Tolperisone (trade name Mydocalm among others) is a centrally acting

skeletal muscle relaxant A muscle relaxant is a drug that affects skeletal muscle function and decreases the muscle tone. It may be used to alleviate symptoms such as muscle spasms, pain, and hyperreflexia. The term "muscle relaxant" is used to refer to two major therapeu ...

used for the treatment of increased muscle tone associated with neurological diseases. It has been used since the 1960s.

Medical uses

Tolperisone is indicated for use in the treatment of pathologically increased tone of the

skeletal muscle Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...

caused by neurological diseases (damage of the

pyramidal tract The pyramidal tracts include both the corticobulbar tract and the corticospinal tract. These are aggregations of efferent nerve fibers from the upper motor neurons that travel from the cerebral cortex and terminate either in the brainstem (''cort ...

multiple sclerosis Multiple (cerebral) sclerosis (MS), also known as encephalomyelitis disseminata or disseminated sclerosis, is the most common demyelinating disease, in which the insulating covers of nerve cells in the brain and spinal cord are damaged. This d ...

myelopathy Myelopathy describes any neurologic deficit related to the spinal cord. The most common form of myelopathy in humans, '' cervical spondylotic myelopathy (CSM)'', also called ''degenerative cervical myelopathy'', results from narrowing of the spina ...

encephalomyelitis Encephalomyelitis is inflammation of the brain and spinal cord. Various types of encephalomyelitis include: * ''Acute disseminated encephalomyelitis'' or ''postinfectious encephalomyelitis'', a demyelinating disease of the brain and spinal cord, p ...

) and of spastic paralysis and other encephalopathies manifested with muscular dystonia. Other possible uses include: *

Spondylosis Spondylosis is the degeneration of the vertebral column from any cause. In the more narrow sense it refers to spinal osteoarthritis, the age-related wear and tear of the spinal column, which is the most common cause of spondylosis. The degenera ...

*Spondylarthrosis *Cervical and lumbar syndromes *

Arthrosis Osteoarthritis (OA) is a type of degenerative joint disease that results from breakdown of joint cartilage and underlying bone which affects 1 in 7 adults in the United States. It is believed to be the fourth leading cause of disability in the w ...

of the large joints * Obliterating atherosclerosis of the extremity vessels *

Diabetic angiopathy Diabetic angiopathy is a form of angiopathy associated with diabetic complications. While not exclusive, the two most common forms are diabetic retinopathy and diabetic nephropathy, whose pathophysiologies are largely identical. Other forms of diab ...

Thromboangiitis obliterans Thromboangiitis obliterans, also known as Buerger disease (English ; ) or Winiwarter-Buerger disease, is a recurring progressive inflammation and thrombosis (clotting) of small and medium arteries and veins of the hands and feet. It is strongly a ...

Raynaud's syndrome Raynaud syndrome, also known as Raynaud's phenomenon, eponymously named after the physician Auguste Gabriel Maurice Raynaud, who first described it in his doctoral thesis in 1862, is a medical condition in which the spasm of small arteries cau ...

Contraindications and cautions

Manufacturers report that tolperisone should not be used in patients with

myasthenia gravis Myasthenia gravis (MG) is a long-term neuromuscular junction disease that leads to varying degrees of skeletal muscle weakness. The most commonly affected muscles are those of the eyes, face, and swallowing. It can result in double vision, dro ...

. Only limited data are available regarding the safety in children, youths, during pregnancy and breastfeeding. It is not known whether tolperisone is excreted into mother's milk. In 2012, following concerns on the safety and efficacy, an "article 31 referral" was triggered at the European Medicines Agency. The European Medicines Agency has recommended restricting the use of tolperisone. After review and a subsequent re-examination in 2012, the Agency concluded the safety and adverse reaction risks of this drug outweigh the benefits, and that there is weak support for its efficacy, in all but one indication (muscle stiffness or spasticity after stroke), and specifically, due to the prevalence of hypersensitivity symptoms such as flushing, rash, severe skin itchiness (with raised lumps), wheezing, difficulty breathing, and swallowing, fast heartbeat and fast decrease in blood pressure (basically anaphylaxis), their recommendations included ceasing advertising in Europe and ceasing injections, updating patient information leaflets, changing to another medicine for existing users, and for prescribers to only use it stroke patients when administered by mouth, not injection.

