Methylenedioxypyrovalerone
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Methylenedioxypyrovalerone (MDPV) is a
stimulant Stimulants (also often referred to as psychostimulants or colloquially as uppers) is an overarching term that covers many drugs including those that increase activity of the central nervous system and the body, drugs that are pleasurable and inv ...
of the
cathinone Cathinone (also known as benzoylethanamine, or β-keto-amphetamine) is a monoamine alkaloid found in the shrub '' Catha edulis'' (khat) and is chemically similar to ephedrine, cathine, methcathinone and other amphetamines. It is probably the m ...
class that acts as a norepinephrine–dopamine reuptake inhibitor (NDRI). It was first developed in the 1960s by a team at Boehringer Ingelheim. Its activity at the dopamine transporter is six times stronger than at the norepinephrine transporter and it is virtually inactive at the
serotonin Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vas ...
transporter. MDPV remained an obscure stimulant until around 2004 when it was reportedly sold as a
designer drug A designer drug is a structural or functional analog of a controlled substance that has been designed to mimic the pharmacological effects of the original drug, while avoiding classification as illegal and/or detection in standard drug tests. Des ...
. In the USA, products containing MDPV and labeled as
bath salts Bath salts are water-soluble, pulverized minerals that are added to water to be used for bathing. They are said to improve cleaning, enhance the enjoyment of bathing, and serve as a vehicle for cosmetic agents. Bath salts have been developed wh ...
were sold as recreational drugs in gas stations, similar to the marketing for
Spice A spice is a seed, fruit, root, bark, or other plant substance primarily used for flavoring or coloring food. Spices are distinguished from herbs, which are the leaves, flowers, or stems of plants used for flavoring or as a garnish. Spices a ...
and K2 as incense, until it was banned in 2011.


Appearance

The hydrochloride salt exists as a very fine crystalline powder; it is
hygroscopic Hygroscopy is the phenomenon of attracting and holding water molecules via either absorption or adsorption from the surrounding environment, which is usually at normal or room temperature. If water molecules become suspended among the substance ...
and thus tends to form clumps, resembling something like powdered sugar. Its color can range from pure white to a yellowish-tan and has a slight odor that strengthens as it colors. Impurities are likely to consist of either pyrrolidine or alpha-dibrominated alkylphenones—respectively, from either excess pyrrolidine or incomplete amination during synthesis. These impurities likely account for its discoloration and fishy (pyrrolidine) or
bromine Bromine is a chemical element with the symbol Br and atomic number 35. It is the third-lightest element in group 17 of the periodic table (halogens) and is a volatile red-brown liquid at room temperature that evaporates readily to form a simila ...
-like odor, which worsens upon exposure to air, moisture, or bases.


Pharmacology

Methylenedioxypyrovalerone has no record of FDA approved medical use. It has been shown to produce robust reinforcing effects and compulsive self-administration in rats, though this had already been provisionally established by a number of documented cases of misuse and addiction in humans before the animal tests were carried out. MDPV is the 3,4-
methylenedioxy Methylenedioxy is the term used in the field of chemistry, particularly in organic chemistry, for a functional group with the structural formula R-O-CH2-O-R' which is connected to the rest of a molecule by two chemical bonds. The methylenedioxy gr ...
ring Ring may refer to: * Ring (jewellery), a round band, usually made of metal, worn as ornamental jewelry * To make a sound with a bell, and the sound made by a bell :(hence) to initiate a telephone connection Arts, entertainment and media Film and ...
- substituted
analog Analog or analogue may refer to: Computing and electronics * Analog signal, in which information is encoded in a continuous variable ** Analog device, an apparatus that operates on analog signals *** Analog electronics, circuits which use analog ...
of the compound
pyrovalerone (Centroton, 4-Methyl-β-keto-prolintane, Thymergix, O-2371) is a psychoactive drug with stimulant effects via acting as a norepinephrine-dopamine reuptake inhibitor (NDRI), and is used for the clinical treatment of chronic fatigue or letharg ...
, developed in the 1960s, which has been used for the treatment of chronic fatigue and as an
anorectic An anorectic or anorexic is a drug which reduces appetite, resulting in lower food consumption, leading to weight loss. By contrast, an appetite stimulant is referred to as orexigenic. The term is (from the Greek ''ἀν-'' (an-) = "without" a ...
, but caused problems of abuse and dependence. Other drugs with a similar chemical structure include α-pyrrolidinopropiophenone (α-PPP),
4'-methyl-α-pyrrolidinopropiophenone 4'-Methyl-α-pyrrolidinopropiophenone (4-MePPP, MPPP or MαPPP) is a stimulant drug and substituted cathinone. It is structurally very similar to Alpha-Pyrrolidinopropiophenone, α-PPP, with only one added methyl group in the para position on t ...
(M-α-PPP), 3',4'-methylenedioxy-α-pyrrolidinopropiophenone (MDPPP) and 1-phenyl-2-(1-pyrrolidinyl)-1-pentanone (α-PVP).


