Sensitivity to anesthesia by pregnanolone appears late in evolution.

The anesthetic effect of certain steroids in vertebrate systems is well documented, but it is not known if these compounds can cause anesthesia in simpler organisms. To answer this question, ether, short-chain alkanols, and pregnanolone were tested for their ability to induce anesthesia in 20 aquatic species from 7 phyla. Organisms were placed in water containing clinical concentrations of anesthetic. Loss of righting reflex and escape response were used as indicators of anesthesia. All organisms tested responded to ether and short-chain alkanols, but pregnanolone affected only organisms belonging to the phylum Chordata. It is probable that pregnanolone exerts its effect on the gamma amino butyric acid (GABA) receptor, and many invertebrates do possess GABA receptors. These results suggest that a steroid anesthetic binding site appeared early in chordate evolution on a previously existing GABA receptor. Further, this experiment appears to exclude lipid bilayer sites for steroid anesthetic action.