The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
Chemical Compound Review

CHEMBL277861     (1S,2S)-2-(4-phenyl-1- piperidyl)cyclohexan...

Synonyms: SureCN4499984, CHEBI:125268, LS-57232, AC1LH8IN, (+)-Vesamicol, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of (+)-Vesamicol


Psychiatry related information on (+)-Vesamicol


High impact information on (+)-Vesamicol


Biological context of (+)-Vesamicol

  • It is concluded that many drugs can bind to the vesamicol receptor and binding to only a small fraction of the receptors can result in AcCh active transport inhibition [10].
  • Use of trace [3H]vesamicol and [14C]AcCh allowed simultaneous determination of the concentrations of enantiomer, analogue, or drug required to half-saturate the vesamicol receptor (Ki) and to half-inhibit transport (IC50), respectively [10].
  • We suggest that PKC alters the output of [3H]ACh formed in the presence of vesamicol and also provide circumstantial evidence for a role of phosphorylation of VAChT in this process [11].
  • These results suggest that ouabain releases a vesamicol-insensitive pool of ACh from the sympathetic ganglion and also support the notion that this compartment is vesicular and its exocytosis depends on extracellular Ca2+ [12].
  • The data demonstrate that the vesamicol family of compounds binds to an allosteric site in the AcChT [13].

Anatomical context of (+)-Vesamicol

  • The lead-induced release of [3H]ACh was blocked by treatment of synaptosomes with vesamicol, which prevents uptake of ACh into synaptic vesicles without affecting its synthesis in the synaptoplasm [14].
  • Initial studies presented in this article demonstrate the existence of a specific, saturable vesamicol binding site in PC12 cells [15].
  • Moreover, this effect of vesamicol was (a) concentration-dependent and saturable (EC50 = 68 nM), (b) rapidly reversible, (c) stereospecific for the L-isomer, and (d) poorly mimicked by a vesamicol analog with lower plasma membrane permeability [16].
  • In the presence of Ca2+, coincident with the release of the vesamicol-insensitive pool of ACh, nerve terminals were almost depleted of synaptic vesicles; ganglia treated similarly, but with medium containing 18 mM Mg2+ instead of Ca2+, were not depleted of synaptic vesicles [12].
  • The properties of the receptor for vesamicol were studied by measuring binding of [3H]vesamicol, and the amount of SV2 antigen characteristic of secretory vesicles was assayed with a monoclonal antibody directed against it [17].

Associations of (+)-Vesamicol with other chemical compounds


Gene context of (+)-Vesamicol

  • Levels of the VAChT were reduced by a range of 13-31% on PND 3 through 30 in the high-dosage group, using 3H-AH5183 (vesamicol) as the ligand [23].
  • Treatment of slices with the PKC activator phorbol myristate acetate (PMA) decreased the inhibitory effect of vesamicol on [3H]ACh release [11].
  • Recovery was blocked by (-)-vesamicol (VES), by hemicholinium-3 (HC3) and by nicotinic cholinergic agonists - all of which inhibit ACh loading into synaptic vesicles [24].
  • At 23 degrees C, [3H]vesamicol bound to the receptor at a rate of (1.74 +/- 0.06) x 10(5) M-1 s-1, and excess unlabeled vesamicol displaced a low concentration of bound [3H]vesamicol at 0.29 +/- 0.01 min-1 [25].
  • In particular, vesamicol binding compartments have a lower density than catecholaminergic vesicles and, unlike these latter vesicles, do not appear to contain the vesicle-specific proteins synaptophysin and SV2 as part of the same membrane [15].

