NEP: Difference between revisions

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'''N-Ethyl-nor-pentedrone''' (also known as '''N-Ethylpentedrone''', '''Ethyl-pentedrone''' or more commonly, '''NEP''') is a lesser-known novel [[psychoactive class::stimulant]] substance of the [[chemical class::cathinone]] class that produces [[stimulating]], [[euphoric]], and mildly [[entactogenic]] effects when [[Routes of administration|administered]].

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>

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.

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==Pharmacology==

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|norepinephrine-dopamine reuptake inhibitor]] (~~NDRI~~) with very poor affinity for [[Serotonin|SERT]].<ref name=":0" /> This allows dopamine 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.

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.

==Subjective effects==

{{effects/base

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*'''[[Effect::Dehydration]]''' - Dry mouth and increased sweating can occur after consuming NEP. Low doses of the substance in question cause minimal dehydration.

*'''[[Effect::Vasoconstriction]]''' - NEP has been reported as being slightly vasoconstricting.

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

*'''[[Effect::Increased blood pressure]]'''

*'''[[Effect::Increased heart rate]]'''

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

*'''[[Effect::Increased perspiration]]'''

*'''[[Effect::Appetite suppression]]'''

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*'''[[Effect::Ego inflation]]'''

*'''[[Effect::Disinhibition]]

*'''[[Effect::Increased libido]]'''

*'''[[Effect::Increased music appreciation]]'''

*'''[[Effect::Time distortion]]'''

*'''[[Effect::Thought acceleration]]'''

*'''[[Effect::Motivation enhancement]]'''

*'''[[Effect::Compulsive redosing]]'''

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*'''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>

*'''China''': NEP is a controlled substance.{{citation needed}}

*'''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>

*'''Japan''': NEP is a controlled substance.<ref>{{cite web|url=https://www.mhlw.go.jp/seisakunitsuite/bunya/kenkou_iryou/iyakuhin/yakubuturanyou/dl/meisho.pdf|title=指定薬物一覧|publisher=Ministry of Health, Labour and Welfare|access-date=December 27, 2019|language=ja}}</ref>

*'''Sweden''': NEP is a controlled substance as of November 12, 2019.<ref>{{cite web|url=https://svenskforfattningssamling.se/sites/default/files/sfs/2019-10/SFS2019-612.pdf|title=Svensk författningssamling: Förordningom ändring i förordningen (1999:58) om förbud mot vissa hälsofarliga varor|language=sv|access-date=December 27, 2019|publisher=Thomson Förlag}}</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>

*'''The Netherlands:''' NEP is a controlled substance as of July 1, 2025. <ref>{{Citation|title= Bepaalde groepen designerdrugs (ook wel nieuwe psychoactieve stoffen) zijn sinds 1 juli 2025 verboden. Deze stoffen zijn schadelijk. Gebruikers kunnen er gezondheidsproblemen van krijgen en er zelfs door overlijden. | year=2025|url=https://www.rijksoverheid.nl/onderwerpen/drugs/verbod-op-designerdrugs}}</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>

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[[Category:Cathinone]]

[[Category:Research chemical]]

@@ Line 4: / Line 4: @@
 '''N-Ethyl-nor-pentedrone''' (also known as '''N-Ethylpentedrone''', '''Ethyl-pentedrone''' or more commonly, '''NEP''') is a lesser-known novel [[psychoactive class::stimulant]] substance of the [[chemical class::cathinone]] class that produces [[stimulating]], [[euphoric]], and mildly [[entactogenic]] effects when [[Routes of administration|administered]].
-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>
+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.
@@ Line 16: / Line 16: @@
 ==Pharmacology==
-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|norepinephrine-dopamine reuptake inhibitor]] (NDRI) with very poor affinity for [[Serotonin|SERT]].<ref name=":0" /> This allows dopamine 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.
+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.
 ==Subjective effects==
 {{Preamble/SubjectiveEffects}}
 {{effects/base
@@ Line 29: / Line 30: @@
 *'''[[Effect::Dehydration]]''' - Dry mouth and increased sweating can occur after consuming NEP. Low doses of the substance in question cause minimal dehydration.
 *'''[[Effect::Vasoconstriction]]''' - NEP has been reported as being slightly vasoconstricting.
 *'''[[Effect::Abnormal heartbeat]]'''
 *'''[[Effect::Increased blood pressure]]'''
-*'''[[Effect::Increased heart rate]]'''
+*'''[[Effect::Increased heart rate]]''' - NEP increases heart rate significantly compared to other stimulants, even at low doses.
 *'''[[Effect::Increased perspiration]]'''
 *'''[[Effect::Appetite suppression]]'''
@@ Line 48: / Line 49: @@
 *'''[[Effect::Ego inflation]]'''
 *'''[[Effect::Disinhibition]]
+*'''[[Effect::Increased libido]]'''
 *'''[[Effect::Increased music appreciation]]'''
 *'''[[Effect::Time distortion]]'''
-*'''[[Effect::Thought acceleration]]'''
 *'''[[Effect::Motivation enhancement]]'''
 *'''[[Effect::Compulsive redosing]]'''
@@ Line 109: / Line 110: @@
 *'''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>
 *'''China''': NEP is a controlled substance.{{citation needed}}
+*'''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>
 *'''Japan''': NEP is a controlled substance.<ref>{{cite web|url=https://www.mhlw.go.jp/seisakunitsuite/bunya/kenkou_iryou/iyakuhin/yakubuturanyou/dl/meisho.pdf|title=指定薬物一覧|publisher=Ministry of Health, Labour and Welfare|access-date=December 27, 2019|language=ja}}</ref>
 *'''Sweden''': NEP is a controlled substance as of November 12, 2019.<ref>{{cite web|url=https://svenskforfattningssamling.se/sites/default/files/sfs/2019-10/SFS2019-612.pdf|title=Svensk författningssamling: Förordningom ändring i förordningen (1999:58) om förbud mot vissa hälsofarliga varor|language=sv|access-date=December 27, 2019|publisher=Thomson Förlag}}</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>
+*'''The Netherlands:''' NEP is a controlled substance as of July 1, 2025. <ref>{{Citation|title= Bepaalde groepen designerdrugs (ook wel nieuwe psychoactieve stoffen) zijn sinds 1 juli 2025 verboden. Deze stoffen zijn schadelijk. Gebruikers kunnen er gezondheidsproblemen van krijgen en er zelfs door overlijden. | year=2025|url=https://www.rijksoverheid.nl/onderwerpen/drugs/verbod-op-designerdrugs}}</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>
@@ Line 139: / Line 141: @@
 [[Category:Cathinone]]
 [[Category:Research chemical]]
+{{#set:Featured=true}}