Z944, a Novel Selective T-Type Calcium Channel Antagonist Delays the Progression of Seizures in the Amygdala Kindling Model
Pablo Miguel Casillas-Espinosa, Ashleigh Hicks, Amy Jeffreys, Terrance P Snutch, Terence J O'Brien, Kim L Powell
PLOS ONE | PUBLIC LIBRARY SCIENCE | Published : 2015
Temporal lobe epilepsy (TLE) is the most common form of drug resistant epilepsy. Current treatment is symptomatic, suppressing seizures, but has no disease modifying effect on epileptogenesis. We examined the effects of Z944, a potent T-type calcium channel antagonist, as an anti-seizure agent and against the progression of kindling in the amygdala kindling model of TLE. The anti-seizure efficacy of Z944 (5mg/kg, 10mg/kg, 30mg/kg and 100mg/kg) was assessed in fully kindled rats (5 class V seizures) as compared to vehicle, ethosuximide (ETX, 100mg/kg) and carbamazepine (30mg/kg). Each animal received the seven treatments in a randomised manner. Seizure class and duration elicited by six post-..View full abstract
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Awarded by Canadian Institutes of Health Research
Awarded by NH&MRC Project Grant
Work in the laboratory of Terrance P. Snutch was supported by an operating grant from the Canadian Institutes of Health Research (#10677) and a Canada Research Chair in Biotechnology and Genomics-Neurobiology. Pablo M. Casillas-Espinosa was funded by a Melbourne Research Scholarship. Work for this project was supported in part by a NH&MRC Project Grant to Kim Powell (#628723).