Pharmacodynamics of thiopentone: nocifensive reflex threshold changes correlate with hippocampal electroencephalography

The electroencephalographic (EEG) effects of thiopentone have been used extensively in the pharmacodynamic and pharmacokinetic modelling of drug effects in the central nervous system (CNS). Thiopentone has a biphasic (enhancement followed by inhibition) effect on nocifensive reflexes that occurs in a dose range similar to that which activates the EEG. In this study we have used rats chronically instrumented with hippocampal EEG (hEEG) electrodes to simultaneously characterize the effects of thiopentone on the hEEG and nocifensive reflex thresholds. Enhancement of these two measures of CNS effect correlated well with plasma thiopentone concentrations of 10-30 mu g ml(-1) (35-75 mu mol litre(-1)) but maximal reflex enhancement occurred at concentrations of 3 mu g ml(-1) (11 mu mol litre(-1)) less than the peak hEEG effect. The results validate the usefulness of nocifensive reflex thresholds for measurement of the CNS effects of thiopentone at subanaesthetic concentrations.