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((Short description|Tranquilizer based with herbs Valerian, hops, peppermint & phenobarbital, a barbiturate))
((cs1 config|name-list-style=vanc))
((More citations needed|date=June 2022))
[[File:Корвалол-Фармак.jpg|thumb|Corvalol]]

'''Corvalol''' ('''Корвалол''', '''Corvalolum''', '''Korvalol''') is a [[tranquilizer]] based on the herb [[valerian (herb)|valerian]] (''Valeriana officinalis'') root, as well peppermint oil ''[[Mentha piperita]]'' and hop extract ''[[Humulus lupulus]]'' and the [[barbiturate]] [[phenobarbital]], popular in Eastern Europe and the former [[Soviet Union]] 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,((Which?|date=June 2022)) 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.((cn|date=March 2021))

Corvalol was developed in the USSR in 1960 as an analogue of the German drug Valocordin, and is therefore similar in composition and action.<ref>((Cite web|url=https://rg.ru/2016/05/17/uchenye-soobshchili-tajnu-korvalola.html|title=Народный избранник. Корвалол остается одним из самых популярных препаратов|date=17 May 2016 |publisher=Российская Газета|access-date=18 January 2019))</ref>

== Medical uses ==
Corvalol is labeled by the manufacturer for use in:((medcn|date=January 2015))
* [[neuroses]] with heightened irritability
* [[insomnia]]
* as a part of complex treatment of [[hypertension]]
* non-acute [[Coronary vasospasm|spasm of coronary vessels]]
* [[tachycardia]]
* gastrointestinal cramping (as a spasmolytic agent)

=== Valerian extract ===
[[Valerian (herb)|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]] for insomnia and conditions associated with anxiety; however, there is no good evidence that it is effective for these purposes.<ref name=altrev>((cite journal |vauthors=Leach MJ, Page AT |title=Herbal medicine for insomnia: A systematic review and meta-analysis |journal=Sleep Med Rev |volume=24 |pages=1–12 |year=2015 |pmid=25644982 |doi=10.1016/j.smrv.2014.12.003 |type=Review))</ref><ref>((cite journal |vauthors=Miyasaka LS, Atallah AN, Soares BG |title=Valerian for anxiety disorders |journal=Cochrane Database Syst Rev |issue=4 |pages=CD004515 |year=2006 |pmid=17054208 |doi=10.1002/14651858.CD004515.pub2 |type=Systematic review))</ref> The chemical is 3-methylbutyric acid, also known as [[isovaleric acid]] or isopentanoic acid. It is a simple [[short-chain fatty acid]] also produced by many bacteria like many other short chain fatty acids such as [[butyric acid]] and [[propanoic acid]]. 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]] 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.((medcn|date=January 2015))

== 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 [[hypertension]], [[angina]], or respiratory conditions such as [[asthma]]. 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, [[phenobarbital]] 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.<ref>American Geriatrics Society updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. The American Geriatrics Society 2012 Beers Criteria Update Expert Panel.</ref>

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]] depression, confusion, dizziness, [[ataxia]], and [[somnolence]]. In serious cases overdose may result in breathing depression, [[tachycardia]], [[Heart arrhythmia|arrhythmia]], [[hypotension]] (low blood pressure), cardiovascular collapse, and coma.((medcn|date=January 2015))

== Drug interactions ==
Phenobarbital is a strong [[inducer]] (activator) of several hepatic [[cytochrome P450]] enzymes, including [[CYP1A2]], [[CYP2C9]], [[CYP3A4]] and others.<ref>((cite journal |pmid=11996099 | volume=47 | issue=4 | title=Phenobarbital-induced expression of cytochrome P450 genes | year=2000 | journal=Acta Biochim. Pol. | pages=1093–105 | last1 = Czekaj | first1 = P| doi=10.18388/abp.2000_3962 | doi-access=free ))</ref> 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]], [[rivaroxaban]], [[clozapine]], [[itraconazole]], [[nifedipine]], biologics, and many others.
Corvalol may increase CNS depressant effect of other sedatives and hypnotics.((medcn|date=January 2015))

== Pharmaceutical category ==
Corvalol valerianate component of the preparation is purported to offer mild spasmolytic effects on the [[vasculature]]. Phenobarbital is a [[central nervous system]] depressant.((medcn|date=January 2015))

== Composition ==
[[File:2-Bromoisovaleric acid ethyl ester.svg|thumb|right|Ethyl ester of α-bromoisovaleric acid]]

