Corvalol (Корвалол, Corvalolum, Korvalol) is a

tranquilizer A sedative or tranquilliser is a substance that induces sedation by reducing irritability or excitement. They are central nervous system (CNS) depressants and interact with brain activity, causing its deceleration. Various kinds of sedatives c ...

based on the herb valerian (''Valeriana officinalis'') root, as well as peppermint oil ''

Mentha piperita Peppermint (''Mentha'' × ''piperita'') is a hybrid species of mint, a cross between watermint and spearmint. Indigenous to Europe and the Middle East, the plant is now widely spread and cultivated in many regions of the world.Euro+Med Plantba ...

'', hop extract ''

Humulus lupulus ''Humulus lupulus'', the common hop or hops, is a species of flowering plant in the hemp family, Cannabaceae. It is a perennial, herbaceous climbing plant which sends up new shoots in early spring and dies back to a cold-hardy rhizome in autumn. ...

'', and the

barbiturate Barbiturates are a class of depressant, depressant drugs that are chemically derived from barbituric acid. They are effective when used medication, medically as anxiolytics, hypnotics, and anticonvulsants, but have physical and psychological a ...

phenobarbital Phenobarbital, also known as phenobarbitone or phenobarb, sold under the brand name Luminal among others, is a medication of the barbiturate type. It is recommended by the World Health Organization (WHO) for the treatment of certain types of ...

, popular in Eastern Europe and the former

Soviet Union The Union of Soviet Socialist Republics. (USSR), commonly known as the Soviet Union, was a List of former transcontinental countries#Since 1700, transcontinental country that spanned much of Eurasia from 1922 until Dissolution of the Soviet ...

as a heart medication. It is available as a transparent liquid with a characteristic strong aroma, and as white bi-concave scored tablets. While not available for sale in the Western countries, Corvalol is sometimes brought over from Eastern Europe for self-administration to other countries of residence. Corvalol contains documented amounts of psychoactive chemicals, and may interact with other prescription medications that a person is taking.Morokhina SL, Alyautdin RN, Kaperko DA, Shubnikova EV, Snegireva II, Smirnova YuA (2018). "Adverse Reactions of Drugs Containing Valeriana and Corvalol: Analysis of Spontaneous Reporting". ''Safety and Risk of Pharmacotherapy'' 2018. V. 6, No. 4 https://doi.org/10.30895/2312-7821-2018-6-4-162-173 Corvalol was developed in the USSR in 1960 as an analogue of the German drug Valocordin, and is therefore similar in composition and action.

Medical uses

Corvalol is labeled by the manufacturer for use in: * neuroses with heightened irritability *

insomnia Insomnia, also known as sleeplessness, is a sleep disorder where people have difficulty sleeping. They may have difficulty falling asleep, or staying asleep for as long as desired. Insomnia is typically followed by daytime sleepiness, low ene ...

* as a part of complex treatment of

hypertension Hypertension, also known as high blood pressure, is a Chronic condition, long-term Disease, medical condition in which the blood pressure in the artery, arteries is persistently elevated. High blood pressure usually does not cause symptoms i ...

* non-acute spasm of coronary vessels *

tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal ...

* gastrointestinal cramping (as a spasmolytic agent)

Valerian extract

Valerian extract contains a chemical which is now produced mostly synthetically that is used in the synthesis of one of the components of Corvalol. Valerian has been used in

herbal medicine Herbal medicine (also called herbalism, phytomedicine or phytotherapy) is the study of pharmacognosy and the use of medicinal plants, which are a basis of traditional medicine. Scientific evidence for the effectiveness of many herbal treatments ...

for insomnia and conditions associated with anxiety; however, there is no good evidence that it is effective for these purposes. The chemical is 3-methylbutyric acid, also known as

isovaleric acid Isovaleric acid, also known as 3-methylbutanoic acid or β-methylbutyric acid, is a branched-chain alkyl carboxylic acid with the chemical formula (CH3)2CHCH2CO2H. It is classified as a short-chain fatty acid. Like other low-molecular-weight car ...