Analytical, diagnostic and therapeutic context of (+)-Vesamicol

  • The observed difference between the equilibrium dissociation constant for the vesamicol-VR complex as estimated by titration with [3H]vesamicol (7.6 nM) and by displacement of subsaturating [3H]vesamicol by nonlabeled vesamicol (1.0 nM) suggests that high and low affinity populations of the VR exist [9].
  • A similar inhibitory effect was produced by direct intrastriatal perfusion with vesamicol [16].
  • Vesamicol inhibited [14C]ACh release evoked by both veratridine and electrical stimulation in the presence of external Ca2+, provided it was added to the tissue prior to loading with [14C]choline [26].
  • 4. Further studies with the active isomer, (-)-vesamicol, showed that, like that produced by racemic vesamicol, the neuromuscular block was highly frequency-dependent [27].
  • Direct optical resolution of vesamicol and a series of benzovesamicol analogues by high-performance liquid chromatography [28].


  1. Functional identification of a vesicular acetylcholine transporter and its expression from a "cholinergic" gene locus. Erickson, J.D., Varoqui, H., Schäfer, M.K., Modi, W., Diebler, M.F., Weihe, E., Rand, J., Eiden, L.E., Bonner, T.I., Usdin, T.B. J. Biol. Chem. (1994) [Pubmed]
  2. Transmitter-mediated local contracture of the endplate region of the focally innervated mouse diaphragm treated with anticholinesterase. Hong, S.J., Chang, C.C. Br. J. Pharmacol. (1993) [Pubmed]
  3. Synthesis and evaluation of radiolabeled piperazine derivatives of vesamicol as SPECT agents for cholinergic neurons. Bando, K., Taguchi, K., Ginoza, Y., Naganuma, T., Tanaka, Y., Koike, K., Takatoku, K. Nucl. Med. Biol. (2001) [Pubmed]
  4. Vesamicol, an acetylcholine uptake blocker in presynaptic vesicles, suppresses rapid eye movement (REM) sleep in the rat. Salin-Pascual, R.J., Jimenez-Anguiano, A. Psychopharmacology (Berl.) (1995) [Pubmed]
  5. Choline acetyltransferase activity and vesamicol binding in Rett syndrome and in rats with nucleus basalis lesions. Wenk, G.L., Mobley, S.L. Neuroscience (1996) [Pubmed]
  6. Reduction of vesicular acetylcholine transporter in beta-amyloid protein-infused rats with memory impairment. Ikeda, E., Shiba, K., Mori, H., Ichikawa, A., Sumiya, H., Kuji, I., Tonami, N. Nuclear medicine communications. (2000) [Pubmed]
  7. Phosphorylation of the rat vesicular acetylcholine transporter. Cho, G.W., Kim, M.H., Chai, Y.G., Gilmor, M.L., Levey, A.I., Hersh, L.B. J. Biol. Chem. (2000) [Pubmed]
  8. Mutational analysis of aspartate residues in the transmembrane regions and cytoplasmic loops of rat vesicular acetylcholine transporter. Kim, M.H., Lu, M., Lim, E.J., Chai, Y.G., Hersh, L.B. J. Biol. Chem. (1999) [Pubmed]
  9. Kinetic and equilibrium characterization of vesamicol receptor-ligand complexes with picomolar dissociation constants. Rogers, G.A., Kornreich, W.D., Hand, K., Parsons, S.M. Mol. Pharmacol. (1993) [Pubmed]
  10. Fractional vesamicol receptor occupancy and acetylcholine active transport inhibition in synaptic vesicles. Kaufman, R., Rogers, G.A., Fehlmann, C., Parsons, S.M. Mol. Pharmacol. (1989) [Pubmed]
  11. Effect of protein kinase C activation on the release of [3H]acetylcholine in the presence of vesamicol. Barbosa, J., Clarizia, A.D., Gomez, M.V., Romano-Silva, M.A., Prado, V.F., Prado, M.A. J. Neurochem. (1997) [Pubmed]
