mAChR4 Activator

VU0476406 is a blood-brain barrier-permeable and selective muscarinic acetylcholine receptor subtype 4 (M4) activator with human EC₅₀ of 91.0 nM and human pEC₅₀ of 7.04. VU0476406 potentiates endogenous acetylcholine activity at M4 receptors. VU0476406 can be used for the research of Parkinson's disease.

VU6008055 (AF98943) is a brain-penetrant, orally active and selective muscarinic acetylcholine receptor subtype 4 (mAChR4) activator with human EC₅₀ values of 73.4 nM. VU6008055 potentiates mAChR4 receptor activity in the presence of acetylcholine, and exhibits no activity at mAChR1, mAChR3, or mAChR5. VU6008055 can be used for the research of schizophrenia, parkinson’s disease, alzheimer’s disease.

VU10010 is a potent, highly selective and allosteric M₄ mAChR potentiator with an EC₅₀ of 400 nM. VU10010 binds to an allosteric site on M₄ mAChR and increases affinity for acetylcholine and coupling to G proteins. VU10010 increases carbachol-induced depression of transmission at excitatory but not inhibitory synapses in the hippocampus.

M4 mAChR Modulator-2 is an orally active, selective, brain-penetrant positive allosteric modulator (PAM) of the M4 muscarinic acetylcholine receptor (M4 mAChR) (EC₅₀ = 513 nM). M4 mAChR Modulator-2 exhibits high target selectivity, showing negligible affinity and low inhibition rates for non-target receptors (D1R/D2R/D3R, 5-HT subtypes, κ/δ/μ opioid receptors, H1, M1/M2) while specifically binding to M4 mAChR with a K_i of 377 nM and an inhibition rate of 62.8%. M4 mAChR Modulator-2 reverses Dizocilpine (MK-801) (HY-15084B)-induced hyperlocomotion in mice. M4 mAChR Modulator-2 can be used for the study of schizophrenia