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25I-NBOMe

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25I-NBOMe
Clinical data
Routes of
administration		Buccal (sublabial), sublingual, insufflated, inhalation, intravenous, intramuscular, rectal
ATC code
  • none
Legal status
Legal status
Identifiers
  • 2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine
CAS Number
PubChem CID
ChemSpider
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC18H22INO3
Molar mass427.28 g/mol g·mol−1
3D model (JSmol)
  • COC1=CC=CC=C1CNCCC2=CC(=C(C=C2OC)I)OC
  • InChI=1S/C18H22INO3/c1-21-16-7-5-4-6-14(16)12-20-9-8-13-10-18(23-3)15(19)11-17(13)22-2/h4-7,10-11,20H,8-9,12H2,1-3H3 checkY
  • Key:ZFUOLNAKPBFDIJ-UHFFFAOYSA-N checkY
 ☒NcheckY (what is this?)  (verify)

25I-NBOMe (2C-I-NBOMe) is a psychedelic drug and derivative of the substituted phenethylamine psychedelic 2C-I. It was discovered in 2003 by chemist Ralf Heim at the Free University of Berlin, who published his findings in his PhD dissertation.[1] The compound was subsequently investigated by a team at Purdue University led by David Nichols.[2] The carbon-11 labelled version of this compound, [11C]Cimbi-5, was synthesized and validated as a radiotracer for positron emission tomography (PET) in Copenhagen.[3][4] Being the first 5-HT2A receptor full agonist PET radioligand, [11C]Cimbi-5 shows promise as a more functional marker of these receptors, which may be involved in mental disorders such as depression and schizophrenia.[citation needed]

Chemistry and Structure

Like other 2C-X-NBOMe molecules, 25I-NBOMe is a derivative of the 2C family of phenethylamines described by Alexander Shulgin in his book PiHKAL.[5][6] Specifically, 25I-NBOMe is the N-benzyl derivative of the phenethylamine molecule 2C-I, formed by adding a 2-methoxybenzyl (MeOB) onto the nitrogen (N) of the phenethylamine backbone. This substitution significantly increases the potency of the molecule.[5]

Synthesis

25I-NBOMe is usually synthesised from 2C-I and 2-methoxybenzaldehyde, in a reductive alkylation. It can be done stepwise by first making the imine and then reducing the formed imine with sodium borohydride, or by direct reaction with sodium triacetoxyborohydride.[1]

Pharmacology

Ki-values[7][8]
Receptor Ki (nM) ±
5-HT2A 0.044
5-HT2C 2
5-HT6 73 12
μ-opioid 82 14
H1 189 35
5-HT2B 231 73
κ-opioid 288 50

25I-NBOMe acts as a highly potent full agonist for the human 5-HT2A receptor,[7][9] with a Ki of 0.044 nM, making it some sixteen times the potency of 2C-I itself, and a radiolabelled form of 25I-NBOMe can be used for mapping the distribution of 5-HT2A receptors in the brain.[8] It is one of the only full agonists of the human 5-HT2A in existence. In vitro tests showed this compound acted as an agonist but animal studies have not been reported. While the N-benzyl derivatives of 2C-I were significantly increased in potency compared to 2C-I, the N-benzyl derivatives of DOI were inactive.[10]

Ki values of the following targets were greater than 500 nM: 5-HT1A, D3, H2, 5-HT1D, α1A adrenergic, δ opioid, serotonin uptake transporter, 5-HT5A, 5-HT1B, D2, 5-HT7, D1, 5-HT3, 5-HT1E, D5, muscarinic M1-M5, H3, and the dopamine uptake transporter.[8]

A forensic standard of 25I-NBOMe is available, and the compound has been posted on the Forendex website of potential drugs of abuse.[11]

Recreational use

25I-NBOMe had no history of recreational use prior to being sold online as a designer drug in 2010; slang names for the drug now include “25I”, “Smiles”, and “N-bomb”. As a recreational drug, 25I-NBOMe is roughly as potent as and similar in effect to LSD; consequently, the drug is sometimes misrepresented on blotter paper as LSD.[12] Case reports of 25I-NBOMe intoxication, with and without analytical confirmation of the drug in the body, are increasing in the medical literature.[6] The chemical has emerged as a recreational drug in Europe and the United States[13] as well as Australia.[5]

