scholarly journals Expeditious Synthesis, Enantiomeric Resolution, and Enantiomer Functional Characterization of (4-(4-Bromophenyl)-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinoline-8-sulfonamide (4BP-TQS): An Allosteric Agonist-Positive Allosteric Modulator of α7 Nicotinic Acetylcholine Receptors

2013 ◽  
Vol 56 (21) ◽  
pp. 8943-8947 ◽  
Author(s):  
Ganesh A. Thakur ◽  
Abhijit R. Kulkarni ◽  
Jeffrey R. Deschamps ◽  
Roger L. Papke
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Functional Characterization ◽  
Allosteric Modulator ◽  
Positive Allosteric Modulator ◽  
Enantiomeric Resolution ◽  
Nicotinic Acetylcholine ◽  
Α7 Nicotinic Acetylcholine Receptors

3-Furan-2-yl-N-p-tolyl-acrylamide, a highly selective positive allosteric modulator of α7 nicotinic receptors, produces anxiolytic-like activity in mice

2019 ◽  
Vol 33 (5) ◽  
pp. 558-567 ◽  
Author(s):  
Katarzyna M Targowska-Duda ◽  
Barbara Budzynska ◽  
Agnieszka Michalak ◽  
Krzysztof Jozwiak ◽  
Grazyna Biala ◽  
...  
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Acute Treatment ◽  
Elevated Plus Maze ◽  
Allosteric Modulator ◽  
Positive Allosteric Modulator ◽  
Nicotinic Acetylcholine ◽  
Plus Maze ◽  
Α7 Nicotinic Acetylcholine Receptors ◽  
First Time

Background: Several lines of investigations support the idea that nicotinic acetylcholine receptors modulate neuronal pathways involved in anxiety and depression. Aims: The purpose of this study was to determine whether 3-furan-2-yl-N-p-tolyl-acrylamide, a highly selective positive allosteric modulator of α7 nicotinic acetylcholine receptors, influences anxiety-like behaviour in mice, and to determine the modulatory activity of 3-furan-2-yl-N-p-tolyl-acrylamide on mice pretreated with either nicotine or selective α7-agonists (i.e. PNU-282987 or (2.4)-dimethoxybenzylidene anabaseine dihydrochloride). Methods: The elevated plus maze and novelty suppressed feeding tests were selected to evaluate 3-furan-2-yl-N-p-tolyl-acrylamide and other nicotinic ligands on anxiety-like behaviour in mice. Results: The results indicated that: (a) 3-furan-2-yl-N-p-tolyl-acrylamide induces anxiolytic-like activity at 0.5 (elevated plus maze) and 1.0 (novelty suppressed feeding) mg/kg, respectively, after acute treatment, whereas its efficacy is increased after chronic treatments (i.e. active at 0.1 mg/kg; elevated plus maze). This is the first time showing anxiolytic-like activity elicited by 3-furan-2-yl-N-p-tolyl-acrylamide, contrary to the lack of activity for PNU-120596 (0.1 mg/kg); (b) the anxiolytic-like activity of 0.5 mg/kg 3-furan-2-yl-N-p-tolyl-acrylamide is inhibited by methyllycaconitine, a selective α7-antagonist, suggesting that α7 nicotinic acetylcholine receptors are involved in this process; (c) 0.5 mg/kg 3-furan-2-yl-N-p-tolyl-acrylamide reverses the anxiogenic effects induced by 0.1 mg/kg nicotine but not by 10.0 mg/kg PNU-282987; and (d) inactive doses of both 3-furan-2-yl-N-p-tolyl-acrylamide (0.1 mg/kg) and (2.4)-dimethoxybenzylidene anabaseine dihydrochloride (1.0 mg/kg) produce anxiolytic-like effects, suggesting drug interactions, probably synergistic. Conclusions: Our findings indicated that anxiolytic-like activity is mediated by α7 nicotinic acetylcholine receptors, supporting the concept that these receptors modulate anxiety processes. The results indicating that the chronic treatment with 3-furan-2-yl-N-p-tolyl-acrylamide is more efficient than the acute treatment in eliciting anxiolytic-like activity, and that 3-furan-2-yl-N-p-tolyl-acrylamide reverses the anxiogenic effects induced by nicotine, might be of therapeutic importance during smoking cessation.

