VU0152099 是一种有效、选择性和可透过血脑屏障的 mAChR M4 正变构调节剂，对大鼠 M4 受体的 EC50 为 0.4 µM。VU0152099 对其他 mAChR 亚型或其他 GPCR 无活性。VU0152099 没有激动剂活性，但增强了 M4 对乙酰胆碱的反应。
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].
[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.
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