SUCCINYLCHOLINE: STRUCTURE, ACTION AND WHAT IT IS FOR - CHEMISTRY - 2025

The succinylcholine or suxamethonium chloride is an organic compound, specifically a quaternary amine having pharmacological activity. It is a solid whose molecular formula is C ₁₄ H ₃₀ N ₂ O ₄ ⁺². Because it has a divalent positive charge, it forms organic salts with chloride, bromide, or iodide anions.

Succinylcholine is a drug that binds to nicotinic acetylcholine receptors on the postsynaptic membrane of the neuromuscular junction or end plate, causing its depolarization, blockage and flaccid muscle relaxation. This is due to the great structural similarity between it and acetylcholine.

Chemical structure

The top image illustrates the structure of succinylcholine. The positive charges are located on the two nitrogen atoms and, therefore, are surrounded by the Cl ^- ions through electrostatic interactions.

Its structure is very flexible, due to the many spatial possibilities that the rotations of all its simple links have. Likewise, it presents a plane of symmetry; its right side is the reflection of the left.

Structurally, succinylcholine can be considered as the union of two acetylcholine molecules. This can be verified by comparing each of its sides with said compound.

Mechanism of action (suxamethonium)

Acetylcholine causes a depolarization in the end plate that is able to move to neighboring muscle cells, allowing the entry of Na ⁺ and reaching the threshold membrane potential.

This leads to the production of action potentials in skeletal muscle cells that initiate their contraction.

The interaction of acetylcholine with its receptors is short-lived, because it is rapidly hydrolyzed by the enzyme acetylcholinesterase.

On the other hand, succinylcholine is less susceptible to the action of the indicated enzyme, which is why it remains bound to the nicotinic acetylcholine receptor for a longer time than this, causing a prolongation of depolarization.

This fact initially produces the asynchronous contraction of a group of skeletal muscle fibers, which is known as fasciculation. This is of short duration, being observed mainly in the thorax and in the abdomen.

Subsequently, the neuromuscular junction or end plate is blocked, with the consequent inactivation of Na ⁺ channels and, ultimately, the inability to contract skeletal muscle cells.

Nicotinic receptor

The nicotinic acetylcholine receptor of the postsynaptic membrane of the neuromuscular junction is made up of five subunits: 2α ₁, 1β ₁, 1δ, 1ε.

Succinylcholine only interacts with this receptor and does not bind to acetylcholine receptors on ganglion cells (α ₃, β ₄) and presynaptic nerve terminals (α ₃, β ₂).

Acetylcholine receptors at the postsynaptic terminal of the neuromuscular junction have a dual function, as they serve as Na ⁺ channels.

When acetylcholine binds to the α subunits, conformational changes occur that cause the opening of a channel that allows the entry of Na ⁺ and the exit of K ⁺.

Few of the actions of succinylcholine have been attributed to a possible interaction with the central nervous system, explained by its non-interaction with the acetylcholine receptors present in the central nervous system.

The cardiovascular effects of succinylcholine are not attributed to ganglionic blockage. These are probably due to the successive stimulation of the vagal ganglia, manifested by bradycardia, and stimulation of the sympathetic ganglia expressed with hypertension and tachycardia.

The flaccid paralysis of the skeletal muscle begins 30 to 60 seconds after succinylcholine is injected, reaching maximum activity after 1-2 minutes that lasts for 5 minutes.

What is it for?

- It acts as an adjunct to anesthetics in numerous surgical operations. Perhaps the most widespread use of succinylcholine is in endotracheal intubation, thus allowing adequate ventilation of the patient during a surgical procedure.

- Neuromuscular blocking agents act as aids to surgical anesthesia by causing relaxation of the skeletal muscle, particularly the abdominal wall, facilitating surgical intervention.

- Muscle relaxation is valuable in orthopedic procedures, the correction of dislocations and fractures. In addition, it has been used to facilitate laryngoscopy, bronchoscopy, and esophagoscopy in combination with a general anesthetic.

- It has been used to alleviate the manifestations of psychiatric patients subjected to electroconvulsions, as well as in the treatment of patients with persistent seizures associated with toxic drug reactions.

- Among the surgical interventions in which succinylcholine has been used, open heart surgery and intraocular surgery stand out, where the drug is administered 6 minutes before producing an eye incision.

Special cases

- Among the group of patients with a resistance to the action of succinylcholine are patients with hyperlipidemia, obesity, diabetes, psoriasis, bronchial asthma and alcoholism.

- Likewise, patients with myasthenia gravis, a condition in which the destruction of postsynaptic acetylcholine receptors is observed in the neuromuscular junctions, require higher doses of succinylcholine for its therapeutic action to be manifested.

Side effects

- Postoperative pain occurs regularly in the muscles of the neck, shoulders, sides and back.

- The use of succinylcholine should be avoided in patients with severe burns. This is due to the fact that the increase in K ⁺ output through the Na ⁺ and K ⁺ channels, which occurs during drug binding to acetylcholine receptors, increases the plasma concentration of K ⁺. As a consequence, it can lead to cardiac arrest.

- A drop in blood pressure, increased salivation, appearance of a skin rash, transient ocular hypertension and also constipation may be observed.

- As side effects, hypercalcemia, hyperthermia, apnea and increased histamine release also stand out.

- Likewise, the use of succinylcholine should be avoided in patients with congestive heart failure treated with digoxin or another digitalis glycoside.

References

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