BQCA

BQCA a highly selective allosteric modulator of the M1 mAChR. In Vitro: BQCA reduces the concentration of ACh required to activate M1 up to 129-fold with an inflection point value of 845 nM. No potentiation, agonism, or antagonism activity on other mAChRs is observed up to 100 μM^[1]. BQCA increases M1 receptor affinity for acetylcholine. The activation of the M1 receptor by BQCA induces a robust inward current and increases spontaneous excitatory postsynaptic currents in medial prefrontal cortex (mPFC) pyramidal cells^[2]. In Vivo: BQCA requires M1 to promote inositol phosphate turnover in primary neurons and to increase c-fos and arc RNA expression and ERK phosphorylation in the brain. BQCA reverses scopolamine-induced memory deficits in contextual fear conditioning, increases blood flow to the cerebral cortex, and increases wakefulness while reducing delta sleep. BQCA induces β-arrestin recruitment to M1, suggesting a role for this signal transduction mechanism in the cholinergic modulation of memory^[1]. BQCA increases firing of mPFC pyramidal cells in vivo. BQCA also restores discrimination reversal learning in a transgenic mouse model of Alzheimer's disease^[2].