Can acetylcholine leak away from the synapse and cause spasms? I am currently studying Pharmacology and a question came to mind. We know that Acetylcholine is used as a neurotransmitter in the neuromuscular junction, both Sympathetic as Parasympathetic, but as I understand, correct me if I am wrong, they don't interfere with each other because of their locations being physically separated. My question is, could somehow occur the incomplete absorption of Acetylcholine in the receptor of the organ, let's say for a Parasympathetic response and it "leaked" to a nearby muscle or even into a Sympathetic receptor and create a involuntary movement for example?

The enzyme responsible for the breakdown of acetylcholine (Ach), _i.e._ , acetylcholinesterase, rapidly degrades, and inactivates Ach in the synaptic cleft after release. This process is particularly fast, as the synapse has to be cleared of neurotransmitter for a next action potential to occur (Čolović _et al_., 2013). So no, Ach does not leak away under physiologiocal conditions (Fig. 1).

In fact, common **cholinesterase inhibitors** that lead to Ach buildup by inhibiting its degradation, do not cause involuntary muscle twitches (spasms) as side effect. However, they do evoke muscle cramps, but that is easily explained by the increased retention of Ach in the synaptic cleft, leading to prolonged muscle contraction.

![cholinesterase](
Fig. 1. Cholinesterase is active in the synaptic cleft. source: Health & Fitness.

**Reference**
**-** Čolović _et al_., _Curr Neuropharmacol_ (2013); **11** (3): 315–35