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GABA A receptors (GABA A Rs) are targets for important classes of clinical agents (e.g., anxiolytics, anticonvulsants, and general anesthetics) that act as positive allosteric modulators (PAMs). Previously, using photoreactive analogs of etomidate ([ 3 H]azietomidate) and mephobarbital [[ 3 H]1-methyl-5-allyl-5-( m -trifluoromethyl-diazirynylphenyl)barbituric acid ([ 3 H] R - m TFD-MPAB)], we identified two homologous but pharmacologically distinct classes of general anesthetic binding sites in the α 1 β 3 γ 2 GABA A R transmembrane domain at β + - α - ( β + sites) and α + - β - / γ + - β - ( β - sites) subunit interfaces. We now use competition photolabeling with [ 3 H]azietomidate and [ 3 H] R-m TFD-MPAB to identify para -substituted propofol analogs and other drugs that bind selectively to intersubunit anesthetic sites. Propofol and 4-chloro-propofol bind with 5-fold selectivity to β + , while derivatives with bulkier lipophilic substitutions [4-( tert -butyl)-propofol and 4-(hydroxyl(phenyl)methyl)-propofol] bind with ∼10-fold higher affinity to β - sites. Similar to R-m TFD-MPAB and propofol, these drugs bind in the presence of GABA with similar affinity to the α + - β - and γ + - β - sites. However, we discovered four compounds that bind with different affinities to the two β - interface sites. Two of these bind with higher affinity to one of the β - sites than to the β + sites. We deduce that 4-benzoyl-propofol binds with >100-fold higher affinity to the γ + - β - site than to the α + - β - or β + - α - sites, whereas loreclezole, an anticonvulsant, binds with 5- and 100-fold higher affinity to the α + - β - site than to the β + and γ + - β - sites. These studies provide a first identification of PAMs that bind selectively to a single intersubunit site in the GABA A R transmembrane domain, a property that may facilitate the development of subtype selective GABA A R PAMs., (Copyright © 2019 by The American Society for Pharmacology and Experimental Therapeutics.)