Semaglutide (acetate)

Semaglutide is an agonist of glucagon-like peptide 1 receptor (GLP-1R; EC₅₀ = 6.2 pM in a reporter assay using BHK cells expressing the human receptor).¹ It decreases blood glucose levels in the db/db mouse model of type 2 diabetes (ED₅₀ = <2 nmol/kg). Semaglutide (25 nmol/kg) prevents decreases in the number of dopaminergic neurons in the substantia nigra and increases in lipid peroxidation in the substantia nigra and striatum, as well as improves motor coordination in the rotarod and footprint tests in a mouse model of Parkinson's disease induced by MPTP.² It decreases neuronal loss in the hippocampal dentate gyrus and CA1 and CA3 regions and improves motor coordination and grip strength in the beam-walking and hanging wire tests, respectively, in a rat model of stroke induced by permanent middle cerebral artery occlusion (MCAO) when administered at a dose of 10 nmol/kg every other day.³ Formulations containing semaglutide have been used in the treatment of type 2 diabetes.

1.Lau, J., Bloch, P., SchÄffer, L., et al.Discovery of the once-weekly glucagon-like peptide-1 (GLP-1) analogue semaglutideJ. Med. Chem.58(18)7370-7380(2015) 2.Zhang, L., Zhang, L., Li, L., et al.Neuroprotective effects of the novel GLP-1 long acting analogue semaglutide in the MPTP Parkinson's disease mouse modelNeuropeptides7170-80(2018) 3.Yang, X., Feng, P., Zhang, X., et al.The diabetes drug semaglutide reduces infarct size, inflammation, and apoptosis, and normalizes neurogenesis in a rat model of strokeNeuropharmacology158:107748(2019)