[The neuroprotective effect of the glutamate antagonist acamprosate following experimental cerebral ischemia. A study with the lipid peroxidase inhibitor u-101033e].

Abstract

INTRODUCTION:

This study investigates the effects of acamprosate, a glutamatergic modulator, and the lipid peroxidation inhibitor U-101033E on neurological outcome following incomplete cerebral ischemia and reperfusion in rats.

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.

• 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)

Chemical References

• Alcohol Deterrents
• Anesthetics, Intravenous
• Enzyme Inhibitors
• Excitatory Amino Acid Antagonists
• Neuroprotective Agents
• Pyrimidines
• Pyrrolidines
• U 101033E
• Taurine
• Peroxidase
• Acamprosate
• Fentanyl

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)