Vesamicol

Vesamicol

Legal status
Legal status	Investigational
Identifiers
IUPAC name 2-(4-Phenyl-1-piperidyl)cyclohexan-1-ol
CAS Number	22232-64-0  Y
PubChem CID	5662
IUPHAR/BPS	4759
ChemSpider	5460
UNII	3D416V0FLM
ChEMBL	ChEMBL20730
CompTox Dashboard (EPA)	DTXSID701009898
Chemical and physical data
Formula	C17H25NO
Molar mass	259.393 g·mol−1
3D model (JSmol)	Interactive image
SMILES OC1CCCCC1N2CCC(CC2)c3ccccc3

Vesamicol is an experimental drug, acting presynaptically by inhibiting acetylcholine (ACh) uptake into synaptic vesicles and reducing its release. ^[1] Vesamicol may have applications for the treatment of adenocarcinoma in situ of the lung. ^[2]

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. ^[3]

References

1. Salin-Pascual RJ, Jimenez-Anguiano A (October 1995). "Vesamicol, an acetylcholine uptake blocker in presynaptic vesicles, suppresses rapid eye movement (REM) sleep in the rat". Psychopharmacology. 121 (4): 485–7. doi:10.1007/BF02246498. PMID   8619013. S2CID   25197707.
2. Lau JK, Brown KC, Thornhill BA, Crabtree CM, Dom AM, Witte TR, et al. (February 2013). "Inhibition of cholinergic signaling causes apoptosis in human bronchioalveolar carcinoma" (PDF). Cancer Research. 73 (4): 1328–39. doi: 10.1158/0008-5472.CAN-12-3190 . PMC   10461321 . PMID   23222296.
3. Zucker RS, Kullmann DM, Kaesar PS (2014). "Release of Neurotransmitters". In Byrne JH, Heidelberger R, Waxham MN (eds.). From Molecules to Networks - An Introduction to Cellular and Molecular Neuroscience\ (3rd ed.). Academic Press. pp. 443–488. doi:10.1016/B978-0-12-397179-1.00015-4. ISBN   978-0-12-397179-1.