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.