Methylenedioxypyrovalerone

from Wikipedia, the free encyclopedia
Structural formula
Structural formula of methylenedioxypyrovalerone
1: 1 mixture of ( R ) -form (top) and ( S ) -form (bottom)
General
Surname Methylenedioxypyrovalerone
other names
  • MDPV
  • 3,4-methylenedioxypyrovalerone
  • 1- (Benzo [ d ] [1,3] dioxol-5-yl) -2- (pyrrolidin-1-yl) pentan-1-one
Molecular formula C 16 H 21 NO 3
Brief description

white ( hydrochloride ) or brown, yellow-green or gray (free base), amorphous or crystalline powder

External identifiers / databases
CAS number
  • 687603-66-3 (unspec.)
  • 1388142-27-5 ( R -MDPV)
  • 1388142-28-6 ( S -MDPV)
  • 24622-62-6 (unspec., Hydrochloride)
PubChem 20111961
Wikidata Q417010
Drug information
Drug class

CNS stimulant

properties
Molar mass 275.35 g · mol -1
Physical state

firmly

Melting point

238–239 ° C (decomposition)

solubility

Soluble in methanol , ethanol , dimethylformamide , dimethyl sulfoxide.
Poorly soluble in water.
Hydrochloride:
Soluble in chloroform , methanol and water

safety instructions
GHS labeling of hazardous substances
05 - Corrosive 09 - Dangerous for the environment

danger

H and P phrases H: 318-400
P: ?
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Methylenedioxypyrovalerone ( MDPV ) is a stimulant from the cathinone class and acts as a potent norepinephrine - dopamine reuptake inhibitor with cocaine-like characteristics. MDPV is one of the new psychoactive substances and is known under the scene names Flakka ( USA ), Cloud Nine , Monkey Dust , MTV , Magic , Super Coke and Peevee . The handling of the substance is regulated by law in many countries. MDPV causes oxidative stress .

history

The substance was developed in the 1960s by the pharmaceutical company Boehringer Ingelheim and tested for its effectiveness in the treatment of exhaustion syndrome (see pyrovalerone ). After unwanted side effects such as addictive behavior were shown in preclinical tests , the development was discontinued.

In Japan , the substance in 2006 was found in Saxony delivery pure MDPVs out was in 2007, China confiscated. The drug has found widespread use since 2010, particularly in the US. Products containing MDPV and related new psychoactive substances were sold through public outlets (e.g. smart shops ). These products are assigned to the category with the camouflage name " bath salts ". Was or is being sold via Internet mail order and shop sales. The information on the ingredients on the packaging of such products is insufficient or completely misleading.

The first report in the medical literature of a death from MDPV with no identifiable secondary factors is from 2012. There have been more than 100 deaths associated with MDPV in Europe.

effect

MDPV belongs to the group of active substances called stimulants with the following noticeable effects:

  • Physical: increased heartbeat , increased blood pressure , vasoconstriction , sweating
  • Mentally: strong paranoia , increased vigilance and attention, suppression of tiredness, increased mental arousal, intensification of colors, nausea, restlessness and restlessness as well as suppressed need for food.

The effects last for about three to four hours. The aftereffects are palpitations , high blood pressure and a slight stimulation that lasts for six to eight hours. At higher doses, intense panic attacks have been observed in users who are intolerant to stimulants. In addition, sleep deprivation-related psychoses and addictive behavior with high doses or regular use have been reported. MDPV is also known as an aphrodisiac which, when dosed correctly, comes close to the effects of methamphetamine (known as crystal meth) . When consuming it, there is an urge to re-dose, but this is often limited by the unpleasant side effects that occur with higher doses.

