Muscle Relaxants

Skeletal Muscle relaxants


  • Peripherally acting (Neuromuscular blockers)
  • Pre synaptic neuromuscular blocker
  • Inhibit Ach synthesis: triethylacholine – hemicholinium
  • Inhibit Ach release: Mg, aminoglycosides, botulinum toxin
  • Post synaptic neuromuscular blocker

Competitive (non depolarizing blockers):

d- tubocurarine
Depolarizing blockers: succinylcholine (suxamethonium)
Centrally acting skeletal muscle relaxants
Baclofen – Diazepam
Direct acting skeletal muscle relaxants

Mechanism of action

Non depolarizing relaxant drugs
All neuromuscular blocking agents used in USA except succinylcholine are classifies as non depolarizing agents
When small doses of nondepolarizing muscle relaxants are administered, they act predominantly at nicotinic receptor site by competing with acetylcholine.
The least potent relaxant (eg. Rocuronium) have the fastest onset and the shortest duration of action
In large doses, nondepolarizing drugs enter the pore of ion channel to produce a more intense motor blockade. This action further weakens neuromuscular transmission and diminishes the ability of the cholinesterase inhibitor (eg. Neostigmine, edrophonium, pyridostigmine) to antagonize the effect of non depolarizing muscle relaxants.
They also block prejunctional sodium channels. As a result of this action, muscle relaxants interfere with the metabolization of acetylcholine at the nerve ending. Both halothane and succinylcholine increase the intensity and duration of action of pancuronium. (1)

Depolarizing relaxant drugs

Phase I block (depolarizing)
Succinylcholine is the only available depolarizing neuromuscular blocking drug. (2)
It produces a longer effect at the myoneural junction. It reacts with the nicotinic receptor to open the channel and cause depolarization of the motor end plate, and this in turn spreads to the adjacent membranes, causing contractions of muscle motor units. Because succinylcholine is not metabolized at the synapse, the depolarized membranes remain depolarized and unresponsive to subsequent impulses. This is called Phase I (depolarizing) block, not reversed by cholinesterase inhibitors

Phase II block (desensitizing)

With prolonged exposure to succinylcholine, initial end plate depolarization decreases and the membrane become repolarized. Despite this repolarization, the membrane cannot be easily depolarized again because it is desensitized
The channel block is more important than agonist action at the receptor in phase II of succinylcholine’s neuromuscular blocking action. Later in phase II, the characteristics of the blockade are nearly identical to those of a non depolarizing block (ie, a nonsustained twitch response to a titanic stimulus) with possible reversal by acetylcholinesterase inhibitors.Succinylcholine produce reversible contracture of intrafusal fibers of the muscle spindle and leads to acceleration of the afferent discharge. (3) Another study by Martin Jeevendra and Duriex Marcel E found that: (4)
1. Succinylcholine caused initial activation of the muscle AchR followed by desensitization

          2. At clinically relevant concentrations, succinylcholine has no stimulatory or inhibitory interactions                            with α3β2 (presynaptic) or α3β4 (ganglionic) AchRs

          3. High doses of succinylcholine caused inhibition of both α3β2 and α3β4 receptor. 

Pharmacokinetics of neuromuscular blocking drugs

Succinylcholine has the fastest onset of action among all the muscle relaxants. (5)
The elimination of succinylcholine appears to follow first order kinetics with linear relationship between intensity of the effect and logarithm of the dose. The rate of recovery is independent of dose for each age group. The rate of recovery is faster in children than in infants; the rate of recovery is faster in infants than in adults. The elimination rate constant for infabts was similar to that of children, but is dissimilar from those of adults. (6)

DrugEliminationClearance (mL/kg/minApproximate duration of action (minutes)Approximate potency relative to Tubocurarine
CisatracuriumMostly spontaneous5-625-441.5
MivacuriumPlasma ChE
TubocurarineKidney (40%)2.3-2.4>501
PancuroniumKidney (80%)1.7-1.8>356
PipecuroniumKidney (60%) and liver2.5-3.0>356
RocuroniumLiver (75-90%) and kidney2.925-350.8
VecuroniumLiver (75-90%) and kidney3-5.325-356
SuccinylcholinePlasma ChE (100%)
Source: Bertram G. Katzung, Susan B. Masters and Anthony J. Trevor. Basic and Clinical Pharmacology. 11th Edition. Chapter 27. Skeletal Muscle Relaxants. Page 451-465.

