Lesogaberan (AZD-3355) napadisylate is a potent and selective agonist of GABA B receptors, with an EC 50 of 8.6 nM for human recombinant GABA B receptors. It demonstrates an affinity (Ki) of 5.1 nM for rat GABA B receptors and 1.4 μM for GABA A receptors, as determined by its displacement of [3H]GABA binding in brain membranes. Notably, Lesogaberan napadisylate exerts a peripheral mode of action, inhibiting transient lower esophageal sphincter relaxation.

GABAA (rat):1.4±0.3 μM (Ki), GABAB (rat):5.1±1.2 nM (Ki), GABAB receptor (human):8.6±0.77 nM (EC50)

Lesogaberan (3-30 nM) enhances human islet cell proliferation in vitro[2]. Cell Proliferation Assay[2]Cell Line: Human islet cells Concentration: 3, 10, and 30 nM Incubation Time: 4 days Result: Had a small but nonsignificant promitotic effect at 3?nM, while treatment at higher dosages (10 and 30?nM) led to a 2-3-fold increase in proliferation relative to that of islets cultured in medium alone.

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]. Animal Model: Diabetic NOD/scid mice were implanted with human islets[2]Dosage: 0.08?mg/mL Administration: Oral feeding; 48 hours Result: Significantly reduced the percentages of apoptotic islet cells and increased the frequency of insulin + β-cells in human islet grafts. Animal Model: Female Sprague Dawley rats[1]Dosage: 7 μmol/kg (Pharmacokinetic Analysis) Administration: Oral Result: High oral availability (88% in the dog and 100% in the rat) and relatively low systemic clearance. Plasma protein binding was 1% in rat and human plasma.