Effects

MDPV acts as a stimulant and has been reported to produce effects similar to those of
cocaine Cocaine (from , from , ultimately from Quechuan languages, Quechua: ''kúka'') is a central nervous system (CNS) stimulant mainly recreational drug use, used recreationally for its euphoria, euphoric effects. It is primarily obtained from t ...
,
methylphenidate Methylphenidate, sold under the brand names Ritalin and Concerta among others, is the most widely prescribed central nervous system (CNS) stimulant medication used to treat attention deficit hyperactivity disorder (ADHD) and, to a lesser exten ...
, and
amphetamine Amphetamine (contracted from alpha- methylphenethylamine) is a strong central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. It is also commonly used ...
s. The primary psychological effects have a duration of roughly 3 to 4 hours, with aftereffects such as
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 (su ...
,
hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), 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. Long-term high bl ...
, and mild stimulation lasting from 6 to 8 hours. High doses have been observed to cause intense, prolonged
panic attack Panic attacks are sudden periods of intense fear and discomfort that may include palpitations, sweating, chest pain or chest discomfort, shortness of breath, trembling, dizziness, numbness, confusion, or a feeling of impending doom or of losing ...
s in stimulant-intolerant users, and there are anecdotal reports of
psychosis Psychosis is a condition of the mind that results in difficulties determining what is real and what is not real. Symptoms may include delusions and hallucinations, among other features. Additional symptoms are incoherent speech and behavior ...
from sleep withdrawal and addiction at higher doses or more frequent dosing intervals. It has also been repeatedly noted to induce irresistible cravings to re-administer. Reported modalities of intake include oral consumption,
insufflation In religious and magical practice, insufflation and exsufflation are ritual acts of blowing, breathing, hissing, or puffing that signify variously expulsion or renunciation of evil or of the devil (the Evil One), or infilling or blessing with go ...
,
smoking Smoking is a practice in which a substance is burned and the resulting smoke is typically breathed in to be tasted and absorbed into the bloodstream. Most commonly, the substance used is the dried leaves of the tobacco plant, which have bee ...
,
rectal The rectum is the final straight portion of the large intestine in humans and some other mammals, and the gut in others. The adult human rectum is about long, and begins at the rectosigmoid junction (the end of the sigmoid colon) at the le ...
and
intravenous Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...
use. It is supposedly active at 3–5 mg, with typical doses ranging between 5–20 mg. When assayed in mice, repeated exposure to MDPV causes not only an anxiogenic effect but also increased aggressive behaviour, a feature that has already been observed in humans. As with MDMA, MDPV also caused a faster adaptation to repeated social isolation. A cross-sensitization between MDPV and cocaine has been evidenced. Furthermore, both psychostimulants, MDPV and cocaine, restore drug-seeking behavior with respect to each other, although relapse into drug-taking is always more pronounced with the conditioning drug. Moreover, memories associated with MDPV require more time to be extinguished. Also, in MDPV-treated mice, a priming-dose of cocaine triggers significant neuroplasticity, implying a high vulnerability to its abuse.


Long-term effects

The long-term effects of MDPV on humans have not been studied, but it has been reported that mice treated with MDPV during adolescence show reinforcing behavior patterns to cocaine that are higher than the control groups. These behavioural changes are related to alterations of factor expression directly related to addiction. All this suggests an increased vulnerability to cocaine abuse.