Pharmacology of Neuromuscular blocking drugs


ED95a (mg/kg)

Intubating dose (mg/kg)

Onset timeb (s)

Clinical durationc (min)


























































a: The dose that depresses the twitch height by 95%

b: time to 95% depression of first twitch of train-of-four

c: time to 25% recovery of first twitch of train-of-four

d: This is about three times the ED95

Source: Jonnas Appiah-Ankam, Jennifer M Hunter. Pharmacology of neuromuscular blocking drugs. Contin Educ Anaesth Crit Care Pain. 2004;4(1):2-7. 

Side effects of succinylcholine: (2)

Cardiovascular effects: bradycardia. It can cause arrhythmias when administered with halothane anesthesia
Muscle pain: experienced the day after surgery and is worse in ambulatory patients. It is more common in the young and healthy with a large muscle mass. The pain is thought to be a result of the initial fasciculations and occurs in unusual sites, such as the diaphragm, intercostal muscles and between the scapulae.
Hyperkalemia: Administration of succinylcholine 1.0 mg kg−1 produces a small increase (∼0.5 mmol litre−1) in serum potassium concentration in patients undergoing halothane anaesthesia.
Malignant hyperthermia: Succinylcholine is a recognized trigger factor for malignant hyperthermia and may also precipitate muscle contracture in patients with myotonic dystrophies.
Hypersensitivity: Succinylcholine accounts for about 50% of hypersensitivity reactions to NMBDs. The incidence is estimated to be 1 in 4000 administrations.
Increased intraocular pressure: The average increase in intra-ocular pressure after succinylcholine 1.0 mg kg−1 is 4–8 mm Hg. The increase occurs promptly after intravenous injection, peaking at 1–2 min and lasting as long as the neuromuscular block.
Increased intragastric pressure:
This complication is likely to occur in patients with delayed gastric emptying (those with diabetes), traumatic injury, esophageal dysfunction and morbid obesity.
Prolonged paralysis: Reduced plasma cholinesterase activity, a result of inherited or acquired factors, may alter the duration of action of succinylcholine, leading to prolonged paralysis.

Effects of muscle relaxants:

Vecuronium, pipecuronium, doxacurium, cisatracurium and rocuronium all have minimal cardiovascular effects
Pancuronium, atracurium and mivacurium produce cardiovascular effects that are mediated by either autonomic or histamine receptors
Tubocurarine and to lesser extent metocurine, mivacuronium and atracurium can produce hypotension as a result of histamine release
With larger doses, ganglionic blockade may occur with tubocurarine and metocurine
Pancuronium causes a moderate increase in heart rate and a smaller increase in cardiac output, with little or no change in systemic vascular resistance
Pancuronium induced tachycardia is primarily due to vagolytic action, release of norepinephrine from adrenergic nerve endings and blockade of neuronal uptake of norepinephrine may be secondary mechanisms

DrugEffect on autonomic gangliaEffect on cardiac muscarinic receptorsTendency to cause histamine release
MetocurineWeak blockNoneSlight
TubocurarineWeak blockNoneModerate
PancuroniumNoneModerate blockNone
GallamineNoneStrong blockNone
Source: Bertram G. Katzung, Susan B. Masters and Anthony J. Trevor. Basic amd Clinical Pharmacology. 11th Edition. Chapter 27. Skeletal Muscle Relaxants. Page 451-465.

Interactions with other drugs

  1. Anesthetics
    • Inhaled anesthetic potentiate the neuromuscular blockade produced by non depolarizing muscle relaxants in dose dependent fashion
    • Inhaled anesthetic augment the effect of muscle relaxants in the following order:

Isoflurane (most); sevoflurane, desflurane, enflurane and halothane; nitrous oxide (least)

