Lack of Evidence for a Modulation by Levetiracetam of Metabotropic Glutamate Receptors
Abstract number :
2.005
Submission category :
Year :
2001
Submission ID :
798
Source :
www.aesnet.org
Presentation date :
12/1/2001 12:00:00 AM
Published date :
Dec 1, 2001, 06:00 AM
Authors :
B.A. Lynch, PhD, Cell and Molecular Biology, UCB Research, Inc., Cambridge, MA; A.C. Matagne, MSc, Preclinical CNS Research, UCB SA, Pharma Sector, Braine l[ssquote]Alleud, Belgium; H.V. Klitgaard, PhD, Preclinical CNS Research, UCB SA, Pharma Sector, Bra
RATIONALE: The present study explored whether the mechanism of action of the antiepileptic drug levetiracetam (LEV) involves a modulation of metabotropic glutamate receptors (mGluR). This family of transmembrane proteins has been linked to seizure activity.
METHODS: In vitro experiments used 3H-LEV as a probe to test for binding with the mGluR ligands to a brain-specific binding site for LEV. In vivo experiments evaluated the ability of LEV to counteract behavioral changes induced in mice by intracerebroventricular infusion of the mGluR agonist 1S,3R-ACPD (200 nmol/min).
RESULTS: Neither glutamic acid nor any of the subtype-specific mGluR ligands (S)-AP-4, quisqualic acid, and (2S,3S,4S)-CCG displaced 3H-LEV in crude rat brain membranes. A modest displacement was observed with the non-specific mGluR agonist 1S,3R-ACPD. However, LEV (5.4-170 mg/kg; ip. -60 min) was inactive against face washing and hind limb scratching induced by 1S,3R-ACPD.
CONCLUSIONS: These results suggest that the antiepileptic mechanism of LEV is unrelated to a modulation of mGluRs.
Support: UCB SA
Disclosure: Salary - Lynch -UCB Research, Inc., Matagne -UCB SA, Klitgaard -UCB SA