α-Pyrrolidinopentiophenone (also known as α-pyrrolidinovalerophenone, α-PVP, O-2387, β-keto-prolintane, prolintanone, or desmethylpyrovalerone) is a synthetic

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 developed in the 1960s that has been 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 ...

. Colloquially, it is sometimes called flakka. α-PVP is chemically related to

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 ...

and is the

ketone In organic chemistry, a ketone is a functional group with the structure R–C(=O)–R', where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group –C(=O)– (which contains a carbon-oxygen double bo ...

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 ...

prolintane Prolintane (Catovit, Katovit, Promotil, Villescon) is a stimulant and norepinephrine-dopamine reuptake inhibitor developed in the 1950s. It is the member of amphetamine and derivatives. It is closely related in chemical structure to other drugs ...

Adverse effects

α-PVP, like other psychostimulants, can cause hyperstimulation, paranoia, and hallucinations. α-PVP has been reported to be the cause, or a significant contributory cause of death in suicides and overdoses caused by combinations of drugs. α-PVP has also been linked to at least one death with pulmonary edema and moderately advanced atherosclerotic coronary disease when it was combined with

pentedrone Pentedrone (also known as α-methylaminovalerophenone) is a stimulant of the cathinone class that has been sold as a designer drug and has been found since 2010 as an ingredient in a number of " bath salt" mixes sold as legal highs. Pharmacolo ...

. According to Craig Crespi in the journal '' Case Reports in Psychiatry'', "symptoms are known to easily escalate into frightening delusions, paranoid psychosis, extreme agitation, and a multitude of other altered mental states." Common adverse effects of α-PVP are in line with other psychostimulants, and include: *

Delusion A delusion is a false fixed belief that is not amenable to change in light of conflicting evidence. As a pathology, it is distinct from a belief based on false or incomplete information, confabulation, dogma, illusion, hallucination, or some o ...

s *

Paranoid Paranoia is an instinct or thought process that is believed to be heavily influenced by anxiety or fear, often to the point of delusion and irrationality. Paranoid thinking typically includes persecutory beliefs, or beliefs of conspiracy concer ...

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 ...

* Agitation * Altered mental state In addition, agitated delirium may occur as an adverse effect of α-PVP, which carries its own set of symptoms, including

anxiety Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...

, agitation, violent outbursts,

confusion In medicine, confusion is the quality or state of being bewildered or unclear. The term "acute mental confusion"

myoclonus Myoclonus is a brief, involuntary, irregular (lacking rhythm) twitching of a muscle or a group of muscles, different from clonus, which is rhythmic or regular. Myoclonus (myo "muscle", clonic "jerk") describes a medical sign and, generally, is ...

and

convulsion A convulsion is a medical condition where the body muscles contract and relax rapidly and repeatedly, resulting in uncontrolled shaking. Because epileptic seizures typically include convulsions, the term ''convulsion'' is sometimes used as a s ...

s, with clinical symptoms including

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 ...

diaphoresis Perspiration, also known as sweating, is the production of fluids secreted by the sweat glands in the skin of mammals. Two types of sweat glands can be found in humans: eccrine glands and apocrine glands. The eccrine sweat glands are distribut ...

mydriasis Mydriasis is the dilation of the pupil, usually having a non-physiological cause, or sometimes a physiological pupillary response. Non-physiological causes of mydriasis include disease, trauma, or the use of certain types of drugs. Normally, as ...

and

hyperthermia Hyperthermia, also known simply as overheating, is a condition in which an individual's body temperature is elevated beyond normal due to failed thermoregulation. The person's body produces or absorbs more heat than it dissipates. When extreme ...

Pharmacology

α-PVP acts as a norepinephrine-dopamine reuptake inhibitor with IC₅₀ values of 14.2 and 12.8 nM, respectively, similar to its methylenedioxy derivative

MDPV Methylenedioxypyrovalerone (MDPV) is a stimulant of the cathinone 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 tra ...

. Similar to other

cathinones 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, alon ...

, α-PVP has been shown to have reinforcing effects in rats.

Chemistry

α-PVP gives no reaction with the

Marquis reagent Marquis reagent is used as a simple spot-test to presumptively identify alkaloids as well as other compounds. It is composed of a mixture of formaldehyde and concentrated sulfuric acid, which is dripped onto the substance being tested. The United St ...

. It gives a grey/black reaction with the

Mecke reagent The Mecke reagent is used as a simple spot-test to presumptively identify alkaloids as well as other compounds. It is composed of a mixture of selenous acid and concentrated sulfuric acid, which is dripped onto the substance being tested. The Unit ...