  • Rare interaction of succinylcholine with volatile anesthetics results in malignant hyperthermia
  • Isobolographic and fractional analysis of the suxamethonium-mivacurium and suxamethonium-atracurium combinations demonstrated antagonistic interactions. (7)
  • The recovery from the effects of one nondepolarizing muscle relaxant given after partial recovery from another, more resembles the recovery from the muscle relaxant given first. (8)
  • Antibiotics
    • Neuromuscular blockade is enhanced by antibiotics (eg. aminoglycosides)
    • For patients treated with gentamycin and tobramycin, atracurium offers advantage over vecuronium when prolonged block is not desired. (9) 
    • Many antibiotics have shown to cause a depression of evoked release of acetylcholine similar to that caused by administering magnesium. The mechanism of this prejunctional effect appears to be blockade of specific P-type calcium channels in the motor nerve terminal
  • Antiarrhythmic drugs and local anesthetics
    • The antiarrhythmics lidocaine, procainamide, propanolol and diphenylhydantoin increase the intensity and duration of d-Tubocurarine neuromuscular blockade. (10) 
    • Higher concentrations of bupivacaine have been associated with cardiac arrhythmias independent of the muscle relaxant used.
    • In small doses, local anesthetics can depress posttetanic potentiation via a prejunctional neural effect.
    • In large doses, local anesthetics can block neuromuscular transmission
    • With higher doses, local anesthetics block acetylcholine- induced muscle contractions as a result of blockade of the nicotinic receptor ion channels
    • Neuromuscular blocking agents potentiate the action of local anesthetics by acting on different sites of the neuromuscular junction. The block caused by combination of local anesthetic and neuromuscular blocking agent can be reversed by 4-aminopyridine. (11)
  • Other neuromuscular blocking drugs
    • The end plate depolarizing effect of succinylcholine can be antagonized by administering a small dose of non depolarizing blocker
    • To prevent the fasciculation associated with succinylcholine administration, a small non paralyzing dose of a nondepolarizing drug can be given before succinylcholine (eg. d-tubourarine, 2 mg IV, or pancuronium, 0.5 mg iv)
  • Lithium: Lithium enhances the myoneural blocking effects of suxamethonium, pancuronium and vecuronium. (12)

Reversal of nondepolarizing neuromuscular blockade

  • The cholinesterase inhibitors effectively antagonize the neuromuscular blockade caused by nondepolarizing drugs
  • Neostigmine and pyridostigmine antagonize the nondepolarizing neuromuscular blockade by increasing the availability of acetylcholine at the motor end plate, mainly by inhibition of acetylcholinesterase
  • Edrophonium antagonized the neuromuscular blockade purely by inhibiting acetylcholinesterase activity. Edrophonium has a more rapid onset of action but may be less effective than neostigmine in reversing the effects of nondepolarizing blockers in the presence of a profound degree of neuromuscular blockade.
  • A novel cyclodextrin reversal drug, sugammadex, has been submitted for FDA approval. It can rapidly inactivate steroidal neuromuscularblocking drugs by forming an inactive complex, which is excreted in the urine.


  1. Katz Ronald L. Modification of the action of pancuronium by succinylcholine and halothane. Anesthesiology December 1971;35(6). 
  2. Jonnas Appiah-Ankam, Jennifer M Hunter. Pharmacology of neuromuscular blocking drugs. Contin Educ Anaesth Crit Care Pain. 2004;4(1):2-7. 
  3. Cedric M Smith, Earl Eldred. Mode of action of succinylcholine on sensory endings of mammalian muscle spindles. JPET February 1961;131(2):237-242.
  4. Martyn Jeevendra, Durieux Marcel E. Succinylcholine: New insights into mechanism of action of old drug. Anesthesiology April 2006;104(4):633-634. 
  5. Sluga M, Ummenhofer W, Studer W, Seigemund M, Marsch SC. Rocuronium versus succinylcholine for rapid sequence induction of anesthesia and endotracheal intubation: A prospective, randomized trial in emergent cases. Anesth Analg 2005;101:1356-61. 
  6. Cook DR, Wingard LB, Taylor FH. Pharmacokinetics of succinylcholine in infants, children and adults. Clinical Pharmacology and Therapeutics. 1976;20(4):493-498. 
  7. KS Kim, DJ Na, SU Chon. Interactions between suxamethonium and mivacurium or atracurium. British Journal of Anesthesia. 1996;77:612-616. 
  8. Harrop-Griffiths AW, Hood JR. Interactions between non depolarizing muscle relaxants. Anesthesiology 1997;86(1):263. 
  9. JY Dupuis, R Martin, JP Tetrault. Atracurium and vecuronium interaction with gentamycin and tobramycin. Can J Anaesth. 1989;36(4):407-11. 
  10. Katzung BG, Walter M, Harrah Marvin D. The interactions of d-Tubocurarine with Antiarrhythmic drugs. Anesthesiology October 1970;33(4). 
  11. Matsuo S, Rao DBS, Chaudry I, Foldes FF. Interaction of muscle relaxant and local anesthetics at the neuromuscular junction. Anesthesia & Analgesia. September/October 1978;57(5). 
  12. Saarnivaara L, Ertama P. Interactions between lithium/rubidium and six muscle relaxants. A study on the rat phrenic nerve-hemidiaphragm preperation. Des Anaesthesist. 1992;41(12):760-764.