PHARMACODYNAMICS OF THIOPENTONE - NOCIFENSIVE REFLEX THRESHOLD CHANGES CORRELATE WITH HIPPOCAMPAL ELECTROENCEPHALOGRAPHY

The electroencephalographic (EEG) effects of thiopentone have been use d extensively in the pharmacodynamic and pharmacokinetic modelling of drug effects in the central nervous system (CNS). Thiopentone has a bi phasic (enhancement followed by inhibition) effect on nocifensive refl exes that occurs in a dose range similar to that which activates the E EG. In this study we have used rats chronically instrumented with hipp ocampal EEG (hEEG) electrodes to simultaneously characterize the effec ts of thiopentone on the hEEG and nocifensive reflex thresholds. Enhan cement 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 res ults validate the usefulness of nocifensive reflex thresholds for meas urement of the CNS effects of thiopentone at subanaesthetic concentrat ions.