or isopentanoic acid.Appazov NO, Seitzhanov SS, Zhunissov AT, Narmanova RA (2017). "Synthesis of cyclohexyl isovalerate by carbonylation of isobutylene with carbon monoxide and cyclohexanol in the presence of Pd (PPh 3) 4‒PPh 3‒TsOH and its antimicrobial activity." ''Russian Journal of Organic Chemistry'', 53, 1596-1597. It is a simple

short-chain fatty acid Short-chain fatty acids (SCFAs) are fatty acids of two to six carbon atoms. The SCFAs' lower limit is interpreted differently, either with one, two, three or four carbon atoms. Derived from intestine, intestinal microbe, microbial fermentation of ...

also produced by many bacteria like many other short chain fatty acids such as

butyric acid Butyric acid (; from , meaning "butter"), also known under the systematic name butanoic acid, is a straight-chain alkyl carboxylic acid with the chemical formula . It is an oily, colorless liquid with an unpleasant odor. Isobutyric acid (2-met ...

and

propanoic acid Propionic acid (, from the Greek words πρῶτος : ''prōtos'', meaning "first", and πίων : ''píōn'', meaning "fat"; also known as propanoic acid) is a naturally occurring carboxylic acid with chemical formula . It is a liquid with a p ...

. It is modified by substituting a bromine functional group when used in Corvalol, and thus, studies on Valerian (or noticing a lack of studies on Valerian) are not even worthy of note when researching about the ingredient in Corvalol, as chemical modifications make the comparison inappropriate.

Phenobarbital

Phenobarbital Phenobarbital, also known as phenobarbitone or phenobarb, sold under the brand name Luminal among others, is a medication of the barbiturate type. It is recommended by the World Health Organization (WHO) for the treatment of certain types of ...

is a barbiturate anticonvulsant used in epilepsy and to induce sedation. Currently there is no evidence to support the use of phenobarbital in cardiovascular or bronchospastic disease states.

Safety

Due to lack of scientific evidence supported by randomized clinical trials in humans, Corvalol and its components should be used with caution in patients with serious cardiovascular conditions, such as

angina Angina, also known as angina pectoris, is chest pain or pressure, usually caused by insufficient blood flow to the heart muscle (myocardium). It is most commonly a symptom of coronary artery disease. Angina is typically the result of parti ...

, or respiratory conditions such as

asthma Asthma is a common long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wh ...

. Prescription medications that have been scientifically proved to be effective in these disease states should be preferred due to evidence supporting their clinical use. According to the American Geriatrics Society,

should not be used in the elderly population due to high rate of physical dependence, tolerance to sleep benefits, and the risk of overdose at low dosages. According to the manufacturer, overdose is possible due to accumulation of the ingredients when Corvalol is used frequently and in large doses. Symptoms of overdose include

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...

depression, confusion, dizziness,

ataxia Ataxia (from Greek α- negative prefix+ -τάξις rder= "lack of order") is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in e ...

, and

somnolence Somnolence (alternatively sleepiness or drowsiness) is a state of strong desire for sleep, or sleeping for unusually long periods (compare hypersomnia). It has distinct meanings and causes. It can refer to the usual state preceding falling aslee ...

. In serious cases overdose may result in breathing depression,

arrhythmia Arrhythmias, also known as cardiac arrhythmias, are irregularities in the cardiac cycle, heartbeat, including when it is too fast or too slow. Essentially, this is anything but normal sinus rhythm. A resting heart rate that is too fast – ab ...

hypotension Hypotension, also known as low blood pressure, is a cardiovascular condition characterized by abnormally reduced blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood and is ...

(low blood pressure), cardiovascular collapse, and coma.

Drug interactions

Phenobarbital is a strong

inducer In molecular biology, an inducer is a molecule that regulates gene expression. An inducer functions in two ways; namely: *By disabling repressors. The gene is expressed because an inducer binds to the repressor. The binding of the inducer to the r ...

(activator) of several hepatic

cytochrome P450 Cytochromes P450 (P450s or CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that mostly, but not exclusively, function as monooxygenases. However, they are not omnipresent; for examp ...

enzymes, including

CYP1A2 Cytochrome P450 1A2 (abbreviated CYP1A2), a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the human body. In humans, the CYP1A2 enzyme is encoded by the ''CYP1A2'' gene. Function ...