There are case reports of kidney and liver failure as well as rhabdomyolysis .

pharmacology

The bioavailability of methylenedioxypyrovalerone is high. The effects and side effects of this chiral compound are mainly based on the S (+) enantiomer . This acts on the transporters for dopamine and noradrenaline as a reuptake inhibitor with an EC 50 of 2 nM and 10 nM, respectively. In addition, MDPV acts as a dopamine secretion.

metabolism

The main metabolites are produced by splitting and removing the methylene group on the benzodioxole . This creates a compound with a catecholic partial structure, which is partially 3'- O -methylated. Numerous other metabolites were also found. An essential pharmacological in vivo activity could not be determined in them.

toxicology

MDPV causes oxidative stress . This goes hand in hand with the exhaustion of glutathione reserves, mitochondrial dysfunction and the disruption of the intracellular homeostasis of the calcium ion concentration. This leads to cell death through apoptosis . Initiator and effector caspases are activated. The toxic effects are increased by hyperthermia .

Impure MDPV can contain bromide ions . In the synthesis of MDPV, bromine is usually used, and organic intermediate compounds containing bromine are formed. In the event of insufficient cleaning, bromine remains in the end product as a residue. The cumulative poisoning is known as bromism .

Treatment of overdose

For emergency treatment of high blood pressure and tachycardia , dual α / β-adrenoceptor antagonists have been proposed. It is not recommended to give pure alpha blockers alone . Caution is also advised against pure beta blockade. Agitation and convulsions can be treated with benzodiazepines (e.g. lorazepam ). The administration of dopamine antagonists such as haloperidol has been described. Hyperthermia can be countered with cooling.

Legal positions

On July 26, 2012, it was included in Annex II of the Narcotics Act and was thus a marketable, non-prescription narcotic.

In Switzerland , with the entry into force of the revised Narcotics Ordinance by Swissmedic on December 1, 2010, the MDPV was made subject to the Narcotics Act and was therefore illegal from then on. Importation, possession , distribution etc. are punished according to the Narcotics Act.

In the UK , MDPV is classified as a Class B drug . Trade, acquisition and possession are therefore illegal without a license.

Although the substance is legal in Australia , it is increasingly being seized by the authorities .

MDPV is also specifically classified as a narcotic drug in Finland , Denmark and Sweden . In Sweden, a 33-year-old man was sentenced to six years in prison for possession of 250 g of MDPV, which he acquired before handling the substance was criminalized. In the USA, several states have implemented an MDPV ban.

On September 25, 2014, the EU banned MDPV, among other things. The manufacture and sale of the substance has therefore been prohibited since the implementation of resolution 2014/688 / EU in national law.

