1-(4-METHOXYBENZYL)-4-OXO-1,4-DIHYDRO-3-QUINOLINECARBOXYLIC ACID

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.

BQCA is a potent muscarinic M1 receptor positive allosteric modulator with selectivity for M1 over M2-M5. It potentiates M1 activity in in vitro and in vivo assays and is orally bioavailable. Muscarinic 1 (M1) receptors are expressed in brain regions responsible for attention and memory, including hippocampus, cortex, and striatum. BQCA binds allosterically to M1 to enhance the binding and efficacy of ACh at the receptor. M1 activation is a proposed mechanism for increasing information processing in disease states, such as Alzheimer′s. M1 agonists are being studied as potential therapeutic agents to treat Alzheimer′s disease and the cognitive and negative symptoms of schizophrenia. BQCA has been shown to improve performance in cognition tasks and increase cerebral blood flow.