25I-NBOMe is inactive orally, and the most common methods of administration are sublingual, buccal, or nasal. The drug is frequently loaded onto paper tabs, which are administered under the tongue or in the buccal space of the mouth.[5] There are also reports of intravenous injection of dissolved 25I-NBOMe and smoking the drug in powdered form.[13][14]

Internet forum reports suggest that the drug debuted in the United States after an amateur American chemist imported from Europe the drug 2C-I, which was unscheduled in the US at the time, before converting it into its more potent NBOMe form and transferring it to blotter paper.[5] The drug came to media attention in early 2012 after a cluster of seven non-fatal overdoses was reported in and around Richmond, Virginia.[15][16][17]

25I-NBOMe is frequently sold online through vendors on Silk Road or websites specializing in the sale of designer drugs. Online venders frequently ship wholesale orders from China, a manufacturing hub, for sale in the United States, Europe, and Australia.[18] Due to its potency, the drug is highly profitable, as small quantities of the drug can comprise large numbers of doses; one kilogram of powdered 25I-NBOMe can generate up to 20 million recreational doses.[5] Drug dealers often purchase 25I-NBOMe in bulk online and resell individual doses on the street for considerable profit. In Australia, $2 tabs of 25I-NBOMe can be resold for $20–30 each as LSD.[18] There are, however, methods of differentiating between LSD and adulterants like 25I-NBOMe in the field with and without test kits.[19]

Dosage

25I-NBOMe is potent, being active in sub-milligram doses. A common dose of the hydrochloride salt is 600–1,200 µg. The UK Advisory Council on the Misuse of Drugs states that a common dose is between 50 and 100 µg,[5] although other sources indicate that these figures are incorrect; Erowid tentatively suggests that the threshold dosage for humans is 50–250 µg, with a light dose between 200–600 µg, a common dose at 500–800 µg, and a strong dose at 700–1500 µg.[20] At this level of potency, it is difficult to accurately measure a single dose of the powder form, and attempting to do so may put the user at risk of overdose.[5]

Effects

25I-NBOMe effects usually last 6–10 hours if taken sublingually or buccally.[14] When it is insufflated, effects usually last 4–6 hours.[14] Effects can however last significantly longer depending on dosage; durations longer than 12 hours have been reported.

25I-NBOMe can also be vaporized and inhaled, this may cause significantly quicker effects and shorter duration as is expected from that route of administration. This route of administration is however not recommended, unless when using precise liquid measurement, due to the difficulties of measuring and handling substances active in the microgram range.

Case reports of seven British males who presented to an emergency room following analytically confirmed 25I-NBOMe intoxication suggest the following potential adverse effects: tachycardia (n = 7), hypertension (4), agitation (6), aggression, visual and auditory hallucinations (6), seizures (3), hyperpyrexia (3), clonus (2), elevated white cell count (2), elevated creatine kinase (7), metabolic acidosis (3), and acute kidney injury (1).[13]

Tolerance

Users of 25I-NBOMe have reported that it causes physiological tolerance that may last for around 2–3 weeks. This tolerance is described as diminishing the efficacy of subsequent doses of 25I-NBOMe, as well as interfering with the efficacy of other phenethylamines.[21] This kind of temporary, rapidly-developed tolerance is a typical side effect of a number of other drugs of the phenethylamine class, such as MDMA. Note that the duration given is only empirical, and there are no known studies regarding drug tolerances caused by 25I-NBOMe.

Toxicity and harm potential

Recreational use of 25I-NBOME carries significant risk of both pharmacological and behavioral toxicity.[6][13] 25I-NBOMe is a relatively new substance, and little is known about its pharmacological risks or its interaction with other substances. The LD50 has not yet been determined.[22] It is a highly potent serotonin agonist and, due to its psychedelic effects and ambiguous legal status, a designer drug with reports of recreational use beginning in 2010. Reports of deaths and significant injuries have been attributed to the use of 25I-NBOMe, prompting some governments to control its possession, production, and sale. The harm-reduction website Erowid states that 25I-NBOMe is extremely potent and should not be snorted as this method of administration “appears to have led to several deaths in the past year.”[12] Several non-fatal overdoses requiring prolonged hospitalization have also been reported.[5][6][13]

