BQCA (benzylquinolone carboxylic acid) a highly selective allosteric M1 mAChR modulator.

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.

BQCA induces β-arrestin recruitment to M1, suggesting a role for this signal transduction mechanism in the cholinergic modulation of memory. 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 increases firing of mPFC pyramidal cells in vivo. BQCA also restores discrimination reversal learning in a transgenic mouse model of Alzheimer's disease.

Competition binding reactions used 25 μg human M1 CHO membrane protein, BQCA or vehicle, and 0.15 nM [3H]NMS in 96-well deep-well plates. Binding reactions (30 °C for 2-3 h) are terminated by rapid filtration. Nonspecific binding is determined by adding 10 μM atropine. Filter plates are ished 4×with ice-cold 20 mM HEPES, 100 mM NaCl, and 5 mM MgCl2, pH 7.4 using a 96-well harvester. Plates are dried and radioactivity counted with a microplate scintillation counter[1].