Conventional anticonvulsant drugs in the guinea-pig kindling model of partial seizures: effects of acute carbamazepine.
This study addressed the anticonvulsant effect of carbamazepine (CBZ) in the guinea-pig kindling model to further test this model for the screening of anticonvulsant drugs. We analysed plasma concentrations of CBZ at various time intervals after intraperitoneal injection of either 10, 25 or 40 mg/kg CBZ. Behavioural toxicity was assessed at 0.5 h postinjection using quantitative locomotor tests, as well as scores on a sedation/muscle relaxation rating index. The anticonvulsant efficacy of CBZ was evaluated from measurements of afterdischarge threshold (ADT), afterdischarge duration (ADD), and behavioural seizure severity at three phases of kindling: non-kindled, kindling acquisition (early and late) and kindled (50+ ADs). ADD and seizure severity were also measured in response to both threshold and suprathreshold kindling stimulation. Plasma levels of CBZ were within, or higher, than the human therapeutic range at the time of behavioural testing and kindling. CBZ exerted slight effects in guinea-pigs on the sedation rating index but not the behavioural tests. CBZ increased ADT and reduced ADD and seizure severity throughout all phases of kindling, indicating that the guinea-pig model correctly predicts CBZ's anticonvulsant effect. CBZ in the guinea-pig kindling model produced consistent anticonvulsant activity that did not appear to be dependent on stimulation intensity.
Gilbert
T H
TH
Behavioural Neuroscience Research Group, Department of Psychology, University of Calgary, 2500 University Drive, NW, Calgary, Alberta, T2N 1N4, Canada.
Teskey
G C
GC
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000927:Anticonvulsants / Q000097:blood / Q000378:metabolism* / Q000633:toxicity; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D002220:Carbamazepine / Q000097:blood / Q000378:metabolism* / Q000633:toxicity; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004558:Electric Stimulation / Q000009:adverse effects; D005260:Female; D006168:Guinea Pigs / Q000378:metabolism*; D007696:Kindling, Neurologic / Q000187:drug effects* / Q000502:physiology; D008297:Male; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D012640:Seizures / Q000188:drug therapy* / Q000503:physiopathology
D000927:Anticonvulsants; D002220:Carbamazepine