3-amino-N-(1,3-benzodioxol-5-ylmethyl)-4,6-dimethylthieno[2,3-b]pyridine-2-carboxamide

Biological Activity

VU0152099 is a potent, selective and brain-penetrant mAChR M4 positive allosteric modulator with an EC50 of 0.4 μM for rat M4 receptor. VU0152099 is inactive for other mAChR subtypes or other GPCRs. VU0152099 has no agonist activity but potentiated responses of M4 to acetylcholine[1]. VU0152099 (30 μM) induces a dose-dependent leftward shift of the acetylcholine (ACh) concentration response curve (CRC) with maximal shifts of 30-fold observed with 30 μM. VU0152099 dose-dependently potentiates the response to an EC20 concentration of ACh with EC50 values of 1.2 μM, and increases the maximal response to ACh to approximately 130%. VU0152099 is a potent positive allosteric modulator that enhance the response of the M4 receptor to the endogenous agonist ACh[1]. VU0152099 (56.6 mg/kg; i.p.; once) reverses Amphetamine-induced hyperlocomotion in rats[1].

References

[1]. Ashley E Brady, et al. Centrally active allosteric potentiators of the M4 muscarinic acetylcholine receptor reverse amphetamine-induced hyperlocomotor activity in rats. J Pharmacol Exp Ther. 2008 Dec;327(3):941-53.