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Lesogaberan (AZD-3355) hydrochloride is a potent and selective GABAB receptor agonist with an EC50 of 8.6 nM for human recombinant GABAB receptor. The affinity (Kis) of Lesogaberan hydrochloride for rat GABAB and GABAA receptors, as measured by displacement of [3H]GABA binding in brain membranes: 5.1 nM and 1.4 μM, respectively. Lesogaberan hydrochloride inhibits transient lower esophageal sphincter relaxation through a peripheral mode of action[1]. | [in vivo]
Lesogaberan hydrochloride potently stimulates recombinant human GABAB 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) hydrochloride protects human islet β-cells from apoptosis in islet grafts in mice[2].
Lesogaberan (7 μmol/kg) hydrochloride 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: | 48 hours | | Result: | Significantly reduced the percentages of apoptotic islet cells and increased the frequency of insulin+ β-cells in human islet grafts.
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| 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.
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| [References]
[1] Lehmann A, et al. (R)-(3-amino-2-fluoropropyl) phosphinic acid (AZD3355), a novel GABAB receptor agonist, inhibits transient lower esophageal sphincter relaxation through a peripheral mode of action. J Pharmacol Exp Ther. 2009 Nov;331(2):504-12. DOI:10.1124/jpet.109.153593
[2] Tian J, et al. Repurposing Lesogaberan to Promote Human Islet Cell Survival and β-Cell Replication. J Diabetes Res. 2017;2017:6403539. DOI:10.1155/2017/6403539 |
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