Host: The Japanese Society of Toxicology
There are still many unmet medical needs for disorders of central nervous system (CNS). It’s well known that candidate compounds of new drugs for treatments of CNS disorders have potentials to induce convulsions in human due to their excessive pharmacological effects. Since convulsion is one of life-threatening adverse events in human, it’s essential to fully assess possible convulsion risks of drug candidate compounds before conducting clinical trials.
These days, in vitro convulsion risk evaluation using human iPS cell-derived neurons assay is becoming popular; on the other hand, animal studies will be still necessary to evaluate 1. possible convulsions induced by metabolites, 2. plasma compound concentration at convulsions, and 3. some premonitory signs of convulsions. However, translation of convulsion risk from animals to humans is still a huge challenge because of species differences in susceptibility to drug-induced convulsions.
To solve the issue, we compared convulsion susceptibilities and plasma concentrations at convulsion in mice, rats, and monkeys by using several reference compounds which induced convulsions in humans.
In the symposium, I’ll show details of results in the animal studies and introduce an example of convulsion screening flow prior to clinical trials.
