Category:Muscle relaxants: Difference between revisions

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"/>

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.

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.