PubMed: 28132910

Title
B-973, a novel piperazine positive allosteric modulator of the α7 nicotinic acetylcholine receptor.
Journal
European journal of pharmacology
Volume
799
Issue
None
Pages
16-25
Date
2017-03-15
Authors
Post-Munson DJ | Herrington J | Ahlijanian MK | Bristow LJ | Graef JD | Hendricson AW | Kiss L | Knox RJ | Macor JE | McDonald IM | Molski TF | Olson RE | Pieschl RL | Weed MR

Evidence 086a430f73

PNU-120596 and B-973 enhanced [3H]A-585539 binding to rat brain membranes (Fig. 5B,C)

Evidence a55ca675b0

[3H]A-585539 saturation binding revealed that B-973 and PNU-120596 increased the affinity of the receptor for [3H]A-585539 approximately 4-fold without changing the apparent Bmax (Fig. 5D)

Evidence d49df4f7d7

As expected, binding was inhibited by epibatidine (Fig. 5A)

Evidence b38fdb37e6

Peak current was increased 2-fold and 6-fold relative to 3 mM acetylcholine in 300 nM and 1 μM B-973, respectively (Fig. 1C)

Evidence 8f1a374425

B-973 slows receptor deactivation dramatically (Fig. 4A)

Evidence fdd7ae4f71

The amplitude of currents were dose dependent, reaching levels at 30 μM B-973 larger than control currents in response to 3 mM acetylcholine (Fig. 7A)

Evidence 875d6ce1bc

The currents induced by B-973 alone arise from the α7 receptor since methyllycaconitine blocks them nearly completely (Fig. 7C and Fig. S6)

Evidence 2556c5c570

Over the concentration range studied, B-973 increased the potency of acetylcholine at the α7 receptor 70-fold (control acetylcholine EC50=0.49 mM; acetylcholine EC50 at 1 μM B-973=0.007 mM)

Evidence 4abd963f31

At the highest PAM concentration tested (10 μM), the percent increase in [3H]A-585539 binding was much greater for recombinant α7 than that observed with rat brain membranes

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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.