BQCA is a highly selective positive allosteric modulator of the M1 muscarinic acetylcholine receptor (mAChR), as it dose-dependently reduces the concentration of acetylcholine required to activate the M1 receptor. The effective range for potentiation of M1 in cells by BQCA is 0.1 to 100 μM with an inflection point value of 845 nM when 3 nM acetylcholine is used. BQCA displays no potentiation, agonism, or antagonism at other mAChRs at concentrations up to 100 μM. It has excellent brain penetration and increases the firing rate of medial prefrontal cortex neurons in vivo in rats. BQCA prevents scopolamine-induced memory deficits in both contextual fear conditioning and a spontaneous alternation task in mice. It also restores impairment in reversal learning in a mouse model of Alzheimer’s disease and improves memory performance in rats.