CYP2C9 Cytochrome P450 family 2 subfamily C member 9 (abbreviated CYP2C9) is an enzyme protein. The enzyme is involved in the metabolism, by oxidation, of both xenobiotics, including drugs, and endogenous compounds, including fatty acids. In humans, t ...

CYP3A4 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine, which in humans is encoded by ''CYP3A4'' gene. It organic redox reaction, oxidizes small foreign organic molecules ( ...

and others. One of the functions of these enzymes is to change the molecular structure of medications and other substances taken in by the human body. Taking phenobarbital-containing products, such as Corvalol, while taking other medications may reduce their effectiveness. Some of the medications that may have decreased effectiveness when used with Corvalol are

apixaban Apixaban, sold under the brand name Eliquis, is an anticoagulant medication used to treat and prevent blood clots and to prevent stroke in people with nonvalvular atrial fibrillation through directly inhibiting factor Xa. It is used as an al ...

rivaroxaban Rivaroxaban, sold under the brand name Xarelto among others, is an anticoagulant medication (blood thinner) used to treat and reduce the risk of blood clots. Specifically it is used to treat deep vein thrombosis and pulmonary emboli and prev ...

clozapine Clozapine, sold under the brand name Clozaril among others, is a psychiatric medication and was the first atypical antipsychotic to be discovered. It is used primarily to treat people with schizophrenia and schizoaffective disorder who have ...

itraconazole Itraconazole, sometimes abbreviated ITZ, is an antifungal medication used to treat a number of fungal infections. This includes aspergillosis, blastomycosis, coccidioidomycosis, histoplasmosis, and paracoccidioidomycosis. It may be given ...

nifedipine Nifedipine ( ), sold under the brand name Procardia among others, is a calcium channel blocker medication used to manage angina, high blood pressure, Raynaud's phenomenon, and premature labor. It is one of the treatments of choice for Prinzme ...

, biologics, and many others. Corvalol may increase CNS depressant effect of other

sedative A sedative or tranquilliser is a substance that induces sedation by reducing irritability or Psychomotor agitation, excitement. They are central nervous system (CNS) Depressant, depressants and interact with brain activity, causing its decelera ...

s and hypnotics.

Pharmaceutical category

The valerianate component of the preparation is purported to offer mild spasmolytic effects on the

vasculature In vertebrates, the circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the body. It includes the cardiovascular system, or vascular system, that consists of the heart an ...

. Phenobarbital is a

depressant.Serruto A, Soresi M, Pollaccia E, Minissale M, Giannitrapani L, Montalto G, Licata A (2017). "A phenobarbital overdose: a case report". ''ITALIAN JOURNAL OF MEDICINE'', 11(Suppl1), 114-114. https://iris.unipa.it/handle/10447/245266 Clinical study showed that phenobarbital (the ingredient of the corvalol) caused stupor, hypotension, hypertonicity and aminotransferases elevation.

Composition

According to the Farmak product label of Corvalol oral solution, the composition per 1 mL (26 drops) is as follows: * Ethyl ester of α-bromo

(ethyl 2-bromo-3-methylbutyrate) — 20 mg *

— 18.26 mg *

Peppermint oil Peppermint extract is an extract of peppermint (''Mentha × piperita'') made from the essential oil of peppermint leaves. Peppermint is a hybrid of water mint and spearmint. The oil has been used for various purposes over centuries. Peppermint ...

— 1.42 mg Inactive ingredients: stabilizer,

ethanol Ethanol (also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound with the chemical formula . It is an Alcohol (chemistry), alcohol, with its formula also written as , or EtOH, where Et is the ps ...

96%, purified water. According to the Farmak product label, the composition of 1 tablet is as follows: * Ethyl ester of α-bromoisovaleric acid — 12.42 mg * Phenobarbital — 11.34 mg * Peppermint oil — 0.88 mg Inactive ingredients:

lactose Lactose is a disaccharide composed of galactose and glucose and has the molecular formula C12H22O11. Lactose makes up around 2–8% of milk (by mass). The name comes from (Genitive case, gen. ), the Latin word for milk, plus the suffix ''-o ...

monohydrate,

magnesium stearate Magnesium stearate is the chemical compound with the formula . It is a soap, consisting of salt containing two equivalents of stearate (the anion of stearic acid) and one magnesium cation (Mg2+). Magnesium stearate is a white, water-insoluble pow ...

