Relationship between pentylenetetrazol-induced seizures and brain pentylenetetrazol levels in mice.

Pentylenetetrazol (PTZ) is often used in experimental models of epilepsy. The relationship of the PTZ-induced seizure sequence of myoclonus, clonus and hindlimb extension (TE) to brain PTZ levels has not been reported. This study examined this relationship and determined how different routes of PTZ administration affected brain PTZ uptake and seizure development. The critical brain PTZ level for onset of clonus ranged from 20 to 50 microg/g. Brain PTZ uptake was rapid after I.P. injection of PTZ convulsant dose (CD55) for clonus/and clonus onset occured at 4.0+/- 1.6 min. uptake was slower after S.C. administration; clonus onset occurred at 9.9 +/- 3.7 min. at a CD for TE (CD40), clonus onset occured at 5.1 +/- 3.0 and 2.4 +/- 2.4 min for S.C. and I.P. routes of administration, respectively. TE onset did not appear to depend solely on brain PTZ levels were falling . Factors that could modulate the appearance of TE are discussed.