Lesogaberan (AZD-3355) napadisylate is a potent and selective agonist of GABA B receptors, with an EC50 of 8.6 nM for human recombinant GABA B receptors. It has an affinity (Ki) of 5.1 nM for rat GABA B receptors and 1.4 μM for GABA A receptors, determined by displacement of [3H]GABA binding in brain membranes. 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 at concentrations of 3-30 nM effectively promotes the proliferation of human islet cells in vitro[2]. Specifically, treatment with Lesogaberan at 3 nM resulted in a marginal, yet statistically insignificant, proliferative effect. Conversely, higher concentrations (10 and 30 nM) significantly enhanced cell proliferation by 2-3 times compared to islets grown in the absence of the compound, as observed over a 4-day incubation period[2].

Lesogaberan (AZD3355) effectively stimulates human GABA B receptors and reduces transient lower esophageal sphincter relaxation (TLESR) in canine models, demonstrating a biphasic dose-response relationship. Additionally, oral administration of Lesogaberan (0.08 mg/mL for 48 hours) has been shown to protect human islet β-cells from apoptosis in mouse islet grafts. The compound exhibits high oral bioavailability (88% in dogs and 100% in rats) and low systemic clearance in female Sprague Dawley rats, with only 1% plasma protein binding observed in both rat and human plasma. Experimental results include significant reduction in apoptotic cells and increase in insulin-positive β-cells within human islet grafts in diabetic NOD/scid mice following oral administration.