, β-

cyclodextrin Cyclodextrins are a family of cyclic oligosaccharides, consisting of a macrocycle, macrocyclic ring of glucose subunits joined by α-1,4 glycosidic bonds. Cyclodextrins are produced from starch by enzyme, enzymatic conversion. They are used in ...

acesulfame potassium Acesulfame potassium (, or ), also known as acesulfame K or Ace K, is a synthetic calorie-free sugar substitute (artificial sweetener) often marketed under the trade names Sunett and Sweet One. In the European Union, it is known under the E n ...

Legal status

Phenobarbital, one of the principal ingredients in Corvalol, is a DEA Schedule IV substance in the United States. Schedule IV substances have a low potential for abuse relative to substances in Schedules I–III. Examples of Schedule IV substances are alprazolam (Xanax), carisoprodol (Soma), clonazepam (Klonopin), diazepam (Valium) and others. It is illegal to import Corvalol into the United States. In some countries of Eastern Europe, Corvalol is believed to be safe enough to use in recommended doses without prescription. It is widely used to treat

elevated blood pressure Hypertension, also known as high blood pressure, is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms itself. It is, however, a major risk ...

and as a general-purpose tranquilizer/sedative. Despite the -lol suffix, the drug is not a

beta-blocker Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage abnormal heart rhythms ( arrhythmia), and to protect the heart from a second heart attack after a first heart attack (secondary prevention) ...

. Corvalol is so common in Eastern Europe that, in 1996, the Ministry of Health of the Russian Federation included it in the list of mandatory items in all Russian passenger vehicle first aid kits, alongside such drugs as

aspirin Aspirin () is the genericized trademark for acetylsalicylic acid (ASA), a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and inflammation, and as an antithrombotic. Specific inflammatory conditions that aspirin is ...

, metamizole sodium (branded Analgin),

nitroglycerin Nitroglycerin (NG) (alternative spelling nitroglycerine), also known as trinitroglycerol (TNG), nitro, glyceryl trinitrate (GTN), or 1,2,3-trinitroxypropane, is a dense, colorless or pale yellow, oily, explosive liquid most commonly produced by ...

, and

activated charcoal "Activated" is a song by English singer Cher Lloyd. It was released on 22 July 2016 through Vixen Records. The song was made available to stream exclusively on ''Rolling Stone'' a day before to release (on 21 July 2016). Background In an inter ...

Manufacturer

The prototype of Corvalol, the original medicine Valokordin, is produced by Krewel Meuselbach GmbH in Germany as a sedative. Corvalol was produced by Kyiv Chemical and Pharmaceutical Plant in

Kyiv Kyiv, also Kiev, is the capital and most populous List of cities in Ukraine, city of Ukraine. Located in the north-central part of the country, it straddles both sides of the Dnieper, Dnieper River. As of 1 January 2022, its population was 2, ...

Ukraine Ukraine is a country in Eastern Europe. It is the List of European countries by area, second-largest country in Europe after Russia, which Russia–Ukraine border, borders it to the east and northeast. Ukraine also borders Belarus to the nor ...

in 1960–1991, and by its successor, the Joint Stock Company " Farmak", from 1991 onward. Farmak currently owns the exclusive trade mark to the drug name in Ukraine and a number of countries of Eastern Europe and the former Soviet Union, but not in Russia, where Corvalol is available from a number of different drug companies.

Similar products

The manufacturer Farmak produces another similar product, Corvaldin, which is similar in composition to Corvalol, but also contains 0.2 mg hops oil per 1mL on tincture.Фармак. "Корвалдин" http://farmak.ua/ru/drugs/135

References

External links

* {{GABAAR PAMs Alternative medical treatments Combination drugs Barbiturates Russian drugs Drugs in the Soviet Union