The high prevalence of anxiety-related problems means that different disciplines are seeking to develop different ways of addressing them. Among them we can find pharmacology, which throughout history has been discovering and developing different substances that allow to treat this type of problems.

Many are highly effective, although some of them and especially the first generations of anti-anxiety drugs have shown that they can also cause dangerous side effects. In some cases, the drug has even been recommended and eventually withdrawn in most parts of the world. A relatively recent case is that of meprobamate, which we will discuss throughout this article .

What is meprobamate?

The name meprobamate refers to an anxiolytic or tranquilizing drug , which through its action on the body generates relief from anxiety and agitation. Among the anxiolytics, it belongs to the group of propanedioles and carbomates.

It is one of the oldest types of tranquilizers or anxiolytic drugs, born in 1950 and applied as a psychoactive drug since 1955. It replaced the barbiturates (with which it shares properties at a pharmacological level), but with the arrival of the benzodiazepines its use decreased to a great extent to that substituted by these.

This drug has myorelaxant, hypnotic and sedative effects, and its effectiveness and half-life is between six and seventeen hours (although there may be accumulation and prolongation of this in excessively long treatments), similar to that of intermediate-acting barbiturates. Its use is usually reserved for the short-term treatment of anxiety, since this substance has a high addictive potential and dangerous side effects. It is metabolised in the liver and excreted by the kidneys, and comes in tablet, capsule and solution form for oral and intravenous administration.

But while it has a certain level of effectiveness, it also has a very narrow margin of safety between therapeutic and toxic doses, making it relatively easy to suffer an unintentional overdose that can lead to serious repercussions and even death. For this reason, and given the existence of much safer therapeutic alternatives in 2012, the European Union’s Medicines Agency recommended its withdrawal, and it is now being withdrawn from much of the globe.

Mechanism of action of this psychoactive drug

Meprobamate acts in the body by changing the way the nervous system functions, although the way it does so is generally not well known. It is a drug that inhibits nerve function and reduces neuronal activation and activity in different brain nuclei .

Thus, it is known that it acts by causing depression in the central nervous system of nuclei such as the limbic system and the thalamus (something that contributes to decrease anxiety), besides also affecting the spinal cord (something that is related to its action as a muscle relaxant) affecting among others the interneurons that connect the different neurons that are part of the motor system.

What are your indications?

As a sedative-hypnotic anxiolytic, meprobamate was mainly indicated for the short-term treatment of symptoms of anxiety and nervous agitation .

In addition, another common indication for this drug has been the treatment of conditions linked to spasticity and muscular rigidity, given that, as we have said, it has positive effects on the relaxation of the muscles. Although it is not among its indications, it has anticonvulsive effects, which can help to control seizures typical of different disorders.

It also had as an indication the treatment of primary insomnia , but in this aspect its efficacy is rather limited. Last but not least, it should be noted that it has been used for the treatment of conditions such as arterial hypertension, given that it has a strong effect on their reduction.

Side effects

Meprobamate is a drug that may have some effectiveness, but its use may have a significant risk of generating unpleasant and even dangerous side effects, to the point that it has been withdrawn from many countries because of its poor safety.

Some relatively frequent side effects are sedation, feeling of fatigue, headache, dizziness and lack of motor coordination . Vomiting and diarrhoea are also possible, as well as anorexia or loss of appetite. Others that are more serious and require medical attention are unexplained bleeding, problems and decreased ability to breathe and communicate, tachycardia and arrhythmia.

It should also be noted that it causes hypotension, which, although it has been used medically, can be problematic and dangerous depending on the sector of the population. It can also cause cognitive impairment and episodes of confusion, urticaria, angioneurotic edema, bronchospasm or difficulty in urination. It can also cause blood problems, including anemia, agranulocytosis, leukopenia and thrombocytopenia.

Among these side effects stands out its addictive potential, something that it shares to a great extent with barbiturates and that can lead to physical and psychological dependence on this substance and to abusive use, as well as withdrawal symptoms after cessation that can lead to convulsions, hallucinations, anxiety, vomiting, loss of appetite and lethargy. In case of overdose it can even lead to fatal respiratory arrest or entry into a coma.

Contraindications

Although this is a withdrawn drug, it is also interesting to know which sectors of the population are particularly contraindicated, given that in some cases its consumption is dangerous and increases the probability of suffering serious medical problems.

It is primarily contraindicated for people who are allergic to this drug or its components or to drugs from the carbamate group. It is also contraindicated for those with basic arterial hypotension, as well as for those suffering from liver or kidney failure or insufficiency or for those suffering from porphyria (it may worsen this condition). In epileptic patients it can even lead to seizures.

It is contraindicated (except when necessary) in pregnant and lactating women, since the drug is capable of crossing the placenta or of being transmitted through breast milk and is capable of causing anomalies. Caution should be exercised by patients with diabetes, the elderly and children, subjects with depression and a history of suicide attempts are also contraindicated, as are people with a history of substance dependence. It should not be mixed with alcohol or other depressant substances, as well as antidepressants, muscle relaxants, anticonvulsants or narcotics, among others.

Bibliographic references:

  • American Society of Health-System Pharmacist (2017). Meprobamate. MedlinePlus [Online]. Available at: https://medlineplus.gov/spanish/druginfo/meds/a682077-es.html#special-dietary.
  • European Medicines Agency (2012). Questions and answers on the suspension of marketing authorisations for medicinal products containing meprobamate for oral use. Outcome of a procedure pursuant to Article 107 of Directive 2001/83/EC Online]. Available at: https://www.ema.europa.eu/en/documents/referral/questions-answers-suspension-marketing-authorisations-oral-meprobamate-containing-medicines_es.pdf.
  • Garcia, A., Fariñas, A.T. & Gálvez, A.M. (2002). Use of meprobamate in the treatment of high blood pressure. Economic consequences. Rev Cubana Farm v.36 n.3 Ciudad de la Habana.
  • Stolerman, I.P. (2010). History of Psychopharmacology. Encyclopedia of Psychopharmacology. Berlin, Heidelberg: Springer-Verlag Berlin Heidelberg.