VU0467154

VU0467154 is a synthetic small-molecule positive allosteric modulator of the M4 subtype of the muscarinic acetylcholine receptor (M4 mAChR), developed as a CNS tool compound to probe M4-mediated modulation of dopaminergic and glutamatergic signaling in neuropsychiatric and neurodegenerative disease models.[8][11][12][18] It binds to an allosteric site on M4 and markedly potentiates the response to endogenous acetylcholine without directly activating the receptor, shifting ACh concentration–response curves and increasing apparent affinity and efficacy at rat, monkey, and human M4 receptors with submicromolar potency and high selectivity over other mAChR subtypes.[8][10][11][12][13][14][18] In rodents, VU0467154 shows good brain penetration and favorable pharmacokinetics after intraperitoneal and oral dosing and exerts antipsychotic-like and cognition-enhancing effects, reversing MK-801- and amphetamine-induced hyperlocomotion, improving associative learning and memory, and normalizing corticostriatal transmission and behavioral deficits in models relevant to schizophrenia, Huntington’s disease, Rett syndrome, and sleep–wake regulation; it is supplied by research reagent vendors for in vitro and in vivo preclinical studies and is not developed for therapeutic use in humans.[1][6][8][10][12][14][16][18]

Other names

5-amino-3,4-dimethyl-N-[[4-(trifluoromethyl)sulfonyl)phenyl]methyl]thieno[2,3-c]pyridazine-6-carboxamide5-amino-3,4-dimethyl-N-(4-((trifluoromethyl)sulfonyl)benzyl)thieno[2,3-c]pyridazine-6-carboxamide