Pentobarbital: Stereospecific actions of (+) and (-) isomers revealed on cultured mammalian neurons

Stereoisomers of the barbiturate anesthetic pentobarbital were applied to mouse spinal neurons growing in tissue culture. Intracellular recordings of neuronal membrane properties revealed that the (+) and (-) isomers caused direct changes in membrane potential and conductance on some but not all of the cells tested. The action of the (+) isomer was predominantly excitatory, whereas the (-) isomer produced predominantly inhibitory responses. The (-) isomer was considerably more effective in potentiating inhibitory responses to the transmitter gamma-aminobutyric acid. The results show that pentobarbital has multiple effects on neuronal excitability and demonstrate the presence of stereospecific sites of barbiturate action on central neurons.