Characterization of AN6001, a positive allosteric modulator of α6β2-containing nicotinic acetylcholine receptors

2020 ◽  
Vol 174 ◽  
pp. 113788 ◽  
Author(s):  
Marloes van Hout ◽  
Jessica Klein ◽  
Philip K. Ahring ◽  
David T. Brown ◽  
Siganya Thaneshwaran ◽  
...  
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Allosteric Modulator ◽  
Positive Allosteric Modulator ◽  
Nicotinic Acetylcholine

scholarly journals Galantamine is not a positive allosteric modulator of human α4β2 or α7 nicotinic acetylcholine receptors

2018 ◽  
Vol 175 (14) ◽  
pp. 2911-2925 ◽  
Author(s):  
Natalia M Kowal ◽  
Philip K Ahring ◽  
Vivian W Y Liao ◽  
Dinesh C Indurti ◽  
Benjamin S Harvey ◽  
...  
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Allosteric Modulator ◽  
Positive Allosteric Modulator ◽  
Nicotinic Acetylcholine ◽  
Α7 Nicotinic Acetylcholine Receptors

scholarly journals αM-Conotoxin MIIIJ Blocks Nicotinic Acetylcholine Receptors at Neuromuscular Junctions of Frog and Fish

Toxins ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 197
Author(s):  
Matthew J. Rybin ◽  
Henrik O’Brien ◽  
Iris Bea L. Ramiro ◽  
Layla Azam ◽  
J. Michael McIntosh ◽  
...  
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Neuromuscular Junctions ◽  
Functional Characterization ◽  
Cone Snail ◽  
Nicotinic Acetylcholine ◽  
New Class ◽  
Goldfish Carassius Auratus ◽  
Snake Neurotoxin

We report the discovery and functional characterization of αM-Conotoxin MIIIJ, a peptide from the venom of the fish-hunting cone snail Conus magus. Injections of αM-MIIIJ induced paralysis in goldfish (Carassius auratus) but not mice. Intracellular recording from skeletal muscles of fish (C. auratus) and frog (Xenopus laevis) revealed that αM-MIIIJ inhibited postsynaptic nicotinic acetylcholine receptors (nAChRs) with an IC50 of ~0.1 μM. With comparable potency, αM-MIIIJ reversibly blocked ACh-gated currents (IACh) of voltage-clamped X. laevis oocytes exogenously expressing nAChRs cloned from zebrafish (Danio rerio) muscle. αM-MIIIJ also protected against slowly-reversible block of IACh by α-bungarotoxin (α-BgTX, a snake neurotoxin) and α-conotoxin EI (α-EI, from Conus ermineus another fish hunter) that competitively block nAChRs at the ACh binding site. Furthermore, assessment by fluorescence microscopy showed that αM-MIIIJ inhibited the binding of fluorescently-tagged α-BgTX at neuromuscular junctions of X. laevis, C. auratus, and D. rerio. (Note, we observed that αM-MIIIJ can block adult mouse and human muscle nAChRs exogenously expressed in X. laevis oocytes, but with IC50s ~100-times higher than those of zebrafish nAChRs.) Taken together, these results indicate that αM-MIIIJ inhibits muscle nAChRs and furthermore apparently does so by interfering with the binding of ACh to its receptor. Comparative alignments with homologous sequences identified in other fish hunters revealed that αM-MIIIJ defines a new class of muscle nAChR inhibitors from cone snails.

Sign in / Sign up

Export Citation Format

Share Document