NEP: Difference between revisions

The stimulating effects of NEP are believed to mainly be caused by its activity as a [[norepinephrine]]-[[dopamine]] [[reuptake inhibitor]] (NDRI). The reported entactogenic effects it displays may also be due to its activity as a [[serotonin]] [[reuptake inhibitor]] or [[releasing agent]] in moderate to high doses, although new research has shown very low serotonin reuptake inhibition.<ref name=":0">{{cite journal | vauthors=((Duart-Castells, L.)), ((Nadal-Gratacós, N.)), ((Muralter, M.)), ((Puster, B.)), ((Berzosa, X.)), ((Estrada-Tejedor, R.)), ((Niello, M.)), ((Bhat, S.)), ((Pubill, D.)), ((Camarasa, J.)), ((Sitte, H. H.)), ((Escubedo, E.)), ((López-Arnau, R.)) | journal=Neuropharmacology | title=Role of amino terminal substitutions in the pharmacological, rewarding and psychostimulant profiles of novel synthetic cathinones | volume=186 | pages=108475 | date= March 2021 | url=https://linkinghub.elsevier.com/retrieve/pii/S0028390821000290 | issn=00283908 | doi=10.1016/j.neuropharm.2021.108475}}</ref>NEP  probably acts as unselective [[serotonin]]-[[norepinephrine]]-[[dopamine]] [[reuptake inhibitor]] (SNDRI).

NEP shares a close structural relationship to its parent compound [[pentedrone]], differing by an addition ethyl group on the terminal nitrogen on the carbon chain. This addition reportedly makes it about three times as potent as pentedrone.<ref name=":0" /> NEP is also closely related to [[N-Ethylhexedrone]] (commonly known as ''Hexen''), and has been reported as producing largely-similar effects.  

NEP, or N-Ethyl-(nor)-pentedrone, belongs to the [[Substituted cathinone|cathinone]] chemical class. It features a [[phenethylamine]] core with an alkyl group attached to the alpha carbon and an oxygen group attached to the beta carbon. Cathinones are beta-ketone analogues of [[amphetamine]]s. Cathinones refer to a class of molecules which are principally constituted of a [[phenethylamine]] core with an alkyl group attached to the alpha carbon and an oxygen group attached to the beta carbon. They are also known as the beta-ketone (double-bonded oxygen to the β-carbon) analogs of [[amphetamine]]s. The cathinone backbone can be modified in three different places to create hundreds of possible compounds, which include substituents on the aromatic ring, the alpha carbon, and the amine group.<ref>{{cite journal | vauthors=((Liu, C.)), ((Jia, W.)), ((Li, T.)), ((Hua, Z.)), ((Qian, Z.)) | journal=Drug Testing and Analysis | title=Identification and analytical characterization of nine synthetic cathinone derivatives N -ethylhexedrone, 4-Cl-pentedrone, 4-Cl- α -EAPP, propylone, N -ethylnorpentylone, 6-MeO-bk-MDMA, α -PiHP, 4-Cl- α -PHP, and 4-F- α -PHP: Identification of nine synthetic cathinones | volume=9 | issue=8 | pages=1162–1171 | date= August 2017 | url=https://onlinelibrary.wiley.com/doi/10.1002/dta.2136 | issn=19427603 | doi=10.1002/dta.2136}}</ref>

Due to the lack of research regarding the substance, a lot of the discussion regarding the pharmacology of it is purely based upon its structure and subjective effect similarities to other [[Substituted cathinone|cathinone]]s such as [[mephedrone]] and others. However, a recent study has shown that NEP acts as a potent [[Reuptake inhibitor|serotonin-norepinephrine-dopamine reuptake inhibitor]] (SNDRI) with very poor affinity for [[Serotonin|SERT]].<ref name=":0" /> This allows dopamine, serotonin and norepinephrine to accumulate within the brain, resulting in [[stimulation|stimulating]] and [[physical euphoria|euphoric]] effects. That being said, an interaction with other receptor sites cannot yet be fully ruled out.

*'''[[Effect::Abnormal heartbeat]]'''  

*'''[[Effect::Increased heart rate]]''' - NEP increases heart rate significantly compared to other stimulants, even at low doses.

Abuse of compounds within the stimulant class at high dosages for prolonged periods of time can potentially result in a stimulant psychosis that may present with a variety of symptoms (e.g., [[Paranoia|paranoia]], [[External hallucinations|hallucinations]], or [[Delusions|delusions]]).<ref name="Shoptaw2009">{{cite journal | vauthors=((Shoptaw, S. J.)), ((Kao, U.)), ((Ling, W.)) | veditors=((Cochrane Drugs and Alcohol Group)) | journal=Cochrane Database of Systematic Reviews | title=Treatment for amphetamine psychosis | date=21 January 2009 | url=https://doi.wiley.com/10.1002/14651858.CD003026.pub3 | issn=14651858 | doi=10.1002/14651858.CD003026.pub3}}</ref> A review on treatment for amphetamine, [[dextroamphetamine]], and [[methamphetamine]] abuse-induced psychosis states that about 5–15% of users fail to recover completely.<ref name="Shoptaw2009" /><ref>{{cite book | vauthors=((Hofmann, F. G.)) | date= 1983 | title=A handbook on drug and alcohol abuse: the biomedical aspects | publisher=Oxford University Press | edition=2nd ed | isbn=9780195030563}}</ref> The same review asserts that, based upon at least one trial, [[antipsychotic]] medications effectively resolve the symptoms of acute amphetamine psychosis.<ref name="Shoptaw2009" />

