Vesamicol
{{Short description|Chemical compound}}
{{Drugbox
| IUPAC_name = 2-(4-Phenyl-1-piperidyl)cyclohexan-1-ol
| image = Vesamicol.png
| tradename =
| pregnancy_category =
| legal_status = Investigational
| routes_of_administration =
| bioavailability =
| protein_bound =
| metabolism =
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| CAS_number_Ref = {{cascite|correct|CAS}}
| CAS_number = 22232-64-0
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 3D416V0FLM
| IUPHAR_ligand = 4759
| ATC_prefix =
| ATC_suffix =
| PubChem = 5662
| ChemSpiderID = 5460
| ChEMBL = 20730
| C = 17 | H = 25 | N = 1 | O = 1
| smiles = OC1CCCCC1N2CCC(CC2)c3ccccc3
}}
Vesamicol is an experimental drug, acting presynaptically by inhibiting acetylcholine (ACh) uptake into synaptic vesicles and reducing its release.{{cite journal | vauthors = Salin-Pascual RJ, Jimenez-Anguiano A | title = Vesamicol, an acetylcholine uptake blocker in presynaptic vesicles, suppresses rapid eye movement (REM) sleep in the rat | journal = Psychopharmacology | volume = 121 | issue = 4 | pages = 485–7 | date = October 1995 | pmid = 8619013 | doi = 10.1007/BF02246498 | s2cid = 25197707 }} Vesamicol may have applications for the treatment of adenocarcinoma in situ of the lung.{{cite journal | vauthors = Lau JK, Brown KC, Thornhill BA, Crabtree CM, Dom AM, Witte TR, Hardman WE, McNees CA, Stover CA, Carpenter AB, Luo H, Chen YC, Shiflett BS, Dasgupta P | display-authors = 6 | title = Inhibition of cholinergic signaling causes apoptosis in human bronchioalveolar carcinoma | journal = Cancer Research | volume = 73 | issue = 4 | pages = 1328–39 | date = February 2013 | pmid = 23222296 | doi = 10.1158/0008-5472.CAN-12-3190 | pmc = 10461321 | url = http://cancerres.aacrjournals.org/content/early/2012/12/06/0008-5472.CAN-12-3190.full.pdf | doi-access = free }}
Mechanism of action
Vesamicol can be broadly categorized as a cholinergic physiological antagonist, because it reduces the apparent activity of cholinergic neurons, but does not act at the postsynaptic ACh receptor. Vesamicol causes a non-competitive and reversible block of the intracellular transporter VAChT responsible for carrying newly synthesized ACh into secretory vesicles in the presynaptic nerve terminal. This transport process is driven by a proton gradient between cell organelles and the cytoplasm. Blocking of acetylcholine loading leads to empty vesicles fusing with neuron membranes, decreasing ACh release.{{Cite book| vauthors = Zucker RS, Kullmann DM, Kaesar PS |chapter=Release of Neurotransmitters | veditors = Byrne JH, Heidelberger R, Waxham MN |title=From Molecules to Networks - An Introduction to Cellular and Molecular Neuroscience\ |publisher=Academic Press|year=2014|isbn=978-0-12-397179-1|edition=3rd|pages=443–488|language=en|doi=10.1016/B978-0-12-397179-1.00015-4}}
References
{{Reflist}}
{{Acetylcholine metabolism and transport modulators}}
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