Neuroscience 2000 Abstract
| Presentation Number: | 662.18 |
|---|---|
| Abstract Title: | The anticonvulsant activity of Δ 9-THC is blocked by pretreatment with the CB1 antagonist, SR141716A. |
| Authors: |
Wallace, M. J.*1
; Martin, B. R.1
; Sombati, S.2
; Woodward, J. J.1
; DeLorenzo, R. J.1,2
1Dept. of Pharmacology & Toxicology, Med. Coll. of VA, VA Commonwealth Univ., Richmond, 2Dept. of Neurology, Med. Coll. of VA, VA Commonwealth Univ., Richmond, |
| Primary Theme and Topics |
J. Disorders of the Nervous System and Aging - 124. Epilepsy: anti-convulsant drugs |
| Secondary Theme and Topics | D. Neurotransmitters, Modulators, Transporters, and Receptors<br />- 54. Cannabinoids |
| Session: |
662. Epilepsy: anticonvulsant drugs Poster |
| Presentation Time: | Wednesday, November 8, 2000 9:00 AM-10:00 AM |
| Location: | Hall G-J |
| Keywords: | Cannabinoids, Maximal Electroshock, Epilepsy |
Epilepsy is a common neurological condition affecting 1% of all Americans. Approximately 30% of epileptic patients are refractory to conventional antiepileptic drug treatments. For these patients, the development of new antiepileptic compounds as primary or adjunct therapies is of great importance. Previous data suggests that cannabinoid and cannabimimetic compounds may be of therapeutic utility in the treatment of epilepsy. In the brain, cannabinoids are thought to work primarily via the CB1 receptor. Activation of cannabinoid receptors has a modulatory effect on many ion channels that influence neuronal action potential spike frequency. In vitro data from our lab and others support the hypothesis that activation of CB1 receptors serves to decrease neuronal excitability. However, there is no evidence that CB1 receptors play a role in the anticonvulsant properties of Δ 9-THC in vivo. Using the Maximal Electroshock Model (MES) of seizure in male CF-1 mice with hind limb tonic extension as the test endpoint, we show that the anticonvulsant properties of Δ 9-THC (ED50 = 42mg/kg) can be blocked by low doses of the CB1 receptor antagonist SR141716A with (AD50 = 1.9mg/kg). These data directly implicate the CB1 receptor as the locus for Δ 9-THC's anticonvulsant properties in vivo. Further investigation of the anticonvulsant properties of the CB1 receptor could lead to novel therapeutic agents for the treatment of refractory seizures.
Supported by <I>RO1-NS23350, PO1-NS25630, P50-DAO5274 and T13-DA07027.</I>
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2000 Neuroscience Meeting Planner. New Orleans, LA: Society for Neuroscience, 2000. Online.
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