*'''Brazil''': On September 7, 2018, all cathinone analogues are controlled substances considered illegal to possess, use and distribute. This was made possible due to a blanket ban law appended to Portaria SVS/MS nº 344.<ref>New blanket ban on synthetic illegal drugs is approved (Portuguese) | http://portal.anvisa.gov.br/noticias/-/asset_publisher/FXrpx9qY7FbU/content/combate-a-drogas-ilicitas-sinteticas-fica-mais-facil</ref>

*'''France''': As a derivative of cathinone with alkyl substitutions on the nitrogen and R2 position, NEP is scheduled as a "stupéfiant", i.e. a recognized drug of abuse. It is illegal to possess, buy, sell or manufacture.<ref>{{Citation | title=Arrêté du 22 février 1990 fixant la liste des substances classées comme stupéfiants  | url=https://www.legifrance.gouv.fr/loda/id/JORFTEXT000000533085/2020-11-20/}}</ref>

*'''Germany''': NEP is controlled under the NpSG (''New Psychoactive Substances Act'')<ref>{{cite web|url=https://www.gesetze-im-internet.de/npsg/anlage.html|title=Anlage NpSG|publisher=Bundesministerium der Justiz und für Verbraucherschutz|access-date=December 11, 2019|language=de}}</ref> as of November 26, 2016.<ref>{{cite web|url=https://www.bgbl.de/xaver/bgbl/start.xav?startbk=Bundesanzeiger_BGBl&jumpTo=bgbl116s2615.pdf#__bgbl__%2F%2F*%5B%40attr_id%3D%27bgbl116s2615.pdf%27%5D__1576017393518|title=Gesetz zur Bekämpfung der Verbreitung neuer psychoaktiver Stoffe|publisher=Bundesanzeiger Verlag|access-date=December 11, 2019|language=de}}</ref> Production and import with the aim to place it on the market, administration to another person and trading is punishable. Possession is illegal but not penalized.<ref>{{cite web|url=https://www.gesetze-im-internet.de/npsg/__4.html|title=§ 4 NpSG|publisher=Bundesministerium der Justiz und für Verbraucherschutz|access-date=December 11, 2019|language=de}}</ref>

*'''Switzerland''': NEP can be considered a controlled substance as a defined derivative of Cathinone under Verzeichnis E point 1. It is legal when used for scientific or industrial use.<ref>{{cite web|url=https://www.admin.ch/opc/de/classified-compilation/20101220/index.html|title=Verordnung des EDI über die Verzeichnisse der Betäubungsmittel, psychotropen Stoffe, Vorläuferstoffe und Hilfschemikalien|publisher=Bundeskanzlei [Federal Chancellery of Switzerland]|access-date=January 1, 2020|language=de}}</ref>

*'''The Netherlands:''' NEP is currently legal, but it is part of a substance group that may be banned soon as part of a recently passed law on New Psychoactive Substances (NPS). <ref>{{Citation|title= Wijziging van de Opiumwet in verband met het toevoegen van een derde lijst met als doel het tegengaan van de productie van en de handel in nieuwe psychoactieve stoffen en enkele andere wijzigingen (Dutch) | year=2024|url=https://www.tweedekamer.nl/kamerstukken/wetsvoorstellen/detail?id=2022Z14042&dossier=36159}}</ref>

*'''United Kingdom''': NEP is a Class B drug in the United Kingdom as a result of the cathinone catch-all clause.<ref>{{Citation | title=The Misuse of Drugs Act 1971 (Amendment) Order 2010 | url=https://www.legislation.gov.uk/uksi/2010/1207/made}}</ref>

*'''United States''': NEP is not a controlled substance in the United States but possession or distribution for human use could potentially be prosecuted under the Federal Analogue Act due to its structural and pharmacological similarities to [[pentedrone]].<ref>{{Citation | title=21 U.S. Code § 813 - Treatment of controlled substance analogues | url=https://www.law.cornell.edu/uscode/text/21/813}}</ref>

*'''Italy:''' NEP is a controlled substance in Italy. It was inserted in "Table 1 of psychotropic substances"<ref>[https://www.salute.gov.it/portale/medicinaliStupefacenti/dettaglioContenutiMedicinaliStupefacenti.jsp?lingua=italiano&id=3729&area=sostanzeStupefacenti&menu=vuoto&tab=1]</ref> in December 29, 2020.

 

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