Methylenedioxypyrovalerone

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Summary

Methylenedioxypyrovalerone (MDPV) is a cathinone-class stimulant that functions as a norepinephrine-dopamine reuptake inhibitor (NDRI). It originated in the 1960s through development by a team at Boehringer Ingelheim. Notably, MDPV exhibits considerably stronger activity at the dopamine transporter compared to the norepinephrine transporter, while showing minimal activity at the serotonin transporter. MDPV remained relatively obscure as a stimulant until around 2004 when reports emerged of its availability as a designer drug. In the United States, products containing MDPV were sold with labels indicating “bath salts” and marketed as recreational substances in gas stations, a practice reminiscent of the marketing for products like Spice and K2 as incense. The sale of MDPV as “bath salts” ceased in 2011 following a ban.

Identifiers
IUPAC name
CAS Number687603-66-3 
24622-62-6 (HCl)
PubChem CID20111961
ChemSpider16788110 
UNIIE7LD6JMR0L
CompTox Dashboard (EPA)DTXSID90897461
Chemical and physical data
FormulaC16H21NO3
Molar mass275.343 g/mol (freebase) g·mol−1

Appearance

The hydrochloride salt of MDPV presents as an exceptionally fine crystalline powder that is hygroscopic, tending to clump, reminiscent of powdered sugar. Its color varies from pure white to yellowish-tan, and it carries a subtle odor that intensifies as it changes color. Impurities likely include pyrrolidine or alpha-dibrominated alkylphenones, arising from excess pyrrolidine or incomplete amination during synthesis. These impurities contribute to its discoloration and can emit a fishy (pyrrolidine) or bromine-like odor, particularly upon exposure to air, moisture, or bases.

Pharmacology

MDPV lacks FDA-approved medical applications. It has demonstrated robust reinforcing effects and compulsive self-administration in rats, findings that were provisionally established based on documented cases of misuse and addiction in humans before animal testing was conducted. MDPV is the 3,4-methylenedioxy ring-substituted analog of pyrovalerone, a compound developed in the 1960s that was initially used for chronic fatigue treatment and as an anorectic agent but raised concerns due to issues of abuse and dependence[10]. Other drugs sharing a similar chemical structure include α-pyrrolidinopropiophenone (α-PPP), 4′-methyl-α-pyrrolidinopropiophenone (M-α-PPP), 3′,4′-methylenedioxy-α-pyrrolidinopropiophenone (MDPPP), and 1-phenyl-2-(1-pyrrolidinyl)-1-pentanone (α-PVP).

Effects

MDPV functions as a stimulant and has been reported to induce effects similar to those of cocaine, methylphenidate, and amphetamines. Its primary psychological effects are approximately 3 to 4 hours, followed by aftereffects, such as tachycardia, hypertension, and mild stimulation, lasting 6 to 8 hours. High doses have been known to cause intense, prolonged panic attacks in individuals intolerant to stimulants, and there are anecdotal accounts of psychosis resulting from sleep deprivation and addiction when using higher doses or more frequent intervals. Additionally, it has been repeatedly noted to trigger irresistible cravings for re-administration. Reported modes of intake encompass oral consumption, insufflation, smoking, rectal and intravenous use, with an active range of 3–5 mg and typical doses falling within the 5–20 mg range. In mice, repeated MDPV exposure has been found to induce anxiogenic effects and increase aggressive behavior. Similar observations have been noted in humans. MDPV-treated mice also adapted faster to repeated social isolation, akin to MDMA. A cross-sensitization between MDPV and cocaine has been observed, and both drugs restore drug-seeking behavior concerning each other. Memories associated with MDPV require a longer time to be extinguished. In MDPV-treated mice, a priming dose of cocaine induces notable neuroplasticity, indicating a heightened vulnerability to cocaine abuse.

Long-term Effects

The long-term effects of MDPV on humans have not been extensively studied. However, research has suggested that mice treated with MDPV during adolescence exhibit reinforcing behavior patterns towards cocaine that surpass control groups. These behavioral changes are associated with alterations in factor expression directly linked to addiction, indicating an increased susceptibility to cocaine abuse.

Metabolism

MDPV undergoes phase 1 metabolism in the liver through CYP450 2D6, 2C19, 1A2, and COMT. This process transforms it into methyl catechol and pyrrolidine, which are further glucuronate, enabling excretion via the kidneys. Only a small fraction of metabolites is excreted in the stools. Notably, free pyrrolidine is not detectable in the urine.

