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Implementing a bioassay to screen molecules for antiepileptogenic activity: chronic pilocarpine versus subdudral
Angela Lyon1, Sandra Marone, Dan Wainman
1Department of Chemistry, Queen's University, Kingston, Ont., Canada K7L 3N6.
Background:
There is a need to discover novel chemical compounds that will inhibit the pathological process of epileptogenesis (i.e. agents that will prevent the long-term formation of an active seizure focus following a brain insult). The goal of this paper is to identify a bioassay of value in drug design when screening new chemical entities as putative antiepileptogenic agents.
Methods:
We focused on two models: the pilocarpine chronic seizure model of spontaneous recurrent seizures (SRSs) and a chronic subdural haematoma model of SRSs. Both models were evaluated using more than 20 Sprague-Dawley rats for each model.
Results:
In the pilocarpine-induced model of SRSs, 80% of animals went on to develop SRSs when the dose of pilocarpine was 380 mg/kg i.p. In 50 animals that developed SRSs, the average number of seizures per 15 days of observation was 3.8 seizures with a range of 2-23 seizures per 15-day period. The chronic subdural model was inefficient in producing SRSs.
Conclusions:
A pilocarpine-induced SRS model of epilepsy affords a reliable model of epileptogenesis suitable for evaluating new chemical entities as putative antiepileptogenics.
