CENTRAL-NERVOUS-SYSTEM UPTAKE KINETICS OF PENTYLENETETRAZOL IN THE DEVELOPING RAT

The present investigation was undertaken to examine the brain uptake kinetics of the central nervous system (CNS) stimulant pentylenetetrazol (PTZ) during postnatal development. This study represents part of an ongoing effort to develop an appropriate seizure model for investigations of anticonvulsant action in the developing rat. The systemic pharmacokinetics of PTZ were examined in male and female adult animals following both intravenous (IV) and subcutaneous (SC) injection. PTZ administered SC was absorbed rapidly and was completely bioavailable in both genders. No statistically significant gender-dependent differences in the disposition of PTZ were identified. To examine the CNS uptake kinetics of PTZ, animals of four different age groups (5, 10, 20, and 60 days postnatal) received timed SC infusions of PTZ. Significant age-related differences in the rate of uptake of PTZ into the CNS were observed. These differences paralleled the previously reported age-dependent changes in the dose of PTZ required to elicit seizure activity. The results of this investigation indicate that the apparent age-related change in sensitivity to the convulsant effects of PTZ is due in part to age-dependent uptake of the convulsant into brain tissue.