Web links

Press releases

Individual evidence

  1. ↑ M. Coppola, R. Mondola: 3,4-Methylenedioxypyrovalerone (MDPV): Chemistry, pharmacology and toxicology of a new designer drug of abuse marketed online . In: Toxicology Letters . tape 208 , no. 1 , January 5, 2006, p. 12-15 , doi : 10.1016 / j.toxlet.2011.10.002 .
  2. ↑ a b Joshua C. Yohannan, Joseph S. Bozenko, Jr .: The Characterization of 3,4-Methylenedioxypyrovalerone (MDPV) . In: Microgram Journal . tape 7 , no. 1 , 2010, p. 12–15 ( dea.gov [PDF; 689 kB ] full text).
  3. ↑ a b Product information Methylenedioxy Pyrovalerone from Cayman Chemicals, accessed April 1, 2012.
  4. ↑ Template: CL Inventory / not harmonized There is not yet a harmonized classification for this substance . A label of [No public or meaningful name is available] in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA), accessed on July 10, 2019, is derived from a self-classification by the distributor .
  5. ^ Simmler LD et al.: Pharmacological characterization of designer cathinones in vitro . In: British Journal of Pharmacology . tape 168 , issue 2, 2013, p. 458-470 , doi : 10.1111 / j.1476-5381.2012.02145.x , PMID 22897747 , PMC 3572571 (free full text).
  6. ↑ Baumann MH, Partilla JS, Lehner KR, Thorndike EB, Hoffman AF, Holy M, Rothman RB, Goldberg SR, Lupica CR, Sitte HH, Brandt SD, Tella SR, Cozzi NV, Schindler CW: Powerful cocaine-like actions of 3 , 4-methylenedioxypyrovalerone (MDPV), a principal constituent of psychoactive 'bath salts' products . In: Neuropsychopharmacology . 38, No. 4, 2013, pp. 552-62. doi : 10.1038 / npp.2012.204 . PMID 23072836 . PMC 3572453 (free full text).
  7. ↑ pyrrolidino ketones. US3314970 A
  8. ↑ 1- (3 ', 4'-methylenedioxy-phenyl) -2-pyrrolidino-alkanones- (1). US 3478050 A
  9. ↑ F. Westphal, T. Junge, P. Rösner, F. Sönnichsen, F. Schuster: Mass and NMR spectroscopic characterization of 3,4-methylenedioxypyrovalerone: A designer drug with alpha-pyrrolidinophenone structure . In: Forensic Science International . 190, No. 1–3, 2009, p. 1. doi : 10.1016 / j.forsciint.2009.05.001 . PMID 19500924 .
  10. ↑ Araújo AM, Valente MJ, Carvalho M, Dias da Silva D, Gaspar H, Carvalho F, de Lourdes Bastos M, Guedes de Pinho P: Raising awareness of new psychoactive substances: chemical analysis and in vitro toxicity screening of 'legal high' packages containing synthetic cathinones . In: Arch. Toxicol. . 89, No. 5, 2015, pp. 757-71. doi : 10.1007 / s00204-014-1278-7 . PMID 24903018 .
  11. ↑ Brittany L. Murray, Christine M. Murphy, Michael C. Beuhler: Death Following Recreational Use of Designer Drug “Bath Salts” Containing 3,4-Methylenedioxypyrovalerone (MDPV) . In: Journal of Medical Toxicology . 8, No. 1, 2012, pp. 69-75. doi : 10.1007 / s13181-011-0196-9 .
  12. ^ Edward A. Ross, Gary M. Reisfield, Mary C. Watson, Chris W. Chronister, Bruce A. Goldberger: Psychoactive "Bath Salts" Intoxication with Methylenedioxypyrovalerone . In: The American Journal of Medicine . 125, No. 9, 2012, pp. 854-858. doi : 10.1016 / j.amjmed.2012.02.019 .
  13. ↑ S. Fröhlich, E. Lambe, J. O'Dea: Acute liver failure following recreational use of psychotropic “head shop” compounds . In: Irish Journal of Medical Science . 180, No. 1, 2010, pp. 263-264. doi : 10.1007 / s11845-010-0636-6 .
  14. ↑ Heather A. Borek, Christopher P. Holstege: Hyperthermia and Multiorgan Failure After Abuse of “Bath Salts” Containing 3,4-Methylenedioxypyrovalerone . In: Annals of Emergency Medicine . 60, No. 1, 2012, pp. 103-105. doi : 10.1016 / j.annemergmed.2012.01.005 .
