| Biochem/physiol Actions | VU0029767 is a selective, novel M1 positive allosteric modulator. M1 is a member of the muscarinic acetylcholine family of GPCRs (mAChRs) and is a therapeutic target for cognitive deficits in schizophrenia and Alzheimer's disease. VU0029767 increases both potency and efficacy of acetylcholine (ACh) at M1. VU0029767 also potentiates a mutant M1 receptor, as well as the effects of allosteric agonist TBPB. VU0029767 weakly increases ACh potency at M1 in phospholipase C and phospholipase D assays. This compound was discovered in conjuction with VU0090157 (different chemotype), another M1 modulator, which differs in its activities at the mutant form of M1, potentiation of TBPB, and phospholipase assays. The two modulators differentially regulate G protein signaling following M1 activation. Thus, VU0029767 and VU0090157 are valuable compounds when used together to tease out ligand-directed trafficking. |
