VU6007678

VU6007678 (compound 18g) is an enhancer of muscarinic acetylcholine receptors (mAChR) capable of penetrating the central nervous system. It amplifies acetylcholine-mediated signaling in human M1, M3, and M5, as well as rat M1, M3, M4, and M5 muscarinic acetylcholine receptors. VU6007678 is applicable in research related to Alzheimer's disease, schizophrenia, and ischemic stroke.

VU6007678, starting from a 30 μM concentration and diluted in a tenfold serial manner, incubated with cells for 2.5 minutes and co-incubated with EC 20 acetylcholine for 1 minute, is a potent positive allosteric modulator targeting the human M5 receptor expressed in CHO cells, with an EC₅₀ of 41 nM and a maximal response reaching 74% of acetylcholine's peak activity. This compound acts similarly on the rat M5 receptor with an EC₅₀ of 74 nM and a maximal response of 76%. For the human M1 receptor, also expressed in CHO cells, VU6007678 exhibits an EC₅₀ of 1034 nM with a maximal response of 67%, while demonstrating an EC₅₀ of 466 nM and a maximal response of 71% for the human M3 receptor. It serves as a positive allosteric modulator for the rat M1 receptor with an EC₅₀ of 904 nM and a maximal response of 69%, and for the rat M3 receptor, it shows an EC₅₀ of 772 nM with a 51% maximal response. Additionally, the compound acts as a weak positive allosteric modulator for the rat M4 receptor, with an EC₅₀ of 3913 nM and a maximal response of 49% of acetylcholine's peak activity.