Side effects

Adverse effects occur in fewer than 1% of patients and include muscle weakness, headache, arterial

hypotension Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the dias ...

, nausea, vomiting,

dyspepsia Indigestion, also known as dyspepsia or upset stomach, is a condition of impaired digestion. Symptoms may include upper abdominal fullness, heartburn, nausea, belching, or upper abdominal pain. People may also experience feeling full earlier t ...

, and dry mouth. All effects are reversible. Allergic reactions occur in fewer than 0.1% of patient and include skin rash,

hives Hives, also known as urticaria, is a kind of skin rash with red, raised, itchy bumps. Hives may burn or sting. The patches of rash may appear on different body parts, with variable duration from minutes to days, and does not leave any long-lasti ...

Quincke's edema Angioedema is an area of swelling ( edema) of the lower layer of skin and tissue just under the skin or mucous membranes. The swelling may occur in the face, tongue, larynx, abdomen, or arms and legs. Often it is associated with hives, which ...

, and in some cases

anaphylactic shock Anaphylaxis is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of use of emergency medication on site. It typically causes more than one of the follow ...

Overdose

Excitability has been noted after ingestion of high doses by children. In suicide studies of three isolated cases, it is believed that ingestion of tolperisone was the cause of death.

Interactions

Tolperisone does not have a significant potential for interactions with other pharmaceutical drugs. It cannot be excluded that combination with other centrally acting muscle relaxants,

benzodiazepine Benzodiazepines (BZD, BDZ, BZs), sometimes called "benzos", are a class of depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat conditions such as anxiety disorders, ...

s or

nonsteroidal anti-inflammatory drug Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration of ...

s (NSAIDs) may make a dose reduction necessary in some patients.

Pharmacology

Mechanism of action

Tolperisone is a centrally acting muscle relaxant that acts at the

reticular formation The reticular formation is a set of interconnected nuclei that are located throughout the brainstem. It is not anatomically well defined, because it includes neurons located in different parts of the brain. The neurons of the reticular formation ...

in the brain stem by blocking voltage-gated sodium and

calcium channels A calcium channel is an ion channel which shows selective permeability to calcium ions. It is sometimes synonymous with voltage-gated calcium channel, although there are also ligand-gated calcium channels. Comparison tables The following tables ex ...

Pharmacokinetics

Tolperisone is absorbed nearly completely from the gut and reaches its

peak Peak or The Peak may refer to: Basic meanings Geology * Mountain peak ** Pyramidal peak, a mountaintop that has been sculpted by erosion to form a point Mathematics * Peak hour or rush hour, in traffic congestion * Peak (geometry), an (''n''-3)-di ...

blood plasma concentration after 1.5 hours. It is extensively metabolised in the liver and kidneys. The substance is excreted via the kidneys in two phases; the first with a half-life of two hours, and the second with a half-life of 12 hours.

Chemistry

Tolperisone a

piperidine Piperidine is an organic compound with the molecular formula (CH2)5NH. This heterocyclic compound, heterocyclic amine consists of a six-membered ring containing five methylene bridges (–CH2–) and one amine bridge (–NH–). It is a colorless ...

derivative.

Society and culture

Brand names

Brand names include ''Mydocalm'', ''Biocalm'', ''Mydeton'', ''Miderizone'', ''Mydoflex'', ''Myolax'', ''Myoxan'' and ''Viveo''.

References

{{Channel blockers 1-Piperidinyl compounds Muscle relaxants Aromatic ketones Calcium channel blockers Sodium channel blockers