Metabolism

MDPV undergoes
CYP450 Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various compo ...
2D6, 2C19, 1A2, and
COMT Catechol-''O''-methyltransferase (COMT; ) is one of several enzymes that degrade catecholamines (neurotransmitters such as dopamine, epinephrine, and norepinephrine), catecholestrogens, and various drugs and substances having a catechol structu ...
phase 1 metabolism (liver) into
methylcatechol Methylcatechol may refer to: * Guaiacol (''O''-methylcatechol) * 3-Methylcatechol 3-Methylcatechol is a chemical compound, a methylbenzenediol. Metabolism The enzyme 1,2-dihydroxy-6-methylcyclohexa-3,5-dienecarboxylate dehydrogenase uses 1,2-d ...
and pyrrolidine, which in turn are glucuronated ( uridine 5'-diphospho-glucuronosyl-transferase) allowing it to be excreted by the kidneys, with only a small fraction of the metabolites being excreted into the stools. No free pyrrolidine will be detected in the urine. Molecularly, this is seen as demethylenation of methylenedioxypyrovalerone (
CYP2D6 Cytochrome P450 2D6 (CYP2D6) is an enzyme that in humans is encoded by the ''CYP2D6'' gene. ''CYP2D6'' is primarily expressed in the liver. It is also highly expressed in areas of the central nervous system, including the substantia nigra. CYP2D ...
), followed by
methylation In the chemical sciences, methylation denotes the addition of a methyl group on a substrate, or the substitution of an atom (or group) by a methyl group. Methylation is a form of alkylation, with a methyl group replacing a hydrogen atom. These t ...
of the aromatic ring via
catechol-O-methyl transferase Catechol-''O''-methyltransferase (COMT; ) is one of several enzymes that degrade catecholamines (neurotransmitters such as dopamine, epinephrine, and norepinephrine), catecholestrogens, and various drugs and substances having a catechol structu ...
.
Hydroxylation In chemistry, hydroxylation can refer to: *(i) most commonly, hydroxylation describes a chemical process that introduces a hydroxyl group () into an organic compound. *(ii) the ''degree of hydroxylation'' refers to the number of OH groups in a ...
of both the aromatic ring and side chain then takes place, followed by an oxidation of the pyrrolidine ring to the corresponding
lactam A lactam is a cyclic amide, formally derived from an amino alkanoic acid. The term is a portmanteau of the words ''lactone'' + ''amide''. Nomenclature Greek prefixes in alphabetical order indicate ring size: * α-Lactam (3-atom rings) * β-Lacta ...
, with subsequent detachment and ring opening to the corresponding
carboxylic acid In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an R-group. The general formula of a carboxylic acid is or , with R referring to the alkyl, alkenyl, aryl, or other group. Carboxylic ...
.


Detection in biological specimens

MDPV may be quantified in blood, plasma or urine by gas chromatography-mass spectrometry or liquid chromatography-mass spectrometry to confirm a diagnosis of poisoning in hospitalized patients or to provide evidence in a medicolegal death investigation. Blood or plasma MDPV concentrations are expected to be in a range of 10–50 μg/L in persons using the drug recreationally, >50 μg/L in intoxicated patients, and >300 μg/L in victims of acute overdose.


Legality

In the UK, following the
ACMD The Advisory Council on the Misuse of Drugs (ACMD) is a British statutory non-departmental public body, advisory non-departmental public body, which was established under the Misuse of Drugs Act 1971. Mandate Its terms of reference, according to ...
's report on
substituted cathinone Substituted cathinones, which include some stimulants and entactogens, are derivatives of cathinone. They feature a phenethylamine core with an alkyl group attached to the alpha carbon, and a ketone group attached to the beta carbon, along ...
derivatives, MDPV is a Class B drug under The Misuse of Drugs Act 1971 (Amendment) Order 2010, making it illegal to sell, buy, or possess without a license. MDPV is specifically listed as a
controlled substance A controlled substance is generally a drug or chemical whose manufacture, possession and use is regulated by a government, such as illicitly used drugs or prescription medications that are designated by law. Some treaties, notably the Single ...
in
Finland Finland ( fi, Suomi ; sv, Finland ), officially the Republic of Finland (; ), is a Nordic country in Northern Europe. It shares land borders with Sweden to the northwest, Norway to the north, and Russia to the east, with the Gulf of B ...
(listed appendix IV substance as of June 28, 2010),
Denmark ) , song = ( en, "King Christian stood by the lofty mast") , song_type = National and royal anthem , image_map = EU-Denmark.svg , map_caption = , subdivision_type = Sovereign state , subdivision_name = Danish Realm, Kingdom of Denmark ...
and
Sweden Sweden, formally the Kingdom of Sweden,The United Nations Group of Experts on Geographical Names states that the country's formal name is the Kingdom of SwedenUNGEGN World Geographical Names, Sweden./ref> is a Nordic country located on ...
. In Sweden a 33-year-old man has been sentenced to six years in prison by an
appellate court A court of appeals, also called a court of appeal, appellate court, appeal court, court of second instance or second instance court, is any court of law that is empowered to hear an appeal of a trial court or other lower tribunal. In much of ...
,
Hovrätt The courts of appeal in Sweden and in Finland'','' also known as Hovrätt ( fi, 'Hovioikeus', Swedish: Hovrätt) (literally "Royal Court") deal with appeals against decisions of the district courts. They also are responsible for supervi ...
, for possession of 250 grams of MDPV that had been acquired prior to criminalization.


