| Abstract | Status epilepticus is a serious neurological disorder associated with a significant morbidity and mortality. Antiepileptic drugs such as diazepam, phenobarbital and phenytoin are the mainstay of status epilepticus treatment. However, over 20% of status epilepticus cases are refractory to the initial treatment with two or more antiepileptic drugs. Endocannabinoids have been implicated as playing an important role in regulating seizure activity and seizure termination. This study evaluated the effects of the major endocannabinoids methanandamide and 2-arachidonylglycerol (2-AG) on status epilepticus in the low-Mg(2+) hippocampal neuronal culture model. Status epilepticus in this model was resistant to treatment with phenobarbital and phenytoin. Methanandamide and 2-AG inhibited status epilepticus in a dose-dependent manner with an EC(50) of 145+/-4.15 nM and 1.68+/-0.19 microM, respectively. In addition, the anti-status epilepticus effects of methanandamide and 2-AG were mediated by activation of the cannabinoid CB(1) receptor since they were blocked by the cannabinoid CB(1) receptor antagonist AM251. These results provide the first evidence that the endocannabinoids, methanandamide and 2-AG, are effective inhibitors of refractory status epilepticus in the hippocampal neuronal culture model and indicate that regulating the endocannabinoid system may provide a novel therapeutic approach for treating refractory status epilepticus. |
| Authors | Laxmikant S Deshpande, Robert E Blair, Julie M Ziobro, Sompong Sombati, Billy R Martin, Robert J DeLorenzo
(Affiliation: Department of Neurology, Virginia Commonwealth University, Richmond, VA 23298, USA.)
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| Journal | European journal of pharmacology
(Eur J Pharmacol)
Vol. 558
Issue 1-3
Pg. 52-9
(Mar 8 2007)
ISSN: 0014-2999 Netherlands |
| PMID | 17174949
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- Anticonvulsants
- Arachidonic Acids
- Endocannabinoids
- Glycerides
- Receptor, Cannabinoid, CB1
- methanandamide
- 2-arachidonylglycerol
- Magnesium
|
| Topics |
- Animals
- Anticonvulsants
(pharmacology)
- Arachidonic Acids
(pharmacology)
- Cells, Cultured
- Endocannabinoids
(pharmacology)
- Glycerides
(pharmacology)
- Hippocampus
(drug effects)
- Magnesium
(pharmacology)
- Rats
- Rats, Sprague-Dawley
- Receptor, Cannabinoid, CB1
(drug effects, physiology)
- Status Epilepticus
(prevention & control)
|
