ABSTRACT
The use of the chemoconvulsant pentylenetetrazol (PTZ) for the discovery of new antiepileptic drugs (AEDs) began in 1944 when G. M. Everett and R. K. Richards demonstrated that trimethadione and phenobarbital, but not phenytoin, could block PTZ-induced seizures. This chapter focuses on the methods employed for conducting both the Subcutaneous (s.c.) and IV PTZ seizure tests, the anatomical substrate for PTZ-induced seizures, the potential advantages and disadvantages of these models as tools for AED discovery, and factors contributing to the interpretation of results obtained. The s.c. PTZ test is a pharmacological model that provides a quantal estimation of a drug’s ability to block a specific seizure endpoint. In addition to PTZ, two other commonly employed chemoconvulsants include bicuculline and Picrotoxin. Efficacy in the Gamma-butyrolactone and s.c. PTZ tests provides a reasonable estimate of the potential efficacy of an investigational AED against generalized absence seizures.
