Vesamicol is an experimental drug, acting

presynaptic In the nervous system, a synapse is a structure that allows a neuron (or nerve cell) to pass an electrical or chemical signal to another neuron or a target effector cell. Synapses can be classified as either chemical or electrical, depending o ...

ally by inhibiting

acetylcholine Acetylcholine (ACh) is an organic compound that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Par ...

(ACh) uptake into synaptic vesicles and reducing its release. Vesamicol may have applications for the treatment of

adenocarcinoma in situ of the lung Adenocarcinoma in situ (AIS) of the lung —previously included in the category of "bronchioloalveolar carcinoma" (BAC)—is a subtype of lung adenocarcinoma. It tends to arise in the distal bronchioles or alveoli and is defined by a non-invasive ...

Mechanism of action

Vesamicol can be broadly categorized as a cholinergic

physiological antagonist Physiological agonism describes the action of a substance which ultimately produces the same effects in the body as another substance—as if they were both agonists at the same receptor—without actually binding to the same receptor. Physiological ...

, because it reduces the apparent activity of cholinergic

neuron A neuron (American English), neurone (British English), or nerve cell, is an membrane potential#Cell excitability, excitable cell (biology), cell that fires electric signals called action potentials across a neural network (biology), neural net ...

s, 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.

References

4-Phenylpiperidines Cyclohexanols Phenyl compounds {{antineoplastic-drug-stub