  12. Mobilization of a vesamicol-insensitive pool of acetylcholine from a sympathetic ganglion by ouabain. Prado, M.A., Gomez, M.V., Collier, B. J. Neurochem. (1993) [Pubmed]
  13. A kinetic and allosteric model for the acetylcholine transporter-vesamicol receptor in synaptic vesicles. Bahr, B.A., Clarkson, E.D., Rogers, G.A., Noremberg, K., Parsons, S.M. Biochemistry (1992) [Pubmed]
  14. Ca2(+)-surrogate action of Pb2+ on acetylcholine release from rat brain synaptosomes. Shao, Z., Suszkiw, J.B. J. Neurochem. (1991) [Pubmed]
  15. Vesamicol binding to subcellular membranes that are distinct from catecholaminergic vesicles in PC12 cells. Blumberg, D., Schweitzer, E.S. J. Neurochem. (1992) [Pubmed]
  16. Suppression of in vivo neostriatal acetylcholine release by vesamicol: evidence for a functional role of vesamicol receptors in brain. Marien, M.R., Richard, J.W., Allaire, C., Altar, C.A. J. Neurochem. (1991) [Pubmed]
  17. Cholinergic synaptic vesicle heterogeneity: evidence for regulation of acetylcholine transport. Gracz, L.M., Wang, W.C., Parsons, S.M. Biochemistry (1988) [Pubmed]
  18. Purification and characterization of a nonvesicular vesamicol-binding protein from electric organ and demonstration of a related protein in mammalian brain. Hicks, B.W., Rogers, G.A., Parsons, S.M. J. Neurochem. (1991) [Pubmed]
  19. Acetylcholine synthesis by a sympathetic ganglion in the presence of 2-(4-phenylpiperidino)cyclohexanol (AH5183) and picrylsulfonic acid. Mykita, S., Collier, B. J. Neurochem. (1989) [Pubmed]
  20. Recycling and refilling of transmitter quanta at the frog neuromuscular junction. Van der Kloot, W., Colasante, C., Cameron, R., Molgó, J. J. Physiol. (Lond.) (2000) [Pubmed]
  21. Increasing quantal size at the mouse neuromuscular junction and the role of choline. Yu, S.P., Van der Kloot, W. J. Physiol. (Lond.) (1991) [Pubmed]
  22. Effect of N,N'-dicyclohexylcarbodiimide on the binding of vesamicol, an inhibitor of acetylcholine transport into synaptic vesicles. Diebler, M.F. Neurochem. Int. (1992) [Pubmed]
  23. Neurochemical effects of repeated gestational exposure to chlorpyrifos in developing rats. Richardson, J.R., Chambers, J.E. Toxicol. Sci. (2004) [Pubmed]
  24. Repetitive nerve stimulation decreases the acetylcholine content of quanta at the frog neuromuscular junction. Naves, L.A., Van der Kloot, W. J. Physiol. (Lond.) (2001) [Pubmed]
  25. Sidedness and chemical and kinetic properties of the vesamicol receptor of cholinergic synaptic vesicles. Kornreich, W.D., Parsons, S.M. Biochemistry (1988) [Pubmed]
  26. Ca2+o-independent veratridine-evoked acetylcholine release from striatal slices is not inhibited by vesamicol (AH5183): mobilization of distinct transmitter pools. Adam-Vizi, V., Deri, Z., Vizi, E.S., Sershen, H., Lajtha, A. J. Neurochem. (1991) [Pubmed]
  27. A further study of the neuromuscular effects of vesamicol (AH5183) and of its enantiomer specificity. Estrella, D., Green, K.L., Prior, C., Dempster, J., Halliwell, R.F., Jacobs, R.S., Parsons, S.M., Parsons, R.L., Marshall, I.G. Br. J. Pharmacol. (1988) [Pubmed]
  28. Direct optical resolution of vesamicol and a series of benzovesamicol analogues by high-performance liquid chromatography. Gildersleeve, D.L., Jung, Y.W., Wieland, D.M. Journal of chromatography. A. (1994) [Pubmed]
WikiGenes - Universities