Muscle relaxants, non-depolarising

Group of so-called "curare-like muscle relaxants" which, as antagonists of the NM nicotine receptor of the NM type on the motor end plate, block the effect of acetylcholine. The prototype substance of curare (South American arrow poison) is tubocurarin.

Tubocurarin

Atracurium

Mivacurium

Pancuronium

Vecuronium

All substances contain at least one quaternary nitrogen group, are therefore polar and therefore cannot pass the blood-brain barrier. They are not centrally effective.

Kinetics: After i.v. administration the substances are excreted renally and biliarily. Some are cleaved by unspecific esterases.

NW: Histamine release is observed to a pronounced degree when Tubocurarin is administered, but only to a small extent for the substances Alcuronium, Atracurium, Pancuronium.

The curare-type muscle relaxants as NM receptor antagonists are not absorbed as compounds with quaternary nitrogen (ammonium compounds) after peroral administration. They must therefore be administered i.v. (Note: animals killed with curare could be eaten without danger).

They cause competitive antagonism of the NM receptor of the motor end plate. This causes a reduction in the amplitude of the endplate potential so that the critical threshold for activation of the voltage-dependent "fast Na+ channels" of the muscle fiber is not reached. The result is muscle paralysis. The effect can be broken by increasing the acetylcholine concentration. Indirect-acting parasympathomimetics = cholinesterase inhibitors such as neostigmine are used, although they also require the administration of a vagolytic, as they do not specifically act on the motor end plate.

A chelating agent such as sugammadex, a modified gamma-cyclodextrin binds curare-type muscle relaxants in plasma, terminating their efficacy. Sugammadex has a high specificity and thus acquires an increasing importance.

Important: The paralysis also affects the respiratory muscles(but not the cardiac muscles) so that the patient must be intubated.

Non-depolarising muscle relaxants are used for muscle relaxation during major surgery, to facilitate intubation and to treat tetanus. In modern anaesthesia, non-depolarising muscle relaxants are nowadays used as successor substances to curare such as atracurium, mivacurium, pancuronium or rocuronium, which have a more favourable active profile. However, the mechanism of action is basically the same as with the active ingredient of curare, tubocurarin.

1. Graefe KH et al. Peripheral muscle relaxants. In: Graefe KH et al (Eds) Pharmacology and Toxicology. Georg Thieme Publisher Stuttgart S.117- 118
2. Roth L et al (1984) Curare. In: Roth L et al. (Eds) Poisonous plants, plant toxins. Nikol Publishing Company Hamburg p.797