Journal
EPILEPSY RESEARCH
Volume 59, Issue 1, Pages 43-50Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.eplepsyres.2004.03.004
Keywords
status epilepticus; NMDA receptor; hippocampus; CPP; ifenprodil MK-801
Categories
Funding
- NIGMS NIH HHS [T32 GM008136] Funding Source: Medline
- NINDS NIH HHS [R01 NS 40337, R01 NS040337, R01 NS044370-02, R01 NS044370, K02 NS 02081, R01 NS040337-04A2] Funding Source: Medline
Ask authors/readers for more resources
Three different classes of NMDA receptor antagonists were compared for their effectiveness in terminating prolonged status epilepticus (SE), induced by continuous hippocampal stimulation. Animals were treated after 150 min of SE by intraperitoneal administration of increasing doses of 3-((R,S)-2-carboxypiperazin-4-yl)-propyl-l-phosphonic acid (CPP), MK-801 (dizocilpine), ifenprodil, or saline. EEG recordings were used to determine seizure termination. The first experiment (n = 57 animals) determined the most effective anticonvulsant dose of each agent by determining its ability to terminate SE within the next 300 min. Five control rats treated with normal saline after 150 min of SE continued to exhibit continuous seizures for the next 300 min. All drugs were administered after 150 min of SE. CPP terminated seizures with an ED50 of 6.4 mg/kg; the maximal effective dose was 15 mg/kg. MK-801 has an ED50 of 1.4 mg/kg; the maximal effective dose was 2 mg/kg. Ifenprodil was maximally effective at 30 mg/kg. However, an ED50 could not be calculated. In a subsequent experiment, the NMDA antagonists were compared for their ability to terminate prolonged SE within 60min of their administration at the most effective dose. MK-801 (2.0 mg/kg) terminated SE in 6 of 10 animals within 60 min, CPP (15 mg/kg) terminated it in 1 of 9 animals; ifenprodil (30 mg/kg) did not terminate it in any of 9 animals treated. In the 300 min following administration, CPP (6/9) and MK-801 (6/10) were equally efficacious in terminating SE but ifenprodil (2/7) was less effective (P = 0.065, chi-square test). The results indicate that the non-competitive NMDA receptor antagonist MK-801 was superior to the competitive antagonist CPP and the pH-sensitive site antagonist ifenprodil, in terminating prolonged experimental SE. (C) 2004 Published by Elsevier B.V.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available