  15. ↑ R. Kolanos, JS Partilla, MH Baumann, BA Hutsell, ML Banks, SS Negus, RA Glennon: Stereoselective Actions of Methylenedioxypyrovalerone (MDPV) To Inhibit Dopamine and Norepinephrine Transporters and Facilitate Intracranial Self-Stimulation in Rats . In: ACS Chemical Neuroscience . 6, No. 5, 2015, pp. 771-777. doi : 10.1021 / acschemneuro.5b00006 .
  16. ↑ Shekar A, Aguilar JI, Galli G, Cozzi NV, Brandt SD, Ruoho AE, Baumann MH, Matthies HJ, Galli A: Atypical dopamine efflux caused by 3,4-methylenedioxypyrovalerone (MDPV) via the human dopamine transporter . In: J. Chem. Neuroanat. . 2017. doi : 10.1016 / y.jchemneu.2017.01.004 . PMID 28163218 .
  17. ↑ Meyer MR, Du P, Schuster F, Maurer HH: Studies on the metabolism of the α-pyrrolidinophenone designer drug methylenedioxy-pyrovalerone (MDPV) in rat and human urine and human liver microsomes using GC-MS and LC-high-resolution MS and its detectability in urine by GC-MS . In: J Mass Spectrom . 45, No. 12, 2010, pp. 1426-42. doi : 10.1002 / jms.1859 . PMID 21053377 .
  18. ↑ Baumann MH, Bukhari MO, Lehner KR, Anizan S, Rice KC, Concheiro M, Huestis MA: Neuropharmacology of 3,4-Methylenedioxypyrovalerone (MDPV), Its Metabolites, and Related Analogs . In: Curr Top Behav Neurosci . 2016. doi : 10.1007 / 7854_2016_53 . PMID 27830575 .
  19. ↑ Negreira N, Erratico C, Kosjek T, van Nuijs AL, Heath E, Neels H, Covaci A: In vitro Phase I and Phase II metabolism of α-pyrrolidinovalerophenone (α-PVP), methylenedioxypyrovalerone (MDPV) and methedrone by human liver microsomes and human liver cytosol . In: Anal Bioanal Chem . 407, No. 19, 2015, pp. 5803-16. doi : 10.1007 / s00216-015-8763-6 . PMID 26014283 .
  20. ↑ Valente MJ, Araújo AM, Silva R, Bastos Mde L, Carvalho F, Guedes de Pinho P, Carvalho M: 3,4-Methylenedioxypyrovalerone (MDPV): in vitro mechanisms of hepatotoxicity under normothermic and hyperthermic conditions . In: Arch. Toxicol. . 90, No. 8, 2016, pp. 1959–73. doi : 10.1007 / s00204-015-1653-z . PMID 26676947 .
  21. ↑ Valente MJ, Bastos ML, Fernandes E, Carvalho F, Guedes de Pinho P, Carvalho M: Neurotoxicity of β-Keto Amphetamines: Deathly Mechanisms Elicited by Methylone and MDPV in Human Dopaminergic SH-SY5Y Cells . In: ACS Chem Neurosci . 2017. doi : 10.1021 / acschemneuro.6b00421 . PMID 28067045 .
  22. ↑ Wood MR, Lalancette RA, Bernal I: Crystallographic investigations of select cathinones: emerging illicit street drugs known as `bath salts' . In: Acta Crystallogr C Struct Chem . 71, No. Pt 1, 2015, pp. 32-8. doi : 10.1107 / S2053229614025637 . PMID 25567572 .
  23. ↑ Schindler CW, Thorndike EB, Suzuki M, Rice KC, Baumann MH: Pharmacological mechanisms underlying the cardiovascular effects of the "bath salt" constituent 3,4-methylenedioxypyrovalerone (MDPV) . In: Br. J. Pharmacol. . 173, No. 24, 2016, pp. 3492-3501. doi : 10.1111 / bph.13640 . PMID 27714779 .
  24. ^ A b "Bath Salts" Health Care Provider Fact Sheet . Michigan Department of Community Health. April 30, 2012.
  25. ↑ Law on the traffic with narcotics (Narcotics Act, BtMG): Annex II (marketable but not prescription drugs)
  26. ↑ Text of the Swissmedic Narcotics Ordinance, which came into force on December 1, 2010, as PDF .
  27. ↑ Text of the Swiss Narcotics Act as PDF. Relevant criminal provisions: Art. 19 and following. .
  28. ↑ Implementing decision of the Council of September 25, 2014 (2014/688 / EU) (PDF) accessed on October 17, 2014.
  29. ↑ EU bans four dangerous designer drugs. In: aerzteblatt.de. September 26, 2014, accessed April 28, 2018 .