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 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>

*'''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.

*'''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.

==See also==

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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 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>
-*'''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.
+*'''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.
 ==See also==
@@ Line 138: / Line 141: @@
 [[Category:Cathinone]]
 [[Category:Research chemical]]
+{{#set:Featured=true}}