Biochem/physiol Actions
Orally active, CNS-penetrant, muscarinic acetylcholine receptor M1-selective positive allosteric modulator (PAM) without agonist activity or adverse cholinergic toxicity.
VU0486846 is an orally active, CNS-penetrant and highly selective muscarinic acetylcholine receptor M1 positive allosteric modulator (PAM) with little agonist activity (rat M1 EC50 = 230 nM, 93% ACh max; agonist EC50 > 10 μM) or adverse cholinergic toxicity. VU0486846 improves pathology and cognitive deficits in female APPswe/PSEN1ΔE9 mice (10 mg/day via drinking water), as well as enhances recognition memory and reverses 3 mg/kg risperidone-induced deficits in acquisition of contextual fear conditioning in rats in vivo (3-10 mg/kg i.p.).