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This article refers to skeletal muscle relaxants. For information on smooth muscle relaxants, see Antispasmodic.

A muscle relaxant is a drug which affects skeletal muscle function and decreases the muscle tone. They may be used to alleviate symptoms such as muscle spasm and pain, and hyperreflexia. The term "muscle relaxant" is used to refer to two major therapeutic groups: neuromuscular blockers and spasmolytics. Neuromuscular blockers act by interfering with transmission at the neuromuscular end plate and have no CNS activity. They are often used during surgical procedures and in intensive care and emergency medicine to cause paralysis. Spasmolytics, also known as "centrally-acting" muscle relaxants, are used to alleviate musculoskeletal pain and spasms and to reduce spasticity in a variety of neurologic conditions. While both neuromuscular blockers and spasmolytics are often grouped together as muscle relaxants,[1][2] common everyday language usually implies that the use of the term refers to spasmolytics only.[3][4]


The earliest known use of muscle relaxant drugs dates back to the 16th century, when European explorers encountered natives of the Amazon Basin in South America using poison-tipped arrows that produced death by skeletal muscle paralysis. This poison, known today as curare, led to some of the earliest scientific studies in pharmacology. Its active ingredient, tubocurarine, as well as many synthetic derivatives, played a significant role in scientific experiments to determine the function of acetylcholine in neuromuscular transmission.[5] By 1943, neuromuscular blocking drugs became established as muscle relaxants in the practice of anesthesia and surgery.[6]

Neuromuscular-blocking drugs

Detailed view of a neuromuscular junction:
1. Presynaptic terminal
2. Sarcolemma
3. Synaptic vesicle
4. Nicotinic acetylcholine receptor
5. Mitochondrion

Muscle relaxation and paralysis can theoretically occur by interrupting function at several sites, including the central nervous system, myelinated somatic nerves, unmyelinated motor nerve terminals, nicotinic acetylcholine receptors, the motor end plate, and the muscle membrane or contractile apparatus. Most neuromuscular blockers function by blocking transmission at the end plate of the neuromuscular junction. Normally, a nerve impulse arrives at the motor nerve terminal, initiating an influx of calcium ions which causes the releases of acetylcholine. Acetylcholine then diffuses across the synaptic cleft to the nicotinic receptors located on the motor end plate. The combination of two acetylcholine molecules results in the opening of the sodium-potassium channel of the nicotinic receptor, causing a depolarization of the end plate, resulting in muscle contraction. Following depolarization, the acetylcholine molecules are then removed from the end plate region and enzymaticaly destructed by acetylcholinesterase.[5]

Normal end plate function can be blocked by two mechanisms. Nondepolarizing agents like tubocurarine block the agonist, acetylcholine, from activating nicotinic receptors, thereby preventing depolarization. Alternatively, depolarizing agents such as succinylcholine are nicotinic receptor agonists and block muscle contraction by depolarizing the muscle to such an extent that it can no longer initiate an action potential and contract.[5]

All neuromuscular blocking drugs are structurally similar to acetylcholine, the endogenous ligand, in many cases containing two acetylcholine molecules linked end-to-end by a rigid carbon ring system, as in pancuronium.[5]

Chemical diagram of pancuronium, with red lines indicating the two acetylcholine "molecules" in the structure.


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A view of the spinal cord and skeletal muscle showing the action of various muscle relaxants. Black lines ending in arrow heads represent chemicals or actions that enhance the target of the lines. Blue lines ending in squares represent chemicals or actions that inhibition the target of the line. Click image to enlarge diagram.

The generation of the neuronal signals in motor neurons that cause muscle contractions are dependent on the balance of synaptic excitation and inhibition that the motor neuron receives. Spasmolytic agents generally work by either enhancing the level of inhibition, or reducing the level of excitation. Inhibition is enhanced by mimicking or enhancing the actions of endogenous inhibitory substances, such as GABA. Because they may act at the level of the cortex, brain stem or spinal cord, or all three areas, they have traditionally been referred to as "centrally-acting" muscle relaxants. However, it is now known that not every agent in this class has CNS activity (e.g. dantrolene), so this name is inaccurate.[5]

Because of the enhancement of inhibition in the CNS, most spasmolytic agents have the side-effects of sedation, drowsiness and may cause dependence with long term use. Several of these agents also have abuse potential, and their prescription is strictly controlled.[7][8][9]

The benzodiazepines, such as diazepam, interact with the GABAA receptor in the central nervous system. While it can be used in patients with muscle spasm of almost any origin, it produces sedation in most individuals at the doses required to reduce muscle tone.[5]

