Kinetics of drug action in disease states. XV: Effect of pregnancy on the convulsive activity of pentylenetetrazol in rats.

The purpose of this investigation was to determine whether the pharmacodynamics of the central nervous system stimulant pentylenetetrazol (1) are altered in advanced pregnancy. Lewis rats that were 20 days pregnant and nonpregnant rats of the same age and strain received either a relatively fast or a relatively slow intravenous infusion of 1 until the onset of a maximal seizure, which occurred after about 11 or 31 min, respectively, of infusion. The concentrations of 1 at that time in serum, cerebrospinal fluid, (CSF) and brain were independent of the infusion rate and did not differ significantly between pregnant and nonpregnant animals. The ratio of concentrations of 1 in the cerebrospinal fluid to that in serum was unity in all groups, consistent with negligible serum protein binding and indicative of rapid penetration of 1 into the central nervous system. It is concluded that advanced pregnancy has no apparent effect on the response of the central nervous system of rats to the convulsive activity of 1.