As of May 2013, 25I-NBOMe has reportedly led to five overdose deaths in the United States.[23] In June 2012, two teens in Grand Forks, North Dakota and East Grand Forks, Minnesota fatally overdosed on a substance that was allegedly 25I-NBOMe, resulting in lengthy sentences for two of the parties involved and a Federal indictment against the Texas based online vendor.[24] A 21-year-old man from Little Rock, Arkansas died in October 2012 after taking a liquid drop of the drug nasally at a music festival. He was reported to have consumed caffeinated alcoholic beverages for “several hours” beforehand. It is unclear what other drugs he may have consumed, as autopsies generally do not test for the presence of research chemicals.[25][26] In January 2013, an 18 year-old in Scottsdale, Arizona, died after consuming 25I-NBOMe sold as LSD; a toxicology screening found no other drugs in the person's system. The drug is the suspected cause of death in another Scottsdale, Arizona, incident in April 2013.[5]

25I-NBOMe has been implicated in multiple deaths in Australia.[5] In March 2012, a man in Australia died from injuries sustained by running into trees and power poles while intoxicated by 25I-NBOMe.[27] A Sydney teenager jumped to his death on June 5, 2013. He reportedly jumped off a balcony thinking he could fly.[28]

Australia

25I-NBOMe was explicitly scheduled in Queensland (Australian) drug law in April 2012, as were some related compounds such as 25B-NBOMe.Although there are no specific laws to do with any forms of NBOMe in Australia at the moment.[citation needed]

Israel

Israel banned 25I-NBOMe in 2013.[29]

Russia

Russia was the first country to pass specific regulations on the NBOME series. All drugs in the NBOMe series, including 25I-NBOMe, became illegal in Russia in October 2011.[29]

Sweden

25I-NBOMe were classified as narcotics with effect from Aug 1, 2013.[30]

United Kingdom

N-benzylated phenethylamines such as 25I-NBOMe were initially unaffected by the legal status of phenethylamine-class drugs.[5] The British government issued a temporary class drug order on a list of emerging recreational drugs, including 25I-NBOMe, on 4 June 2013. The order, which took effect on 10 June 2013 and will last for up to twelve months, prohibits the production, import and sale of “the NBOMe and Benzofury groups of substances”.[31]

United States

25I-NBOMe is unscheduled under United States federal law. However, it could be considered an analog of 2C-I (a Schedule I controlled substance) under the Federal Analogue Act. In this case, sale or possession of 25I-NBOMe with the intent of human consumption would be illegal. The United States Department of Homeland Security is currently attempting to prosecute someone in federal court with 25I-related charges under the analogue act.[29] Virginia,[32] Louisiana,[33] and Georgia have specifically scheduled 25I-NBOMe as a Schedule I controlled substance.

