Given the heterogeneity within the GABA receptor and transporter families, the detailed insight into the pharmacology is still relatively sparse. To enable studies of the physiological roles governed by specific receptor and transporter subtypes, a series of GABA analogs comprising five-membered nitrogen- and sulfur-containing heterocycles as amine bioisosteres were synthesized and pharmacologically characterized at native and selected recombinant GABA_A receptors and GABA transporters. The dihydrothiazole and imidazoline analogs, 5-7, displayed moderate GAT activities and GABA_A receptor binding affinities in the mid- to high-nanomolar range (K_i 90-450 nM). Moreover, they exhibited full and equipotent agonist activity compared to GABA at GABA_A-αβγ receptors but somewhat lower potency as partial agonists at the GABA_A-ρ1 receptor. Stereoselectivity was observed for compounds 4 and 7 for the GABA_A-αβγ receptors but not the GABA_A-ρ1 receptor. The methylated analogs 8-10 displayed negligible GAT activity and reduced agonist activity on all GABA_A-αβγ subtypes, whereas cis-8, 9, and u-10 were found to be weak GABA-ρ antagonists, which could be rationalized by the receptor models. This study illustrates how subtle structural differences in these novel amino GABA bioisosteres can result in diverse pharmacological profiles in terms of selectivity and efficacy.