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

a(CHEBI:"1-(5-chloro-2,4-dimethoxyphenyl)-3-(5-methyl-3-isoxazolyl)urea") increases complex(a(GO:membrane), a(PUBCHEM:16068384)) View Subject | View Object

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Annotations
MeSH
Brain

a(HBP:"B-973") increases complex(a(GO:membrane), a(PUBCHEM:16068384)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

Evidence a55ca675b0
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[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)

a(CHEBI:"1-(5-chloro-2,4-dimethoxyphenyl)-3-(5-methyl-3-isoxazolyl)urea") increases complex(a(MESH:"alpha7 Nicotinic Acetylcholine Receptor"), a(PUBCHEM:16068384)) View Subject | View Object

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a(HBP:"B-973") increases complex(a(MESH:"alpha7 Nicotinic Acetylcholine Receptor"), a(PUBCHEM:16068384)) View Subject | View Object

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Evidence d49df4f7d7
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As expected, binding was inhibited by epibatidine (Fig. 5A)

a(CHEBI:epibatidine) decreases complex(a(MESH:"alpha7 Nicotinic Acetylcholine Receptor"), a(PUBCHEM:16068384)) View Subject | View Object

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Evidence b38fdb37e6
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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)

a(HBP:"B-973") increases act(a(MESH:"alpha7 Nicotinic Acetylcholine Receptor")) View Subject | View Object

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Evidence 8f1a374425
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B-973 slows receptor deactivation dramatically (Fig. 4A)

a(HBP:"B-973") negativeCorrelation act(a(MESH:"alpha7 Nicotinic Acetylcholine Receptor")) View Subject | View Object

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act(a(MESH:"alpha7 Nicotinic Acetylcholine Receptor")) negativeCorrelation a(HBP:"B-973") View Subject | View Object

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Evidence fdd7ae4f71
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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)

a(HBP:"B-973") increases act(a(MESH:"alpha7 Nicotinic Acetylcholine Receptor")) View Subject | View Object

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Evidence 875d6ce1bc
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The currents induced by B-973 alone arise from the α7 receptor since methyllycaconitine blocks them nearly completely (Fig. 7C and Fig. S6)

a(HBP:"B-973") increases act(a(MESH:"alpha7 Nicotinic Acetylcholine Receptor")) View Subject | View Object

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a(PUBCHEM:5288811) decreases act(a(MESH:"alpha7 Nicotinic Acetylcholine Receptor")) View Subject | View Object

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Evidence 2556c5c570
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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)

a(HBP:"B-973") increases act(a(CHEBI:acetylcholine)) View Subject | View Object

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Evidence 4abd963f31
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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

a(HBP:"B-973") increases complex(a(PUBCHEM:16068384), p(MGI:Chrna7)) View Subject | View Object

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