Inhibitors of acetylcholine release
Botulinum toxin, produced by the bacillus gram positive, anaerobic and sporulant, Clostridium botulinum, binds to cholinergic terminations, in particular neuromuscular, in which it penetrates by endocytosis. Botulinum toxin is a zinc enzyme which, inside the cytoplasm, hydrolyzes proteins like synaptobrevin, VAMP (vesicle-associated membrane protein) necessary for the migration and exocytosis of the vesicles containing acetylcholine. It inhibits the acetylcholine release.
Botulism, which is more like a poisoning than an infection, results in a paresis or a paralysis of the muscles ensuring ocular motricity, swallowing, elocution, posture and locomotion. A dryness of the mouth is also observed.
Botulinum toxin is currently the only inhibitor of the release of acetylcholine used in therapeutics. Administered locally in a muscle, it penetrates inside presynaptic cholinergic terminations and inhibits acetylcholine release. It elicits a true denervation of the muscles which are atrophied.
It is used in the treatment of dystonia, blepharospasm, spasmodic torticollis, facial hemispasm, strabismus. Injected into the lower sphincter of the esophagus, it improves a disorder of the motility of the esophagus, called achalasy. Its effect appears in two or three days and lasts a long time, approximately three months. It is in addition used in the treatment of wrinkles.
The principal danger of botulinum toxin injected locally is its diffusion to other muscles close to those which one wishes to inhibit and which are inopportunely paralyzed.
Remarks
- Piperazine
Piperazine is an antihelminthic active in the treatment of oxyuriasis (Enterobius vermicularis) and ascaridiasis (Ascaris lumbricoides). Piperazine causes a flaccid paralysis of sensitive worms attributed to inhibition of nicotinic effects of acetylcholine. Worms are expelled in faeces. Although absorbed by the digestive tract, piperazine in human beings elicits no neuromuscular inhibition. The reason of its selectivity of action on worms is not known.
- Pyrantel
Pyrantel is an antihelminthic active against Enterobius vermicularis, Ascaris lumbricoides, Ankylostoma duodenal, Necator americanus, Trichuris trichiura. Pyrantel causes a persistent activation of nicotinic acetylcholine receptors which induces depolarization and contracture of sensible worms; moreover it inhibits cholinesterases. Paralysis is at the origin of the expulsion of the worms.It is little absorbed by the digestive tract.. When it is given in by parenteral route in animal experiments, it induces paralysis due to the inhibition of the neuromuscular transmission.
Pyrantel has a mechanism of action opposed to that of piperazine. These two products being antagonist should not be used simultaneously.
- There is another drug used in the treatment of oxyurose, pyrvinium acting by a mechanism poorly understood but different from that of pyrantel.
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