Drugs Target Epileptic Absence Seizures

Two rationally designed drugs effectively treat a form of epilepsy known as absence seizures in rats with a genetic predisposition to the disorder (Sci. Transl. Med., DOI: 10.1126/scitranslmed.3003120). During absence seizures, which are most common in children and adolescents, a person momentarily loses awareness and is unresponsive. Current absence seizure drugs act on broad ranges of targets, and they cause a host of side effects. Absence seizures stem from the concerted over-firing of neurons in the thalamus. Recent evidence suggests that a subset of Ca²⁺ channels, known as T-type, in the neurons act as conduits to propagate this hyperactive firing. Terrance P. Snutch of the University of British Columbia, Elizabeth Tringham of pharmaceutical firm Zalicus, and colleagues started their design with an N-type Ca²⁺ channel-blocking pharmacophore. They assembled compound libraries, finding two molecules designated Z941 and Z944 that block T-type Ca²⁺ channels in thalamus neurons. They tested the compounds on epileptic rats, showing that the drugs suppressed absence seizures by 85 to 90%. The researchers say the drugs’ action appears to be different from that of current absence seizure drugs.