naphyrone

{{Drugbox

| IUPAC_name = (RS)-1-naphthalen-2-yl-2-pyrrolidin-1-ylpentan-1-one

| image = Naphyrone.svg

| width = 200px

| tradename =

| pregnancy_category =

| synonyms = O-2482; Naphthylpyrovalerone

| legal_US = Schedule I

| legal_US_comment = {{Cite web |url=https://www.federalregister.gov/articles/2014/03/07/2014-04997/schedules-of-controlled-substances-temporary-placement-of-10-synthetic-cathinones-into-schedule-i |title=Schedules of Controlled Substances: Temporary Placement of 10 Synthetic Cathinones Into Schedule I |access-date=2015-04-05 |archive-date=2015-04-14 |archive-url=https://web.archive.org/web/20150414011610/https://www.federalregister.gov/articles/2014/03/07/2014-04997/schedules-of-controlled-substances-temporary-placement-of-10-synthetic-cathinones-into-schedule-i |url-status=live }}

| legal_UK = Class B

| legal_DE = Anlage II

| legal_status = Poland: I-P{{cite web | title = Ustawa z dnia 15 kwietnia 2011 r. o zmianie ustawy o przeciwdziałaniu narkomanii ( Dz.U. 2011 nr 105 poz. 614 ) | url = http://isap.sejm.gov.pl/DetailsServlet?id | archive-url = https://web.archive.org/web/20120627171819/http://isap.sejm.gov.pl/DetailsServlet?id | url-status = dead | archive-date = June 27, 2012 | publisher = Internetowy System Aktów Prawnych | access-date = 17 June 2011 }}

| bioavailability =

| metabolism =

| elimination_half-life =

| excretion =

| CAS_number = 850352-53-3

| CAS_supplemental =
850352-11-3 (hydrochloride)

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 96ON64182B

| ATC_prefix = none

| ATC_suffix =

| PubChem = 11243002

| ChemSpiderID = 9418039

| C=19 | H=23 | N=1 | O=1

| smiles = CCCC(C(C1=CC2=C(C=C1)C=CC=C2)=O)N3CCCC3

}}

Naphyrone, also known as O-2482 and naphthylpyrovalerone,{{cite news|url=http://uk.news.yahoo.com/5/20100331/twl-deadly-new-legal-drug-bound-for-brit-3fd0ae9.html |title=Deadly New 'Legal' Drug Bound For Britain - Yahoo! News UK |publisher=Uk.news.yahoo.com |date=2010-03-31 |access-date=2010-04-03 |url-status=dead |archive-url=https://web.archive.org/web/20100405232036/http://uk.news.yahoo.com/5/20100331/twl-deadly-new-legal-drug-bound-for-brit-3fd0ae9.html |archive-date=April 5, 2010 }} is a stimulant drug of the cathinone and naphthylaminopropane families. It was derived from pyrovalerone and acts as a serotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI).{{cite journal | vauthors = Meltzer PC, Butler D, Deschamps JR, Madras BK | title = 1-(4-Methylphenyl)-2-pyrrolidin-1-yl-pentan-1-one (Pyrovalerone) analogues: a promising class of monoamine uptake inhibitors | journal = Journal of Medicinal Chemistry | volume = 49 | issue = 4 | pages = 1420–1432 | date = February 2006 | pmid = 16480278 | pmc = 2602954 | doi = 10.1021/jm050797a }} Naphyrone has been reported as a novel designer drug.{{cite news | vauthors = Travis A |url=https://www.theguardian.com/politics/2010/apr/01/nrg1-legal-high-ban-considered |title=NRG-1 may be next legal high to face ban by ministers | Politics |work=The Guardian |date=2010-04-01 |access-date=2010-04-03 |archive-date=2021-05-31 |archive-url=https://web.archive.org/web/20210531150937/https://www.theguardian.com/politics/2010/apr/01/nrg1-legal-high-ban-considered |url-status=live }} No safety or toxicity data is available on the drug.{{cite news|url=http://www.herald.ie/national-news/new-50c-legal-drug-is-more-evil-than-any-head-shop-high-2122823.html|title=New 50c legal drug 'is more evil' than any head shop high| vauthors = Lavery M |date=2 April 2010|publisher=The Herald|access-date=2 April 2010|archive-date=7 April 2010|archive-url=https://web.archive.org/web/20100407225455/http://www.herald.ie/national-news/new-50c-legal-drug-is-more-evil-than-any-head-shop-high-2122823.html|url-status=live}}

The drug has been marketed under the name “NRG-1,” although only a minority of samples of substances sold under this name have been found to actually contain naphyrone,{{cite journal | vauthors = Brandt SD, Sumnall HR, Measham F, Cole J | title = Second generation mephedrone. The confusing case of NRG-1 | journal = BMJ | volume = 341 | pages = c3564 | date = July 2010 | pmid = 20605894 | doi = 10.1136/bmj.c3564 | s2cid = 20354123 }}{{cite journal | vauthors = Brandt SD, Sumnall HR, Measham F, Cole J | title = Analyses of second-generation 'legal highs' in the UK: initial findings | journal = Drug Testing and Analysis | volume = 2 | issue = 8 | pages = 377–382 | date = August 2010 | pmid = 20687197 | doi = 10.1002/dta.155 | citeseerx = 10.1.1.667.4728 }}{{cite journal | vauthors = Wood DM, Davies S, Cummins A, Button J, Holt DW, Ramsey J, Dargan PI | title = Energy-1 ('NRG-1'): don't believe what the newspapers say about it being legal | journal = Emergency Medicine Journal | volume = 28 | issue = 12 | pages = 1068–1070 | date = December 2011 | pmid = 22101594 | pmc = 3062281 | doi = 10.1136/emj.07.2010.3184rep }} and even samples that proved to contain genuine β-naphyrone were in some cases also found to contain the 1-naphthyl isomer α-naphyrone in varying proportions, further confusing the reported effects profile.{{cite journal | vauthors = Brandt SD, Wootton RC, De Paoli G, Freeman S | title = The naphyrone story: The alpha or beta-naphthyl isomer? | journal = Drug Testing and Analysis | volume = 2 | issue = 10 | pages = 496–502 | date = October 2010 | pmid = 20886463 | doi = 10.1002/dta.185 | citeseerx = 10.1.1.669.1137 }}{{cite journal | vauthors = De Paoli G, Maskell PD, Pounder DJ | title = Naphyrone: analytical profile of the new "legal high" substitute for mephedrone | journal = Journal of Forensic and Legal Medicine | volume = 18 | issue = 2 | pages = 93 | date = February 2011 | pmid = 21315306 | doi = 10.1016/j.jflm.2010.12.001 }}

