Neurochemical studies with the novel anticonvulsant levetiracetam in mouse brain.
Levetiracetam is a novel antiepileptic agent with a wide spectrum of activity against experimental and clinical seizures. The mechanism of its anticonvulsant action remains to be determined. We have investigated the effects of levetiracetam on several gamma-aminobutyric acid (GABA)-related neurochemical parameters in mouse brain. Adult male mice were randomised into two groups and administered levetiracetam (0-300 mg/kg) intraperitoneally either as a single dose or twice daily for 5 days. Four hours after the final dose, animals were killed and their brains removed. Brain tissues were analysed for concentrations of GABA, glutamate and glutamine and for the activities of GABA-transaminase and glutamic acid decarboxylase. Single dose and repeated levetiracetam treatments were without effect on all of the parameters investigated. The anticonvulsant action of levetiracetam is unlikely to be mediated via an action on the GABAergic system.
Sills
G J
GJ
University Department of Medicine and Therapeutics, Western Infirmary, Glasgow, UK. g.j.sills@clinmed.gla.ac.uk
Leach
J P
JP
Fraser
C M
CM
Forrest
G
G
Patsalos
P N
PN
Brodie
M J
MJ
D000612:4-Aminobutyrate Transaminase / Q000378:metabolism; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D004334:Drug Administration Schedule; D005968:Glutamate Decarboxylase / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D000077287:Levetiracetam; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010889:Piracetam / Q000031:analogs & derivatives* / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000502:physiology
D000927:Anticonvulsants; D005973:Glutamine; D018698:Glutamic Acid; D000077287:Levetiracetam; D005680:gamma-Aminobutyric Acid; D000612:4-Aminobutyrate Transaminase; D005968:Glutamate Decarboxylase; D010889:Piracetam