According to the Farmak product label of Corvalol oral solution, the composition per 1 mL (26 drops) is as follows:<ref>((cite web|title=Corvalol (oral solution) Prescribing Information|url=http://farmak.ua/assets_images/drugs/instruction/ru/136/Інструкція_рос_Корв_крап.pdf|publisher=PAO "Farmak"|access-date=14 December 2015|language=ru))((Dead link|date=December 2019 |bot=InternetArchiveBot |fix-attempted=yes ))</ref>
* Ethyl ester of α-bromo[[3-Methylbutanoic acid|isovaleric acid]] (ethyl 2-bromo-3-methylbutyrate) — 20&nbsp;mg
* [[Phenobarbital]] — 18.26&nbsp;mg
* [[Peppermint oil]] — 1.42&nbsp;mg
Inactive ingredients: stabilizer, [[ethanol]] 96%, purified water.

According to the Farmak product label, the composition of 1 tablet is as follows:<ref>((cite web|title=Corvalol (tablets) Prescribing Information|url=http://farmak.ua/assets_images/drugs/instruction/ru/182/Корвалол_табл_рус.pdf|publisher=PAO "Farmak"|access-date=14 December 2015|language=ru|archive-url=https://web.archive.org/web/20160304093848/http://farmak.ua/assets_images/drugs/instruction/ru/182/%D0%9A%D0%BE%D1%80%D0%B2%D0%B0%D0%BB%D0%BE%D0%BB_%D1%82%D0%B0%D0%B1%D0%BB_%D1%80%D1%83%D1%81.pdf|archive-date=4 March 2016|url-status=dead))</ref>
* Ethyl ester of α-bromoisovaleric acid — 12.42&nbsp;mg
* Phenobarbital — 11.34&nbsp;mg
* Peppermint oil — 0.88&nbsp;mg
Inactive ingredients: [[lactose]] monohydrate, [[magnesium stearate]], β-[[cyclodextrin]], [[acesulfame potassium]].

== 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.<ref>U/S/ Department of Justice. Drug Enforcement Administration. Office of Diversion Control. "Controlled Substances Schedules"  http://www.deadiversion.usdoj.gov/schedules/ ((Webarchive|url=https://web.archive.org/web/20130516164501/http://www.deadiversion.usdoj.gov/schedules/ |date=2013-05-16 ))</ref> It is illegal to import Corvalol into the United States.<ref>[https://web.archive.org/web/20060522212854/http://depts.washington.edu/druginfo/Alerts/Details/corvalolum.html Health Hazard with Unapproved Imported Drug from Russia]</ref>

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]] and as a general-purpose tranquilizer/sedative. Despite the -lol suffix, the drug is not a [[beta-blocker]]. 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]], [[Metamizole|metamizole sodium (branded Analgin)]], [[nitroglycerin]], and [[activated charcoal]].

== Manufacturer ==
The prototype of Corvalol, the original medicine Valokordin, is produced by Krewel Meuselbach GmbH in Germany as a sedative.<ref>((cite web|title=Кревель Мойзельбах ГмбХ - Валокордин®|url=http://krewel-meuselbach.ru/valocordin/|access-date=19 January 2019|language=ru))</ref>

Corvalol was produced by Kyiv Chemical and Pharmaceutical Plant in [[Kyiv]], [[Ukraine]] 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.<ref>((cite web|title=[Russian] State Register of Medicines: Corvalol|url=http://grls.rosminzdrav.ru/GRLS.aspx?RegNumber=&MnnR=&lf=&TradeNmR=корвалол&OwnerName=&MnfOrg=&MnfOrgCountry=&isfs=0&isND=-1&regtype=&order=RegDate&orderType=desc&pageNum=1|access-date=14 December 2015|language=ru))</ref>

== Similar products ==
The manufacturer Farmak produces another similar product, Corvaldin, which is similar in composition to Corvalol, but also contains 0.2&nbsp;mg hops oil per 1mL on tincture.<ref>Фармак. "Корвалдин" http://farmak.ua/ru/drugs/135 ((Webarchive|url=https://web.archive.org/web/20141103000653/http://farmak.ua/ru/drugs/135 |date=2014-11-03 ))</ref>

==References==
((Reflist))

==External links==
*((Commonscatinline))

((Sedatives))
((GABAAR PAMs))

[[Category:Alternative medical treatments]]
[[Category:Combination drugs]]
[[Category:Barbiturates]]
[[Category:Russian drugs]]
[[Category:Drugs in the Soviet Union]]

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