Effects of Oleamide on Tetrodotoxin-sensitive Sodium Channels Investigated.Nicholson et al.(page 120)

Originally detected in the cerebral spinal fluid of sleep-deprived cats, oleamide (cis -9,10-octadecenoamide; cOA) has been found to induce sleep when injected into rats, but its cellular actions are not well-understood. Using standard binding and electrophysiologic protocols, Nicholson et al.  sought to characterize the effects of the sleep-inducing lipid on voltage-gated sodium channels in mouse brain and neuroblastoma cells. Murine neuroblastoma cells were incubated at 37°C in 5% CO2; for some of the experiments, 2% dimethyl sulfoxide was added to the growth medium, increasing Na+current density in the clamped somata without altering oleamide sensitivity. Cells were selected for electrophysiologic experiments 24–36 h after plating. cOA stereoselectively inhibited specific binding of batrachotoxin (scorpion venom) to voltage-gated sodium channels. cOA blocked tetrodotoxin-sensitive sodium currents (maximal effect and affinity were significantly greater at depolarized potentials). Between 3.2 and 64 μm, the block was concentration dependent and saturable, but cOA did not alter the voltage at which one half maximal conductance occurred for activation curves or measured reversal potential.

The experiments showed that oleamide has the capacity to exert concurrently inhibitory effects on presynaptic Na+channels and postsynaptic γ-aminobutyric acid type A receptors. The results suggest that this hypnogenic isomer has a similar molecular mode of action to other drugs that are widely used for the treatment of anxiety, sleep disorders, and epilepsy. cOA may represent an endogenous ligand for depressant drug sites in the mammalian brain.