Lesogaberan

Lesogaberan (AZD-3355) is a potent and selective GABA_B receptor agonist with an EC₅₀ of 8.6 nM for human recombinant GABA_B receptors. The affinity (K_is) of Lesogaberan for rat GABA_B and GABA_A receptors, as measured by displacement of [³H]GABA binding in brain membranes: 5.1 nM and 1.4 μM, respectively. Lesogaberan inhibits transient lower esophageal sphincter relaxation through a peripheral mode of action^[1]. IC50 & Target:Ki: 5.1±1.2 nM (rat GABA_B), 1.4±0.3 μM (rat GABA_A)^[1]
EC50: 8.6±0.77 nM (human GABA_B receptor)^[1] In Vitro: Lesogaberan (3-30 nM) enhances human islet cell proliferation in vitro^[2]. In Vivo: Lesogaberan (AZD3355) potently stimulates recombinant human GABA_B receptors and inhibits transient lower esophageal sphincter relaxation (TLESR) in dogs, with a biphasic dose-response curve^[1].
Oral Lesogaberan (0.08 mg/mL; 48 hours) protects human islet β-cells from apoptosis in islet grafts in mice^[2].
Lesogaberan (7 μmol/kg) shows high oral availability (88% in the dog and 100% in the rat) and relatively low systemic clearance in female SpragueDawley rats^[1].