Australia

In Western Australia, MDPV has been banned under the Poisons Act 1964, having been included in Appendix A Schedule 9 of the Poisons Act 1964 as from February 11, 2012. The
Director of Public Prosecutions The Director of Public Prosecutions (DPP) is the office or official charged with the prosecution of criminal offences in several criminal jurisdictions around the world. The title is used mainly in jurisdictions that are or have been members o ...
for
Western Australia Western Australia (commonly abbreviated as WA) is a state of Australia occupying the western percent of the land area of Australia excluding external territories. It is bounded by the Indian Ocean to the north and west, the Southern Ocean to th ...
announced that anyone intending to sell or supply MDPV faces a maximum $100,000 fine or 25 years in jail. Users face a $2000 fine or two years' jail. Therefore, anyone caught with MDPV can be charged with possession, selling, supplying or intent to sell or supply.


Canada

Canadian Health Minister Leona Aglukkaq announced on June 5, 2012 that MDPV would be listed on Schedule I of the Controlled Drugs and Substances Act, which was realized on September 26, 2012.


United States

In the United States, MDPV is a
DEA The Drug Enforcement Administration (DEA; ) is a United States federal law enforcement agency under the U.S. Department of Justice tasked with combating drug trafficking and distribution within the U.S. It is the lead agency for domestic en ...
federally scheduled drug. On October 21, 2011, the DEA issued a temporary one-year ban on MDPV, classifying it as a schedule I substance. Schedule I status is reserved for substances with a high potential for abuse, no currently accepted use for treatment in the United States and a lack of accepted safety standards for use under medical supervision. Before the federal ban was announced, MDPV was already banned in Louisiana and Florida. On March 24, 2011, Kentucky passed bill HB 121, which makes MDPV, as well as three other cathinones, controlled substances in the state. It also makes it a Class A misdemeanor to sell the drug, and a Class B misdemeanor to possess it. MDPV is banned in
New Jersey New Jersey is a state in the Mid-Atlantic and Northeastern regions of the United States. It is bordered on the north and east by the state of New York; on the east, southeast, and south by the Atlantic Ocean; on the west by the Delaware ...
under Pamela's Law. The law is named after Pamela Schmidt, a
Rutgers University Rutgers University (; RU), officially Rutgers, The State University of New Jersey, is a Public university, public land-grant research university consisting of four campuses in New Jersey. Chartered in 1766, Rutgers was originally called Queen's ...
student who was murdered in March 2011 by an alleged user of MDPV. A toxicology report later found no "bath salts" in his system. On May 5, 2011,
Tennessee Tennessee ( , ), officially the State of Tennessee, is a landlocked state in the Southeastern region of the United States. Tennessee is the 36th-largest by area and the 15th-most populous of the 50 states. It is bordered by Kentucky to th ...
Governor
Bill Haslam William Edward Haslam (; born August 23, 1958) is an American billionaire businessman and politician who served as the 49th governor of Tennessee from 2011 to 2019. A member of the Republican Party, Haslam previously served as the 67th mayor of ...
signed a law making it a crime "to knowingly produce, manufacture, distribute, sell, offer for sale or possess with intent to produce, manufacture, distribute, sell, or offer for sale" any product containing MDPV. On July 6, 2011, the governor of
Maine Maine () is a state in the New England and Northeastern regions of the United States. It borders New Hampshire to the west, the Gulf of Maine to the southeast, and the Canadian provinces of New Brunswick and Quebec to the northeast and north ...
signed a bill establishing fines for possession and penalties for trafficking of MDPV. On October 17, 2011, an
Ohio Ohio () is a state in the Midwestern region of the United States. Of the fifty U.S. states, it is the 34th-largest by area, and with a population of nearly 11.8 million, is the seventh-most populous and tenth-most densely populated. The sta ...
law banning synthetic drugs took effect barring selling and/or possession of "any material, compound, mixture, or preparation that contains any quantity of the following substances having a stimulant effect on the central nervous system, including their salts, isomers, and salts of isomers", listing ephedrine and pyrovalerone. It also specifically includes MDPV, misspelling the full name as "methyenedioxypyrovalerone". Four days after this Ohio law was passed, the DEA's national emergency ban was implemented. On December 8, 2011, under the Synthetic Drug Control Act, the
US House of Representatives The United States House of Representatives, often referred to as the House of Representatives, the U.S. House, or simply the House, is the lower chamber of the United States Congress, with the Senate being the upper chamber. Together they c ...
voted to ban MDPV and a variety of other synthetic drugs that had been legally sold in stores.