Use in the United Kingdom

Naphyrone emerged as a new legal high in the United Kingdom only months after the ban of similar drug mephedrone (which was also a cathinone derivative). Until July 2010 the substance was not controlled by the Misuse of Drugs Act 1971 and was therefore not illegal for someone to possess. The Medicines Act prevented naphyrone from being sold for human consumption, and therefore it was sometimes sold as 'pond cleaner' or as another substance not normally consumed by humans.{{cn|date=December 2019}}

A study by researchers at Liverpool John Moores University found that only one out of ten products labelled as "NRG-1" actually contained naphyrone when they were subjected to laboratory analysis. Compounds found in products labelled NRG-1 included MDPV, flephedrone, mephedrone, butylone and caffeine, one product tested was inorganic in composition. In the case of an individual possessing a product labelled NRG-1 that contains MDPV or other illegal substances, they are in possession of a controlled substance.

On 12 July 2010, the Home Office announced that naphyrone had been banned and made a Class B drug,{{cite web |url=http://news.bbc.co.uk/1/hi/uk/10602398.stm |title=NRG-1 'legal high' drug is banned |publisher=BBC News |date=2010-07-12 |access-date=2010-07-17 |archive-date=2021-05-31 |archive-url=https://web.archive.org/web/20210531150934/https://www.bbc.com/news/10602398 |url-status=live }} following a report from the Advisory Council on the Misuse of Drugs.{{cite web|url=http://www.homeoffice.gov.uk/publications/drugs/acmd1/naphyrone-report |title=Advisory Council on the Misuse of Drugs Naphyrone Report (2010) |publisher=Home Office |date=2010-07-07 |access-date=2010-07-17 |url-status=dead |archive-url=https://web.archive.org/web/20100717121420/http://www.homeoffice.gov.uk/publications/drugs/acmd1/naphyrone-report |archive-date=2010-07-17 }}{{cite web|url=http://www.opsi.gov.uk/si/si2010/pdf/uksi_20101799_en.pdf |title=The Misuse of Drugs (Amendment No. 2) (England, Wales and Scotland) Regulations 2010 No. 1799 |publisher=Opsi.gov.uk |access-date=2010-07-18}}{{cite web|url=http://www.opsi.gov.uk/si/si2010/em/uksiem_20101799_en.pdf |title=Explanatory Memorandum To The Misuse of Drugs (Amendment No. 2) (England, Wales and Scotland) Regulations 2010 No. 1799 |publisher=Opsi.gov.uk |access-date=2010-07-18}}

Pharmacology

As a triple reuptake inhibitor, naphyrone has been shown in vitro to affect the reuptake of the neurotransmitters serotonin, dopamine and norepinephrine by interacting with the serotonin transporter (SERT), dopamine transporter (DAT), and norepinephrine transporter (NET).

One study found that the dissociation constant of naphyrone interacting with SERT is 33.1 nM ± 1.1, with DAT is 20.1 nM ± 7.1 and with NET is 136 nM ± 27. The concentration of naphyrone required to inhibit the transporters by 50% is 46.0 nM ± 5.5 for SERT, 40.0 nM ± 13 for DAT and 11.7 nM ± 0.9 for NET. Of a number of pyrovalerone analogues tested, naphyrone was found to be the only serotonin–norepinephrine–dopamine reuptake inhibitor found to be active at n M concentrations.

Some samples of β-naphyrone sold have also been found to contain the alternative isomer α-naphyrone,{{cite journal | vauthors = Brandt SD, Wootton RC, De Paoli G, Freeman S | title = The naphyrone story: The alpha or beta-naphthyl isomer? | journal = Drug Testing and Analysis | volume = 2 | issue = 10 | pages = 496–502 | date = October 2010 | pmid = 20886463 | doi = 10.1002/dta.185 | citeseerx = 10.1.1.669.1137 }} presumably produced accidentally as an impurity in synthesis.{{cite web | vauthors = Kelleher C, Christie R, Lalor K, Fox J, Bowden M, O'Donnell C | date = 2011 |url= http://www.nacd.ie/publications/Head_Report2011_overview.pdf|title=An overview of new psychoactive substances and the outlets supplying them|publisher=National Advisory Committee on Drugs|location=Ireland|archive-url=https://web.archive.org/web/20111125050141/http://www.nacd.ie/publications/Head_Report2011_overview.pdf|archive-date=2011-11-25}}{{failed verification|date=August 2014}} The in vitro data available in the scientific literature was all obtained using pure β-naphyrone, and the pharmacological properties of α-naphyrone are unknown, further complicating the pharmacological profile of this little-studied designer drug.

Image:Alpha-naphyrone.svg{{clear left}}