MOLECULAR ACTIONS OF DROPERIDOL ON HUMAN CNS ION CHANNELS

The molecular effects of droperidol (C22H22FN3O2) on single sodium cha nnels from the human brain were investigated using the electrophysiolo gical planar lipid-bilayer technique. Droperidol (0.05-0.8 mM) induced a concentration dependent and voltage independent reduction in the ti me averaged single channel conductance by two mechanisms: a reduction in the fractional channel open time (major effect, approximately 90%) and a decrease in the channel amplitude (minor effect). The weighted c omputer fit of the concentration response for the combined effect curv e yielded an EC50 of 0.68 mM droperidol and a maximal conductance bloc k of 77%. These blocking effects of droperidol on CNS sodium channels occurred at a concentration range comparable with other specific anaes thetic compounds but far beyond clinical serum levels (up to 0.002 mM) . Therefore in contrast with animal preparations (frog peripheral nerv e, sodium channel) the human brain sodium channel is not a major targe t site for droperidol during clinical anaesthesia.