Detection in body fluids

α-PVP may be quantified in blood, plasma or urine by

liquid chromatography-mass spectrometry A liquid is a nearly incompressible fluid that conforms to the shape of its container but retains a (nearly) constant volume independent of pressure. As such, it is one of the four fundamental states of matter (the others being solid, gas, an ...

to confirm a diagnosis of poisoning in hospitalized patients or to provide evidence in a medicolegal death investigation. Blood or plasma α-PVP concentrations are expected to be in a range of 10–50 μg/L in persons using the drug recreationally, >100 μg/L in intoxicated patients and >300 μg/L in victims of acute overdosage.

Society and culture

Legal status

α-PVP is banned in Estonia, Finland, France, Germany, Hungary, Ireland, Latvia, Lithuania, Poland, Romania, Slovenia, Sweden, United Kingdom, Turkey, Norway, as well as the Czech Republic.

Australia

α-PVP is a Schedule 9 prohibited substance under the Poisons Standard (July 2016).Poisons Standard July 201
Comlaw.gov.au
/ref> A Schedule 9 substance is a substance which may be abused or misused, the manufacture, possession, sale or use of which should be prohibited by law except when required for medical or scientific research, or for analytical, teaching or training purposes with approval of Commonwealth and/or State or Territory Health Authorities. The drug was explicitly made illegal in

New South Wales ) , nickname = , image_map = New South Wales in Australia.svg , map_caption = Location of New South Wales in AustraliaCoordinates: , subdivision_type = Country , subdivision_name = Australia , established_title = Before federation , es ...

after it was illegally marketed with the imprimatur of erroneous legal advice that it was not encompassed by analog provisions of the relevant act. It is encompassed by those provisions, and therefore has been illegal for many years in New South Wales. The legislative action followed the death of two individuals from using it; one jumping off a balcony, another having a heart attack after a state of delirium.

EU

α-PVP was required to be banned by EU member states by 3 July 2017 and appears in Schedule II of the UN

Convention on Psychotropic Substances The Convention on Psychotropic Substances of 1971 is a United Nations treaty designed to control psychoactive drugs such as #Amphetamine-type stimulants, amphetamine-type stimulants, barbiturates, benzodiazepines, and Psychedelic drug, psychede ...

China

As of October 2015, α-PVP is a controlled substance in China.

Italy

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 ...

and all structurally derived analogues (including

analogues) were classified as narcotics in January 2012.

US

α-PVP is a Schedule I drug in

New Mexico ) , population_demonym = New Mexican ( es, Neomexicano, Neomejicano, Nuevo Mexicano) , seat = Santa Fe , LargestCity = Albuquerque , LargestMetro = Tiguex , OfficialLang = None , Languages = English, Spanish ( New Mexican), Navajo, Ker ...

Delaware Delaware ( ) is a state in the Mid-Atlantic region of the United States, bordering Maryland to its south and west; Pennsylvania to its north; and New Jersey and the Atlantic Ocean to its east. The state takes its name from the adjacent Del ...

Florida Florida is a state located in the Southeastern region of the United States. Florida is bordered to the west by the Gulf of Mexico, to the northwest by Alabama, to the north by Georgia, to the east by the Bahamas and Atlantic Ocean, and to ...

Oklahoma Oklahoma (; Choctaw language, Choctaw: ; chr, ᎣᎧᎳᎰᎹ, ''Okalahoma'' ) is a U.S. state, state in the South Central United States, South Central region of the United States, bordered by Texas on the south and west, Kansas on the nor ...

, and

Virginia Virginia, officially the Commonwealth of Virginia, is a state in the Mid-Atlantic and Southeastern regions of the United States, between the Atlantic Coast and the Appalachian Mountains. The geography and climate of the Commonwealth ar ...

. On 28 January 2014, the

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 ...

listed it, along with nine other synthetic

, on the

Schedule 1 Schedule 1 may refer to: * Schedule I Controlled Substances within the US Controlled Substances Act * Schedule I Controlled Drugs and Substances within the Canadian Controlled Drugs and Substances Act * Schedule I Psychotropic Substances within t ...

with a temporary ban, effective February 27, 2014. The temporary ban was then extended.

Economics

α-PVP is sometimes the active ingredient in recreational drugs sold 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 ...

". It may also be distinguished from "bath salts" and sold under a different name: "flakka", a name used in Florida, or "gravel" in other parts of the U.S. It is reportedly available as cheaply as US$5 per dose. A laboratory for one county in Florida reported a steady rise in α-PVP detections in seized drugs from none in January–February 2014 to 84 in September 2014.

Notes

References

{{DEFAULTSORT:Pyrrolidinopentiophenone, alpha- Designer drugs Norepinephrine–dopamine reuptake inhibitors Pyrrolidinophenones Stimulants