Directly Acting Muscle Relaxants: Dantrolene and Botulinum Toxin

Most skeletal muscle relaxants act on the central nervous system to relieve pain from muscle stiffness or weakness.

However, some muscle relaxants, such as dantrolene and botulinum toxin, act directly on the skeletal muscle cells.

Dantrolene binds the ryanodine receptor, RYR1, on the sarcoplasmic reticulum membrane of skeletal muscle cells and blocks the release of calcium ions. Lack of calcium reduces the tension-generating actin-myosin interaction, which relaxes the muscle tone and prevents unnecessary heat generation.

Due to such a cooling effect, dantrolene is also used to treat malignant hyperthermia, a life-threatening heritable condition triggered as a reaction to certain general anesthetics or neuromuscular blockers.

On the other hand, botulinum toxin is used to treat spastic disorders like cerebral palsy, and multiple sclerosis.

At the neuromuscular junction, the active toxin acts on vesicle fusion proteins such as SNAP-25 or synaptobrevin-2 and induces their proteolytic cleavage.

This interferes with vesicle fusion and inhibits the exocytosis of acetylcholine from the presynaptic nerve terminal, partially paralyzing muscle fibers.