VU 0255035

VU0255035 is a highly selective and competitive M1 mAChR antagonist. VU0255035 blocks M1 mAChR signals to reduce epileptic seizures and regulate neuronal membrane potential. VU0255035 can be used in research related to central nervous system diseases, such as epilepsy, Parkinson's disease, and dystonia^[1][2][3]. In Vitro:VU0255035 (0.1-3 μM) parallels the rightward shift of the concentration-response relationship of acetylcholine (ACh)-induced calcium mobilization and interacts with the orthosteric binding site of ACh as a competitive antagonist^[1].
VU0255035 (1 nM-0.1 μM; 75 min) concentration-dependently blocks carbachol (CCh)-induced phosphatidylinositol (PI) hydrolysis in rat hippocampal slices with an IC₅₀ of 2.4 μM^[1].
VU0255035 (5 μM) completely blocks CCh-induced enhancement of NMDAR currents in hippocampal CA1 pyramidal neurons^[1].
VU0255035 (5 μM) can significantly reduce the amplitude of choline-induced long-term depression (LTD) in hippocampal slice electrophysiological experiments, proving that choline-induced LTD depends on M? receptors^[2].
VU0255035 (5 μM) can completely block CCh-induced membrane potential depolarization of pyramidal neurons in the medial prefrontal cortex (mPFC) in brain slice membrane potential recording experiments^[3].
In Vivo:VU0255035 (10 mg/kg; ip; single dose) antagonizes the M1 muscarinic acetylcholine receptor (mAChR) in vivo in a mouse epilepsy model induced by Pilocarpine (HY-B0726A), significantly reducing seizure scores and 24-hour mortality, and alleviating epileptic symptoms^[1].
VU0255035 (3-30 mg/kg; ip; single dose) has no effect on the acquisition of contextual fear conditioning in a rat contextual fear conditioning model, similar to M1 mAChR knockout mice. VU0255035 may not cause severe cognitive deficits like non-selective anticholinergic drugs^[1].