acid Antagonists
- Neuroprotective Agents
- Pyrimidines
- Pyrrolidines
- U 101033E
- Taurine
- Peroxidase
- Acamprosate
- Fentanyl
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Topics |
- Acamprosate
- Alcohol Deterrents
(pharmacology)
- Anesthetics, Intravenous
(toxicity)
- Animals
- Brain Ischemia
(pathology)
- Enzyme Inhibitors
(pharmacology)
- Excitatory Amino Acid Antagonists
(pharmacology)
- Fentanyl
(toxicity)
- Lipid Peroxidation
(drug effects)
- Male
- Neuroprotective Agents
(pharmacology)
- Peroxidase
(antagonists & inhibitors)
- Pyrimidines
(pharmacology)
- Pyrrolidines
(pharmacology)
- Rats
- Rats, Sprague-Dawley
- Taurine
(analogs & derivatives, pharmacology)
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