ArticleMolecular pharmacology2009
Selective inhibition of acetylcholine-evoked responses of alpha7 neuronal nicotinic acetylcholine receptors by novel tris- and tetrakis-azaaromatic quaternary ammonium antagonists.
Article in Molecular pharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- Therapeutic Targeting ofPharmacological reviews · 2021Review
- Characterizing the Access of Cholinergic Antagonists to Efferent Synapses in the Inner Ear.Frontiers in neuroscience · 2021Article
- Larvicidal, Histopathological, Antibacterial Activity of Indigenous FungusFrontiers in microbiology · 2019Article
- Persistent activation of α7 nicotinic ACh receptors associated with stable induction of different desensitized states.British journal of pharmacology · 2018Article
- Two novel α7 nicotinic acetylcholine receptor ligands: in vitro properties and their efficacy in collagen-induced arthritis in mice.PloS one · 2015Article
- Merging old and new perspectives on nicotinic acetylcholine receptors.Biochemical pharmacology · 2014Review
- Multiple modes of α7 nAChR noncompetitive antagonism of control agonist-evoked and allosterically enhanced currents.Molecular pharmacology · 2013Article
- Defining the putative inhibitory site for a selective negative allosteric modulator of human α4β2 neuronal nicotinic receptors.ACS chemical neuroscience · 2012Article
- Structure-activity relationship studies of sulfonylpiperazine analogues as novel negative allosteric modulators of human neuronal nicotinic receptors.Journal of medicinal chemistry · 2011Article
- The novel small molecule α9α10 nicotinic acetylcholine receptor antagonist ZZ-204G is analgesic.European journal of pharmacology · 2011Article
- Positive allosteric modulators as an approach to nicotinic acetylcholine receptor-targeted therapeutics: advantages and limitations.Biochemical pharmacology · 2011Review
- Discovery of non-peptide, small molecule antagonists of α9α10 nicotinic acetylcholine receptors as novel analgesics for the treatment of neuropathic and tonic inflammatory pain.Bioorganic & medicinal chemistry letters · 2011Article
- Discovery of novel alpha7 nicotinic receptor antagonists.Bioorganic & medicinal chemistry letters · 2010Article
- Enhancement of attentional performance by selective stimulation of alpha4beta2(*) nAChRs: underlying cholinergic mechanisms.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2010Article
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7 authors at 2 institutions in 1 country.
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Abstract
A family of 20 tris-azaaromatic quaternary ammonium (AQA) compounds were tested for their inhibition of alpha7 nicotinic acetylcholine receptors (nAChRs) expressed in Xenopus laevis oocytes. The potency of inhibitory activity was related to the hydrophobic character of the tris head groups. Two tris-AQA compounds were studied in detail: the highly effective inhibitor 1,3,5-tri-[5-(1-quinolinum)-pent-1-yn-1-yl]-benzene tribromide (tPyQB) and the less potent antagonist 1,3,5,-tri-{5-[1-(2-picolinium)]-pent-1-yn-1-yl}benzene tribromide (tPy2PiB). In addition, we evaluated 1,2,4,5-tetra-{5-[1-(3-benzyl)pyridinium]pent-1-yl}benzene tetrabromide (tkP3BzPB), a tetrakis-AQA with very hydrophobic headgroups. We compared the activity of the AQA compounds to the frequently used alpha7-antagonist methyllycaconitine (MLA). Both tPyQB and tkP3BzPB were selective antagonists of alpha7. However, although inhibition by tPyQB was reversible within 5 min, the recovery time constant for tkP3BzPB inhibition was 26.6 +/- 0.8 min, so that the equilibrium inhibition in the prolonged presence of nanomolar concentrations of tkP3BzPB was nearly 100%. The potency, selectivity, and slow reversibility of tkP3BzPB were comparable with or greater than that of MLA. The inhibitory actions of tPyQB, tPy2PiB, and tkP3BzPB were evaluated on the acetylcholine (ACh)-evoked responses of native nAChRs in rat brain slices. The alpha7-mediated responses of hippocampal interneurons were effectively reduced by 1 microM tPyQB and tkP3BzPB but not tPy2PiB. In rat medial septum, tkP3BzPB produced a greater inhibition of ACh-evoked responses of cells with fast inward currents (type I) than of cells with predominantly slow kinetics (type II), suggesting that tkP3BzPB can block alpha7 yet preserve the responsiveness of non-alpha7 receptors. These agents might be helpful in elucidating complex receptor responses in brain regions with mixed populations of nAChRs.
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