Table 1.

Studies on the identification of a site where drug concentrations were in direct equilibrium with the target site

	Studies in which CSF concentrations were identified as the compartment ‘pharmacokinetically indistinguishable from the site of action’	Studies in which concentrations in serum, brain and CSF at onset of a defined pharmacologic effect were independent of infusion rate
CNS depressants Pharmacodynamic endpoints  Onset of loss of righting reflex  Offset of loss of righting reflex	Effect of infusion rate on phenobarbital concentrations in serum, brain and cerebrospinal fluid of normal rats at onset of loss of righting reflex [5] Pharmacodynamics of diazepam and its active metabolites in rats [11] Effect of repeated blood sampling on the pharmacodynamics of phenobarbital in rats [91]	Pharmacodynamics of the hypnotic effect of salicylamide in rats [14]a
CNS stimulants Pharmacodynamic endpoints  Onset of seizures (first myoclonic jerk, twitch)  Onset of maximal seizures (tonic flexion of the forelimbs and (usually) tonic extension of the hindlimbs)	Pharmacodynamics of theophylline-induced seizures in rats [15] Chronic theophylline administration has no apparent effect on theophylline concentrations required to produce seizures in rats [92]a	Effect of infusion rate on pentylenetetrazol concentrations in serum, brain and cerebrospinal fluid of rats at onset of convulsions [34]

Most titles in this table are shortened titles. Full titles of the published papers include Kinetics of Drug Action in Disease States, followed by a number (I-XLV), and the short title represented in this table

^aTitles are the full title of the published paper