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The term "muscle relaxant" covers two quite different kinds of medicine, united only by name and by the broad effect of reducing muscle activity. The first are the '''neuromuscular blocking agents''', which paralyse skeletal muscle and are used to hold a patient still during surgery. The second are the '''skeletal muscle relaxants''' proper — the medicines prescribed for muscle spasm and spasticity, taken by mouth and used outside the operating room. The two classes act in different places, by different mechanisms, and for different purposes; this page treats their histories in turn.

== Curare and the neuromuscular blocking agents ==
The story of the neuromuscular blockers begins not in medicine but in the forests of South America, where indigenous peoples prepared arrow and dart poisons known collectively as curare. A creature struck by a curare-tipped dart is paralysed and dies of asphyxiation, while — as later investigators found — remaining conscious. European explorers reported the poison from the sixteenth century onward; Sir Walter Raleigh described poisoned arrows after his travels in the 1590s, and naturalists including Charles Waterton later carried samples back to Europe.<ref name="bowman">Bowman WC. Neuromuscular block. ''Br J Pharmacol.'' 2006;147(Suppl 1):S277–S286. PMID 16402115.</ref>

In the early nineteenth century, experiments by Benjamin Brodie and others established a crucial fact: an animal poisoned with curare need not die — if its breathing is maintained artificially, it can recover completely. The poison stopped the muscles, not the heart or the mind.<ref name="bowman"/> In the mid-nineteenth century the French physiologist Claude Bernard localized curare's action to the junction between nerve and muscle — the neuromuscular junction — showing that it interrupts the signal from nerve to muscle rather than acting on either alone.<ref name="bowman"/>

Despite this understanding, curare had almost no medical use for roughly a century. That changed in 1942, when the anesthetists Harold Griffith and Enid Johnson administered a curare preparation to a patient during an operation in Montreal, deliberately using it to relax the muscles.<ref name="statpearls">Neuromuscular blocking agents. ''StatPearls.'' NCBI Bookshelf; 2024.</ref> This is generally regarded as the beginning of the modern use of neuromuscular blocking agents in anesthesia. It changed the nature of anesthesia itself: where surgery had previously required dangerously deep anesthesia to keep a patient still, muscle relaxation could now be produced separately, and modern general anesthesia came to be understood as a combination of hypnosis, analgesia, and muscle relaxation.<ref name="statpearls"/> Curare's active alkaloid, tubocurarine, was followed by a series of synthetic agents — gallamine, succinylcholine, pancuronium, vecuronium, atracurium, rocuronium — and the crude plant extract is now of historical interest only.<ref name="statpearls"/>

== Mephenesin, meprobamate, and the skeletal muscle relaxants ==
The medicines that most people mean by "muscle relaxant" — those taken for back pain or muscle spasm — have a separate history, and it begins, unexpectedly, with a search for a way to preserve penicillin. In the 1940s the researcher Frank Berger, testing compounds for antibacterial activity, found that one of them, mephenesin (originally called myanesin), relaxed laboratory animals without putting them to sleep.<ref name="berger">Berger FM, Bradley W. The pharmacological properties of α:β-dihydroxy-γ-(2-methylphenoxy)-propane (myanesin). ''Br J Pharmacol Chemother.'' 1946;1(4):265–272. PMID 20279248. See also Balon R. The dawn of anxiolytics: Frank M. Berger, 1913–2008. ''Am J Psychiatry.'' 2008;165(12):1531. PMID 19047334.</ref> Mephenesin had drawbacks — chiefly a very short duration of action — and Berger and the chemist Bernard Ludwig set out to find a longer-lasting relative. The result, synthesized in 1950, was meprobamate.<ref name="berger"/>

Meprobamate had a notable second career. Marketed from 1955 as Miltown, it became one of the first blockbuster psychiatric medicines, widely prescribed as a "tranquilizer" for anxiety — a reminder that the line between a muscle relaxant and a sedative is not sharp, since much of this class works by depressing the central nervous system. The carbamate muscle relaxant carisoprodol is chemically related to meprobamate and is in fact metabolized to it in the body.<ref name="ncbi-smr">Drug class review: skeletal muscle relaxants. NCBI Bookshelf.</ref>

Over the following decades a range of further oral muscle relaxants came into use, including methocarbamol, cyclobenzaprine — which is structurally related to the tricyclic antidepressants — metaxalone, chlorzoxazone, and orphenadrine. A separate group is used specifically for spasticity (the sustained muscle tightness seen in conditions such as multiple sclerosis, spinal cord injury, and cerebral palsy): baclofen, tizanidine, and dantrolene.<ref name="ncbi-smr"/>

== Mechanisms ==
The two families do not share a mechanism. The neuromuscular blocking agents act at the neuromuscular junction, the synapse between motor nerve and skeletal muscle, where they interfere with the action of the neurotransmitter acetylcholine; the result is paralysis of skeletal muscle. The skeletal muscle relaxants are more varied. Most of the agents used for musculoskeletal pain are described as centrally acting — understood to reduce muscle activity through effects on the brain and spinal cord rather than on muscle directly, though for several of them the mechanism is not well established and sedation may account for much of the effect. Among the antispasticity drugs, baclofen acts as an agonist at GABA-B receptors, tizanidine at α2-adrenergic receptors, and dantrolene acts directly on skeletal muscle, reducing the release of calcium required for contraction.<ref name="ncbi-smr"/> That these agents bind these targets is established; the fuller relationship between target and clinical effect varies by agent and, for the centrally acting group in particular, remains incompletely understood.

== Members ==
'''Neuromuscular blocking agents''' (used in anesthesia) include [[tubocurarine]], [[succinylcholine]], [[pancuronium]], [[vecuronium]], [[atracurium]], and [[rocuronium]].

'''Skeletal muscle relaxants''' used for musculoskeletal pain include [[cyclobenzaprine]], [[methocarbamol]], [[carisoprodol]], [[metaxalone]], [[chlorzoxazone]], and [[orphenadrine]]; those used for spasticity include [[baclofen]], [[tizanidine]], and [[dantrolene]]. [[Meprobamate]] and the [[benzodiazepines]] also have muscle-relaxant activity. The lists are not exhaustive.

== Safety ==
The neuromuscular blocking agents are given only where breathing can be supported artificially: by paralysing skeletal muscle they also paralyse the muscles of respiration, and a person under their effect cannot breathe unaided. Used in anesthesia, they also carry the risk of anesthesia awareness — a patient conscious but unable to move or signal — if muscle relaxation is not matched by adequate hypnosis.

The oral skeletal muscle relaxants most commonly cause drowsiness and other effects of central nervous system depression; this is the basis of concern about their use while driving, and about combining them with alcohol or other sedatives. Several are considered poorly suited to older adults, in whom they are associated with falls and fractures. Carisoprodol in particular carries a recognized risk of dependence, linked to its metabolism to meprobamate. Abrupt discontinuation of baclofen can produce a withdrawal syndrome and is generally avoided. Figures for these risks are population estimates that vary between studies, and individual response varies considerably between people.

== References ==

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