Baclofen is considered to be at least as effective as diazepam in reducing spasticity, and causes much less sedation. It acts as a GABA agonist at GABAB receptors in the brain and spinal cord, resulting in hyperpolarization of neurons expressing this receptor, most likely due to increased potassium ion conductance. Baclofen also inhibits neural function presynaptically, by reducing calcium ion influx, and thereby reducing the release of excitatory neurotransmitters in both the brain and spinal cord. It may also reduce pain in patients by inhibiting the release of substance P in the spinal cord as well.[10][5]

Clonidine and other imidazoline compounds have also been shown to reduce muscle spasms by their central nervous system activity. Tizanidine is perhaps the most thoroughly studied clonidine analog, and is an agonist at α2-adrenergic receptors, but reduces spasticity at doses that result in significantly less hypotension than clonidine.[11] Neurophysiologic studies show that it depresses excitatory feedback from muscles that would normally increas muscle tone, therefore minimising spacticity.[12][13] Furthermore, several clinical trials indicate that tizanidine has a similar efficacy to other spasmolytic agents, such as diazepam and baclofen, with a different spectrum of adverse effects.[14]

The hydantoin-derivative dantrolene is a spasmolytic agent with a unique mechanism of action outside of the CNS. Dantrolene reduces skeletal muscle strength by inhibiting the excitation-contraction coupling in the muscle fiber. In normal muscle contraction, calcium is released from the sarcoplasmic reticulum through the ryanodine receptor channel, which causes the tension-generating interaction of actin and myosin. Dantrolene interferes with the release of calcium by binding to the ryanodine receptor and blocking the endogenous ligand ryanodine by competitive inhibition. Muscle that contracts more rapidly is more sensitive to dantrolene than muscle that contracts slowly, although cardiac muscle and smooth muscle are depressed only slightly, most likely because the release of calcium by their sarcoplasmic reticulum involves a slightly different process. Major adverse effects of dantrolene include general muscle weakness, sedation, and occasionally hepatitis.[5]

Other common spasmolytic agents include: methocarbamol, carisoprodol, chlorzoxazone, cyclobenzaprine, gabapentin, metaxalone, and orphenadrine.

See also


  1. "Definition of Muscle relaxant." (c) 1996-2007. Retrieved on September 19, 2007.
  2. "muscle relaxant." mediLexicon. (c) 2007. Retrieved on September 19, 2007.
  3. "Muscle relaxants." WebMD. Last Updated: February 15, 2006. Retrieved on September 19, 2007.
  4. "Skeletal Muscle Relaxant (Oral Route, Parenteral Route)." Mayo Clinic. Last Updated: April 1, 2007. Retrieved on September 19, 2007.
  5. 5.0 5.1 5.2 5.3 5.4 5.5 5.6 5.7 Miller, R.D. "Skeletal Muscle Relaxants," in, "Basic & Clinical Pharmacology: Seventh Edition," by Bertram G. Katzung. Published by Appleton & Lange, 1998, p.434-449. ISBN 0838505651
  6. Bowman, W.C. "Neuromuscular block." Br. J. Pharmacol. January 2006. Vol. 147, Suppl. S277-86. PMID: 16402115
  7. Rang, H.P. & Dale, M. M "Drugs Used in Treating Motor Disorders" in, "Pharmacology 2nd Edition" Published by Churchill Livingston London, 1991, p.684-705.
  8. Standaert, D.G. & Young, A. B "Treatment Of Central Nervous System Degerative Disorders" in, "Goodman & Gilman's The Pharmacological Basis of Therapeutics 10th Edition" by Hardman, J.G. & Limbird, L.E. Published by McGraw Hill, 2001, p.550-568.
  9. Charney, D.S., Mihic, J. & Harris, R.A. "Hypnotics and Sedatives" in, "Goodman & Gilman's The Pharmacological Basis of Therapeutics 10th Edition" by Hardman, J.G. & Limbird, L.E. Published by McGraw Hill, 2001, p.399-427.
  10. Cazalets JR, Bertrand S, Sqalli-Houssaini Y, Clarac F (1998). "GABAergic control of spinal locomotor networks in the neonatal rat". Ann. N. Y. Acad. Sci. 860: 168–80. PMID 9928310.
  11. Young, R.R. (editor). "Symposium: Role of tizanidine in the treatment of spasticity." Neurology. 1994, Vol. 44 (Suppl. 9), p. 1.
  12. Bras H, Jankowska E, Noga B, Skoog B (1990). "Comparison of Effects of Various Types of NA and 5-HT Agonists on Transmission from Group II Muscle Afferents in the Cat". 2 (12): 1029–1039. PMID 12106064.
  13. Jankowska E, Hammar I, Chojnicka B, Hedén CH (2000). "Effects of monoamines on interneurons in four spinal reflex pathways from group I and/or group II muscle afferents". Eur. J. Neurosci. 12 (2): 701–14. PMID 10712650.
  14. Young, R.R; Weigner, A.W. "Spasticity." Clin. Orthop. 1987, Vol. 219, p. 50.

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