Documented fatalities

In April 2011, two weeks after being reported missing, two men in northwestern Pennsylvania were found dead in a remote location on government land. The official cause of death of both men was
hypothermia Hypothermia is defined as a body core temperature below in humans. Symptoms depend on the temperature. In mild hypothermia, there is shivering and mental confusion. In moderate hypothermia, shivering stops and confusion increases. In severe h ...
, but toxicology reports later confirmed that both Troy Johnson, 29, and Terry Sumrow, 28, had ingested MDPV shortly before their deaths. "It wasn't anything to kill them, but enough to get them messed up," the county coroner said. MDPV containers were found in their vehicle along with spoons, hypodermic syringes and marijuana paraphernalia. In April 2011, an
Alton, Illinois Alton ( ) is a city on the Mississippi River in Madison County, Illinois, United States, about north of St. Louis, Missouri. The population was 25,676 at the 2020 census. It is a part of the River Bend area in the Metro-East region of the ...
, woman apparently died from an MDPV overdose. In May 2011, the CDC reported a hospital
emergency department An emergency department (ED), also known as an accident and emergency department (A&E), emergency room (ER), emergency ward (EW) or casualty department, is a medical treatment facility specializing in emergency medicine, the acute care of pati ...
(ED) visit after the use of "bath salts" in Michigan. One person was reported dead on arrival at the ED. Associates of the dead person reported that he had used bath salts. His toxicology results revealed high levels of MDPV in addition to marijuana and prescription drugs. The primary factor contributing to death was cited as MDPV toxicity after autopsy was performed. An incident of hemiplegia has been reported. A total of 107 non-fatal intoxications and 99 analytically confirmed deaths related to MDPV between September 2009 and August 2013 were reported by nine European countries.


Overdose treatment

Physicians often treat MDPV overdose cases with
anxiolytic An anxiolytic (; also antipanic or antianxiety agent) is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxi ...
s, such as
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, to lessen the drug-induced activity in the brain and body. In some cases, general anesthesia was used because sedatives were ineffective. Treatment in the emergency department for severe hypertension, tachycardia, agitation, or seizures consists of large doses of
lorazepam Lorazepam, sold under the brand name Ativan among others, is a benzodiazepine medication. It is used to treat anxiety disorders, trouble sleeping, severe agitation, active seizures including status epilepticus, alcohol withdrawal, and c ...
in 2–4 mg increments every 10–15 minutes intravenously or intramuscularly. If this is not effective,
haloperidol Haloperidol, sold under the brand name Haldol among others, is a typical antipsychotic medication. Haloperidol is used in the treatment of schizophrenia, tics in Tourette syndrome, mania in bipolar disorder, delirium, agitation, acute psychosi ...
is an alternative treatment. It is suggested that the use of
beta blockers Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage cardiac arrhythmia, abnormal heart rhythms, and to protect the heart from a second myocardial infarction, heart attack after a first heart ...
to treat hypertension in these patients can cause an unopposed peripheral alpha-adrenergic effect with a dangerous paradoxical rise in blood pressure.
Electroconvulsive therapy Electroconvulsive therapy (ECT) is a psychiatry, psychiatric treatment where a generalized seizure (without muscular convulsions) is electrically induced to manage refractory mental disorders.Rudorfer, MV, Henry, ME, Sackeim, HA (2003)"Electroco ...
(ECT) has been shown to improve persistent psychotic symptoms associated with repeated MDPV use.


See also

* MDPBP *
MDPHP MDPHP (3',4'-Methylenedioxy-α-pyrrolidinohexiophenone) is a stimulant of the cathinone class originally developed in the 1960s, which has been reported as a novel designer drug. In the UK its slang name is ''monkey dust''. It is closely related ...
* MDPPP


References


External links

*
Erowid MDPV Vault
{{Monoamine reuptake inhibitors Benzodioxoles Cathinones Norepinephrine–dopamine reuptake inhibitors Pyrrolidinophenones Euphoriants Stimulants Designer drugs