See also

References

  1. ^ a b Ralf Heim PhD. (2010-02-28). "Synthese und Pharmakologie potenter 5-HT2A-Rezeptoragonisten mit N-2-Methoxybenzyl-Partialstruktur. Entwicklung eines neuen Struktur-Wirkungskonzepts" (in German). diss.fu-berlin.de. Retrieved 2013-05-10.
  2. ^ Michael Robert Braden PhD. (2007). "Towards a biophysical understanding of hallucinogen action". Purdue University. Retrieved 2012-08-08.
  3. ^ Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.2967/jnumed.109.074021, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with |doi=10.2967/jnumed.109.074021 instead.
  4. ^ Hansen, M. (2011).Design and Synthesis of Selective Serotonin Receptor Agonists for Positron Emission Tomography Imaging of the Brain. PhD Thesis, University of Copenhagen.
  5. ^ a b c d e f g h i j k l Iversen, Les (May 29, 2013). "Temporary Class Drug Order Report on 5-6APB and NBOMe compounds" (PDF). Advisory Council on the Misuse of Drugs. Gov.Uk. Retrieved 16 June 2013.
  6. ^ a b c d Rose, S. Rutherford (2013). "A case of 25I-NBOMe (25-I) intoxication: a new potent 5-HT2A agonist designer drug". Clinical Toxicology. 51 (3): 174–177. doi:10.3109. Retrieved 17 June 2013. {{cite journal}}: Check |doi= value (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  7. ^ a b Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1007/s00259-010-1686-8, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with |doi=10.1007/s00259-010-1686-8 instead.
  8. ^ a b c Nichols DE, Frescas SP, Chemel BR, Rehder KS, Zhong D, Lewin AH (2008). "High Specific Activity Tritium-Labeled N-(2-methoxybenzyl)-2,5-dimethoxy-4-iodophenethylamine (INBMeO): A High Affinity 5-HT2A Receptor-Selective Agonist Radioligand". Bioorganic & Medicinal Chemistry. 16 (11): 6116–23. doi:10.1016/j.bmc.2008.04.050. PMC 2719953. PMID 18468904. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  9. ^ Silva ME, Heim R, Strasser A, Elz S, Dove S (2011). "Theoretical studies on the interaction of partial agonists with the 5-HT(2A) receptor". Journal of Computer-aided Molecular Design. 25 (1): 51–66. doi:10.1007/s10822-010-9400-2. PMID 21088982. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  10. ^ Braden, MR; Parrish, JC; Naylor, JC; Nichols, DE (2006). "Molecular interaction of serotonin 5-HT2A receptor residues Phe339(6.51) and Phe340(6.52) with superpotent N-benzyl phenethylamine agonists". Molecular Pharmacology. 70 (6): 1956–64. doi:10.1124/mol.106.028720. PMID 17000863.
  11. ^ Southern Association of Forensic Scientists http://forendex.southernforensic.org/index.php/detail/index/1145
  12. ^ a b "25I-NBOMe". Erowid. April 26, 2013. Retrieved 7 May 2013.
  13. ^ a b c d e Hill, Simon L. (June 4, 2013). "Severe clinical toxicity associated with analytically confirmed recreational use of 25I–NBOMe: case series". Clinical Toxicology: 1–6. doi:10.3109. Retrieved 17 June 2013. {{cite journal}}: Check |doi= value (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  14. ^ a b c d 2C-I-NBOMe (25I) Effects, Erowid.org, retrieved 2012-10-07
  15. ^ Geller, Laura (2012-02-17). "Kids overdosing on new drug. Laura Geller, WWBT NBC12, Feb 18, 2012". Nbc12.com. Retrieved 2012-08-08.
  16. ^ Geller, Laura. "Chesterfield mom warns of designer drug overdoses. Laura Geller, WWBT NBC12, March 8, 2012". Nbc12.com. Retrieved 2012-08-08.
  17. ^ Araiza, Vanessa (2012-08-02). "New street drug causing concern among medics. Vanessa Araiza, WBRC, Feb 28, 2012". Wsfa.com. Retrieved 2012-08-08.
  18. ^ a b Ralston, Nick (June 6, 2013). "Drug tab cited in fatal fall". Newcastle Herald. Retrieved 23 June 2013.
  19. ^ "LSD Identification Guide". Bunk Police. 2012. Retrieved 8 November 2012.
  20. ^ 2C-I-NBOMe (25I) Dose, Erowid.org, retrieved 2012-10-07
  21. ^ http://www.disregardeverythingisay.com/post/49302181054/25i-nbome-broken-down-and-described
  22. ^ "Fatalities / Deaths". Erowid. April 26, 2013. Retrieved 7 May 2013.
  23. ^ Hastings, Deborah (May 6, 2013). "New drug N-bomb hits the street, terrifying parents, troubling cops". New York Daily News. Retrieved 7 May 2013.
  24. ^ "Breaking Bad: Digital Drug Sales, Analog Drug Deaths. Craig Malisow, Houston Press, March 13, 2013". houstonpress.com. 2013-03-13. Retrieved 2013-05-17.
  25. ^ "21-year-old dies after one drop of new synthetic drug at Voodoo Fest. Naomi Martin, NOLA, November 1, 2012". NOLA.com. 2012-11-01. Retrieved 2012-11-02.
  26. ^ http://www.erowid.org/chemicals/2ci_nbome/2ci_nbome_death.shtml
  27. ^ Rice, Steven (September 12, 2012). "New hallucinogenic drug 25B-NBOMe and 25I-NBOMe led to South Australian man's bizarre death". Adelaide Now. Retrieved 7 May 2013.
  28. ^ CUNEO, CLEMENTINE. "Henry Kwan jumps to his death in a synthetic psychosis". Daily Telegraph, Sydney, Australia. Retrieved 17 June 2013.
  29. ^ http://www.lakemedelsverket.se/upload/lvfs/konsoliderade/LVFS_2011_10_konsoliderad_tom_2013_1.pdf
  30. ^ 'NBOMe' and 'Benzofury' banned, gov.uk, 2013-06-04, retrieved 2013-06-10
  31. ^ http://www.mygov365.com/legislation/view/id/4f15545049e51b63146f1200/tab/overview/
  32. ^ DHH Announces Ban of Deadly Synthetic Drug. Thursday, November 8, 2012
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