Vesamicol Explained

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]

Notes and References

1. Salin-Pascual RJ, Jimenez-Anguiano A . Vesamicol, an acetylcholine uptake blocker in presynaptic vesicles, suppresses rapid eye movement (REM) sleep in the rat . Psychopharmacology . 121 . 4 . 485–7 . October 1995 . 8619013 . 10.1007/BF02246498 . 25197707 .
2. 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 . 6 . Inhibition of cholinergic signaling causes apoptosis in human bronchioalveolar carcinoma . Cancer Research . 73 . 4 . 1328–39 . February 2013 . 23222296 . 10.1158/0008-5472.CAN-12-3190 . 10461321 . free .
3. Book: Zucker RS, Kullmann DM, Kaesar PS . Release of Neurotransmitters . Byrne JH, Heidelberger R, Waxham MN . From Molecules to Networks - An Introduction to Cellular and Molecular Neuroscience\ . Academic Press. 2014. 978-0-12-397179-1. 3rd. 443–488. en. 10.1016/B978-0-12-397179-1.00015-4.