BQCA
CAS No. : 338747-41-4

BQCA
Cat. No. : CS-6880
M. Wt. : 309.32
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10mg In-stock $96.0
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  • Data Sheet

  • Introduction

  • SDS

  • COA & Spectra

Name: BQCA; 
Cat. No. : CS-6880
CAS No. : 338747-41-4
Formula: C18H15NO4
M. Wt. : 309.32

Activity:

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].

Protocol:

Kinase Assay: [1]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]. Animal Administration: [1][2]Rat: Male Sprague-Dawley rats weighing 225–250 g, are injected i.p. with the micro-suspension (containing 10% tween 80) of BQCA at the dose of 10 mg/kg. The blood and whole brain tissue samples are collected at 0.5, 1, 2, 4 and 8 h. Blood samples are collected through cardiac puncture in EDTA vacutainer tubes. The plasma is separated by centrifugation and stored at −80°C until analysis. The animals are decapitated and the whole brain tissue are removed and immediately frozen on dry ice[2].

Mouse: Mice are dosed I.P. with BQCA in 5% beta-cyclodextrin and/or 0.3 mg/kg scopolamine in 0.9% saline 30 min before placement into a chamber for 2 min before 2 tone-footshock pairings (3 kHz, 85 dB tone for 30 s co-terminated with a 0.5 mA, 1 s shock) 2 min apart. Mice are removed to their home cage 30 s after the last pairing. Twenty-four hours later mice are placed into the same chamber and freezing is measured by Video Freeze[1].

References:

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.

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.

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