M1受体的正构构调节剂;Positive allosteric modulator of M1receptors;BQCA a highly selective allosteric modulator of the M1 mAChR.;BQCA a highly selective allosteric modulator of the M1 mAChR.
体内研究:
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. BQCA increases firing of mPFC pyramidal cells in vivo. BQCA also restores discrimination reversal learning in a transgenic mouse model of Alzheimer's disease.
参考文献:
1. Ma L, et al. Selective activation of the M1 muscarinic acetylcholine receptor achieved by allosteric potentiation. Proc Natl Acad Sci U S A. 2009 Sep 15;106(37):15950-5. 2. Shirey JK, et al. A selective allosteric potentiator of the M1 muscarinic acetylcholine receptorincreases activity of medial prefrontal cortical neurons and restores impairments in reversal learning. J Neurosci. 2009 Nov 11;29(45):14271-86.