VU0467154

VU0467154 is a positive allosteric modulator of the M4 muscarinic acetylcholine receptor that potentiates acetylcholine responses in CHO cells expressing M4 receptors (EC50s = 17.7, 630, and 1,000 nM for rat, human, and cynomolgus monkey receptors, respectively). It is selective for M4 over M1-3 and M5 receptors and a panel of receptors, transporters, and cation channels when used at a concentration of 10 µM. In vivo, VU0467154 (3-56.6 mg/kg, p.o.) reverses amphetamine-induced hyperlocomotion in rats. It reverses MK-801-induced hyperlocomotion, deficits in a pairwise visual discrimination task, and impairments in the acquisition of contextual fear conditioning in wild-type, but not M4 knockout, mice. VU0467154 (3-30 mg/kg) also increases freezing behavior in contextual and tone fear conditioning tests in wild-type mice when administered prior to the conditioning session. Chronic administration of VU0467154 (10 mg/kg once daily) reduces motor incoordination and prevents decreases in locomotion in the YAC128 transgenic mouse model of Huntington's disease.Formal Name: 5-amino-3,4-dimethyl-N-[[4-[(trifluoromethyl)sulfonyl]phenyl]methyl]-thieno[2,3-c]pyridazine-6-carboxamide. CAS Number: 1451993-15-9. Molecular Formula: C17H15F3N4O3S2. Formula Weight: 444.5. Purity: >95%. Formulation: (Request formulation change), A solid. Solubility: DMSO: Soluble. SMILES: CC1=NN=C2C(C(N)=C(C(NCC3=CC=C(S(=O)(C(F)(F)F)=O)C=C3)=O)S2)=C1C. InChi Code: InChI=1S/C17H15F3N4O3S2/c1-8-9(2)23-24-16-12(8)13(21)14(28-16)15(25)22-7-10-3-5-11(6-4-10)29(26,27)17(18,19)20/h3-6H,7,21H2,1-2H3,(H,22,25). InChi Key: UDSFKIFLJPECRN-UHFFFAOYSA-N.