1‐(3‐(9H‐Carbazol‐9‐yl)‐1‐propyl)‐4‐(2‐methoxyphenyl)‐4‐piperidinol, a novel subtype selective inhibitor of the mouse type II GABA‐transporter

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Abstract
The selectivity of new derivatives of the γ‐aminobutyric acid (GABA)‐uptake inhibitor, tiagabine was characterized at the four cloned mouse GABA transporters (mGAT1 through mGAT4) by measuring [3H]‐GABA uptake into stably transfected baby hamster kidney cells. While tiagabine is a highly selective inhibitor of mGAT1 (Ki=0.11±0.02 μm), these derivatives exhibited low potencies at mGAT1 but differential activities at mGAT2, mGAT3 and mGAT4. In particular, 1‐(3‐(9H‐carbazol‐9‐yl)‐1‐propyl)‐4‐(2‐methoxyphenyl)‐4‐piperidinol (NNC 05‐2090) was a potent inhibitor of mGAT2 (Ki=1.4±0.3 μm) showing at least 10 fold selectivity over mGAT1, mGAT3 and mGAT4. NNC 05‐2090 is the first subtype selective inhibitor of mGAT2 and may represent a novel useful tool for investigating the physiological roles of GAT2 in the brain and periphery.British Journal of Pharmacology (1997) 120, 983–985; doi:10.1038/sj.bjp.0700957