Muscle relaxants, peripheral

Muscle relaxants are drugs that cause temporary paralysis or relaxation of the skeletal muscles.

Peripheral muscle relaxants exert their effect on the intracellular Ca2+ stores of the skeletal muscles. They are mainly used for muscle relaxation under anaesthesia. A distinction is made between 2 groups:

• Neuromuscular blocking substances acting as agonists and antagonists of NM-receptors (muscular type of nicotine receptors that activate an ion channel with high conductivity for Na+ and K+ ions). They can be further subdivided:
  • Non-depolarising muscle relaxants (NM receptor antagonists). As competitive inhibitors, they compete with acetylcholine for the receptor binding site. Their binding does not lead to the excitation of the NM-receptor and thus not to depolarization of the motor endplate.
  • Depolarizing muscle relaxants (agonists of the NM-receptor on the motor end plate). Their interaction with the receptor triggers a long-lasting depolarisation of the motor endplate, which makes excitation by acetylcholine impossible in this phase. This state of unexcitability is called depolarisation or phase-I block of neuromuscular transmission. The result is a flaccid muscle paralysis that cannot be reversed by cholinesterase inhibitors. Long-lasting phase I block (repetitive application of suxamethonium) can be followed by a phase II block which can be partially reversed by cholinesterase inhibitors. The classic representative of this substance group is suxamethonium (succinylcholine), a pharmaceutical in which two acetylcholine molecules are linked to their acyl residues.
• Muscular blocking substances which block the electronic coupling by inhibiting the release of Ca2+ within the skeletal muscle cell and are called myotropic muscle relaxants. The only relevant representative is dantrolene. Dantrolene binds to the RyR1 protein and suppresses the ability of Ca2+and calmodulin to activate the ryanodine receptor channel.