Muscle relaxant
A muscle relaxant is a drug that affects
History
The earliest known use of muscle relaxant drugs was by natives of the
The U.S. Food and Drug Administration (FDA) approved the use of carisoprodol in 1959, metaxalone in August 1962, and cyclobenzaprine in August 1977.[7]
Other skeletal muscle relaxants of that type used around the world come from a number of drug categories and other drugs used primarily for this indication include
Neuromuscular blockers
Muscle relaxation and paralysis can theoretically occur by interrupting function at several sites, including the
and Ca2+
ions to enter the cell and K+
ions to leave the cell, causing a depolarization of the end plate, resulting in muscle contraction.[8] Following depolarization, the acetylcholine molecules are then removed from the end plate region and enzymatically hydrolysed by acetylcholinesterase.[5]
Normal
Spasmolytics
The generation of the
Terminology
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 not every agent in this class has CNS activity (e.g., dantrolene), so this name is inaccurate.[5]
Most sources still use the term "centrally acting muscle relaxant". According to MeSH, dantrolene is usually classified as a centrally acting muscle relaxant.[9] The World Health Organization, in its ATC, uses the term "centrally acting agents",[10] but adds a distinct category of "directly acting agents", for dantrolene.[11] Use of this terminology dates back to at least 1973.[12]
The term "spasmolytic" is also considered a synonym for antispasmodic.[13]
Clinical use
Spasmolytics such as
Muscle relaxants (according to one study) were not advised for
Dantrolene, although thought of primarily as a peripherally acting agent, is associated with CNS effects, whereas baclofen activity is strictly associated with the CNS.Muscle relaxants are thought to be useful in painful disorders based on the theory that pain induces spasm and spasm causes pain. However, considerable evidence contradicts this theory.[17]
In general, muscle relaxants are not approved by
Muscle relaxants such as
Mechanism
Because of the enhancement of inhibition in the CNS, most spasmolytic agents have the side effects of sedation and drowsiness and may cause dependence with long-term use. Several of these agents also have abuse potential, and their prescription is strictly controlled.[22][23][24]
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.[5][25]
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.[26] Neurophysiologic studies show that it depresses excitatory feedback from muscles that would normally increase muscle tone, therefore minimizing spasticity.[27][28] 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.[29]
The
Other common spasmolytic agents include: methocarbamol, carisoprodol, chlorzoxazone, cyclobenzaprine, gabapentin, metaxalone, and orphenadrine.
Thiocolchicoside is a muscle relaxant with anti-inflammatory and analgesic effects and an unknown mechanism of action.[30][31][32][33] It acts as a competitive antagonist at GABAA and glycine receptors with similar potencies, as well as at nicotinic acetylcholine receptors, albeit to a much lesser extent.[34][35] It has powerful proconvulsant activity and should not be used in seizure-prone individuals.[36][37][38]
Side effects
Patients most commonly report
Cyclobenzaprine produces confusion and
Patients taking carisoprodol for a prolonged time have reported dependence, withdrawal and abuse, although most of these cases were reported by patients with addiction history. These effects were also reported by patients who took it in combination with other drugs with abuse potential, and in fewer cases, reports of carisoprodol-associated abuse appeared when used without other drugs with abuse potential.[40]
Common side effects eventually caused by metaxalone include dizziness,
See also
- Benzodiazepine overdose
- Paralysis
- Quaternary ammonium muscle relaxants
- Caroverine
References
- ^ "Definition of Muscle relaxant." MedicineNet.com. (c) 1996–2007. Retrieved on September 19, 2007.
- ^ "muscle relaxant Archived 2013-10-06 at the Wayback Machine." mediLexicon Archived 2013-10-06 at the Wayback Machine. (c) 2007. Retrieved on September 19, 2007.
- ^ "Muscle relaxants." WebMD. Last Updated: February 15, 2006. Retrieved on September 19, 2007.
- ^ "Skeletal Muscle Relaxant (Oral Route, Parenteral Route)." Mayo Clinic. Last Updated: April 1, 2007. Retrieved on September 19, 2007.
- ^ ISBN 0-8385-0565-1.
- PMID 16402115.
- ^ a b "Brief History". Retrieved 2010-07-09.
- ISBN 0-7817-3762-1.
- ^ Dantrolene at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- ^ "M03B Muscle Relaxants, Centrally acting agents". ATC/DDD Index. WHO Collaborating Centre for Drug Statistics Methodology.
- ^ "M03CA01 Dantrolene". ATC/DDD Index. WHO Collaborating Centre for Drug Statistics Methodology.
- PMID 4712630.
- ^ "Dorlands Medical Dictionary:antispasmodic". Archived from the original on 2009-10-01.
- ^ PMID 18711953.
- PMID 17909209.
- ^ PMID 12804507.
- ^ S2CID 24901082.
- S2CID 43152771.
- ^ "When Are Muscle Relaxers Prescribed For Arthritis Patients?". Retrieved 2010-07-09.
- ^ MedlinePlus Encyclopedia: Tension Headache
- ^ "Muscle Relaxants". Retrieved 2010-07-09.
- ISBN 0-443-04483-X.
- ISBN 0-07-112432-2.
- ^ Charney, D.S.; Mihic, J.; Harris, R.A. (2001). "Hypnotics and Sedatives". Goodman & Gilman's. pp. 399–427.
- S2CID 33042651.
- PMID 7970005.
- S2CID 13552923.
- S2CID 21546330.
- PMID 3581584.
- PMID 14563464.
- PMID 19780000.
- PMID 18839644.
- S2CID 20671452.
- S2CID 11390033.
- PMID 17234181.
- S2CID 24017279.
- PMID 19707540.
- S2CID 14308541.
- ^ "Cyclobenzaprine-Oral". Retrieved 2010-07-09.
- ^ "Carisoprodolx". Retrieved 2010-07-09.
- ^ "Side Effects of Metaxalone – for the Consumer". Retrieved 2010-07-09.
- ^ "Precautions". Encyclopedia of Surgery. Retrieved 2010-07-09.
External links
- Skeletal+Muscle+Relaxants at the U.S. National Library of Medicine Medical Subject Headings (MeSH)