Effects of lamotrigine on electrically induced afterdischarge duration in anaesthetised rat, dog, and marmoset.
The effects of lamotrigine (LTG), a novel potent anticonvulsant, following intravenous (i.v.) bolus injection were studied on the durations of electrically induced afterdischarges of the EEG in halothane-anaesthetised dogs and marmosets, species used in toxicity studies. For comparison, the effect of LTG on hippocampal afterdischarge duration was also studied in halothane anaesthetised rats, a species in which the anticonvulsant action of LTG has been widely investigated. The known anticonvulsants phenytoin (PHT) and phenobarbital (PB) were included for comparison. LTG reduced afterdischarge duration in a dose-dependent manner in rat and dog; it was approximately twofold more potent than PHT in the dog and three- to fourfold more potent than PB in both dog and rat (LTG ED50 values = 4.5 and 11.7 mg.kg-1 i.v. in dogs and rats, respectively). PHT was ineffective in the rat at sublethal doses (less than 40 mg.kg-1 i.v.). In limited studies in marmosets, i.v. administration of both LTG and PHT (both 5-15 mg.kg-1) reduced or abolished afterdischarge. Thus, LTG was a potent anticonvulsant in rat, dog, and marmoset in afterdischarge models of partial (focal) seizures and may be of utility in the treatment of partial seizures in humans.
Wheatley
P L
PL
Department of Pharmacology, Wellcome Research Laboratories, Beckenham, Kent, England.
Miller
A A
AA
D000758:Anesthesia; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002143:Callitrichinae / Q000502:physiology*; D004285:Dogs / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D005260:Female; D000077213:Lamotrigine; D008297:Male; D010634:Phenobarbital / Q000494:pharmacology; D010672:Phenytoin / Q000494:pharmacology; D051381:Rats / Q000502:physiology*; D012640:Seizures / Q000503:physiopathology*; D013997:Time Factors; D014227:Triazines / Q000494:pharmacology*
D000927:Anticonvulsants; D014227:Triazines; D010672:Phenytoin; D000077213:Lamotrigine; D010634:Phenobarbital