Detection in Biological Specimens

MDPV can be quantified in blood, plasma, or urine through gas chromatography-mass or liquid chromatography-mass spectrometry. This is used to confirm a diagnosis of poisoning in hospitalized patients or to provide evidence in medicolegal death investigations. Blood or plasma MDPV concentrations typically range from 10–50 μg/L in recreational users, exceeding 50 μg/L in intoxicated patients, and exceeding 300 μg/L in cases of acute overdose.

Legality

In the UK, MDPV is classified as a Class B drug under The Misuse of Drugs Act 1971 (Amendment) Order 2010, rendering it illegal to sell, buy, or possess without a license. MDPV is explicitly listed as a controlled substance in Finland (listed in Appendix IV substance as of June 28, 2010), Denmark, and Sweden. In Western Australia, MDPV was included in Appendix A Schedule 9 of the Poisons Act 1964 as of February 11, 2012, and carries severe penalties for sale or possession. Canada placed MDPV on Schedule I of the Controlled Drugs and Substances Act on September 26, 2012. In the United States, MDPV is a DEA federally scheduled drug temporarily banned by the DEA on October 21, 2011. Several states and regions in the U.S. have specific laws regarding MDPV, including bans in Louisiana, Florida, Kentucky, New Jersey, Tennessee, and Maine.

Documented Fatalities

Numerous documented fatalities and non-fatal intoxications associated with MDPV use have been reported between September 2009 and August 2013 in various European countries.

Overdose Treatment

In cases of MDPV overdose, physicians often administer anxiolytics like benzodiazepines to reduce drug-induced activity in the brain and body. In severe cases, general anesthesia has been utilized due to the ineffectiveness of sedatives. Treatment for severe hypertension, tachycardia, agitation, or seizures in emergency departments typically involves large doses of lorazepam administered intravenously or intramuscularly. Haloperidol is an alternative treatment if lorazepam is ineffective. Beta-blockers are not recommended as they can lead to paradoxical rises in blood pressure. Electroconvulsive therapy (ECT) has been found to improve persistent psychotic symptoms linked to repeated MDPV use.

FAQ

  • What is Methylenedioxypyrovalerone (MDPV)?
  • MDPV is a synthetic stimulant of the cathinone class. Initially developed in the 1960s, it acts as a norepinephrine-dopamine reuptake inhibitor (NDRI).
  • What are the effects of MDPV?
  • MDPV acts as a stimulant and produces effects similar to cocaine, methylphenidate, and amphetamines. These effects typically last for about 3 to 4 hours, with aftereffects like increased heart rate, high blood pressure, and mild stimulation that can persist for 6 to 8 hours. Higher doses can lead to intense panic attacks and potential psychosis.
  • Is MDPV legal?
  • The legal status of MDPV varies by country and region. In some places, it is classified as a controlled substance and is illegal to sell, buy, or possess without a license. It was temporarily banned in the United States in 2011.
  • What are the long-term effects of MDPV use?
  • The long-term effects of MDPV on humans have not been extensively studied. However, research in mice suggests that MDPV use during adolescence may increase vulnerability to cocaine abuse.
  • How is MDPV metabolized in the body?
  • MDPV undergoes liver metabolism via various enzymes, including CYP450 2D6, 2C19, 1A2, and COMT. It is then excreted primarily through the kidneys, with only a small fraction of metabolites in the stools.
  • Is there treatment for MDPV overdose?
  • In cases of MDPV overdose, medical professionals typically use anxiolytics like benzodiazepines to reduce drug-induced activity in the brain and body. Severe cases may require general anesthesia. Treatment for severe hypertension, tachycardia, agitation, or seizures often involves large doses of lorazepam or haloperidol.
  • Are there documented fatalities associated with MDPV use?
  • There have been documented fatalities and non-fatal intoxications related to MDPV use. In some cases, MDPV was found in the systems of individuals who experienced adverse health effects.
  • Can MDPV be detected in biological specimens?
  • MDPV can be quantified in blood, plasma, or urine through various laboratory techniques, such as gas chromatography-mass or liquid chromatography-mass spectrometry. This is done to confirm diagnoses of poisoning or for medicolegal investigations.
  • Is MDPV similar to other drugs?
  • MDPV shares similarities with other substances, including pyrovalerone and related cathinones. It is chemically related to α-pyrrolidinopropiophenone (α-PPP), 4′-methyl-α-pyrrolidinopropiophenone (M-α-PPP), 3′,4′-methylenedioxy-α-pyrrolidinopropiophenone (MDPPP), and 1-phenyl-2-(1-pyrrolidinyl)-1-pentanone (α-PVP).

References

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