3-MeO-PCP

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3-MeO-PCP
3-MeO-PCP structure.svg
Clinical data
ATC code
  • None
Legal status
Legal status
Identifiers
  • 1-[1-(3-methoxyphenyl)cyclohexyl]-piperidine
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Chemical and physical data
Formula C18H27NO
Molar mass 273.420 g·mol−1
3D model (JSmol)
  • COc3cccc(c3)C1(CCCCC1)N2CCCCC2
  • InChI=1S/C18H27NO/c1-20-17-10-8-9-16(15-17)18(11-4-2-5-12-18)19-13-6-3-7-14-19/h8-10,15H,2-7,11-14H2,1H3 Yes check.svgY
  • Key:BQQSZHHKGPOXLN-UHFFFAOYSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

3-Methoxyphencyclidine (3-MeO-PCP) is a dissociative hallucinogen of the arylcyclohexylamine class related to phencyclidine (PCP) which has been sold online as a designer drug. [1] [2] [3] It has been used across Europe and the United States. In some cases, consumption has been known to be fatal. It acts mainly as an NMDA receptor antagonist, though it has also been found to interact with the sigma σ1 receptor and the serotonin transporter. [2] [3] The drug does not possess any opioid activity nor does it act as a dopamine reuptake inhibitor. [1] [2] [3]

Contents

Pharmacology

3-MeO-PCP has a Ki of 20 nM for the dizocilpine (MK-801) site of the NMDA receptor, 216 nM for the serotonin transporter (SERT), and 42 nM for the sigma σ1 receptor. [3] [2] It does not bind to the norepinephrine or dopamine transporter nor to the sigma σ2 receptor (Ki >10,000 nM). [2] Based on its structural similarity to 3-hydroxy-PCP (3-HO-PCP), which uniquely among arylcyclohexylamines has high affinity for the μ-opioid receptor in addition to the NMDA receptor, it was initially expected that 3-MeO-PCP would have opioid activity. [1] [4] However, radioligand binding assays with human proteins have shown that, contrary to common belief, the drug also does not interact with the μ-, δ-, or κ- opioid receptors at concentrations of up to 10,000 nM. [2] As such, the notion that 3-MeO-PCP has opioid activity has been described as a myth. [1]

3-MeO-PCP binds to the NMDA receptor with higher affinity than PCP and has the highest affinity of the three isomeric anisyl-substitutions of PCP, followed by 2-MeO-PCP and 4-MeO-PCP. [2] [3]

As of 2018, controlled clinical studies have not been performed in humans but the elimination half-life is estimated to be between 10 and 11 hours. [5]

Chemistry

3-MeO-PCP hydrochloride is a white crystalline solid with a melting point of 204–205 °C. [6]

History

3-MeO-PCP was first synthesized in 1979 to investigate the structure–activity relationships of phencyclidine (PCP) derivatives. The effects of 3-MeO-PCP in humans were not described until 1999 when a chemist using the pseudonym John Q. Beagle wrote that 3-MeO-PCP was qualitatively similar to PCP with comparable potency. [1] Interest in gray-market dissociates accelerated in 2008, when an online research chemical vendor began offering the less potent 4-MeO-PCP. [1] In 2009, a Swiss chemist described the effects of taking the drug on the Bluelight forums. [1] 3-MeO-PCP first became available as a research chemical in 2011. [1] The drug was first reported to the European Monitoring Centre for Drugs and Drug Addiction by the UK on March 29, 2012. [1]

Society and culture

Recreational use

Based on the number of reported intoxications, 3-MeO-PCP is likely more popular than other similar grey market arylcyclohexylamines. [5] 3-MeO-PCP has been available for purchase online as a research chemical. [7] It has been found in drug samples in the United Kingdom and Italy. It is also known to be used in France, The Netherlands, Sweden, The United States, Spain, and the Czech Republic. [8]

3-MeO-PCP is usually taken orally or nasally, but can also be injected or smoked. [9] Duration and onset of effects varies depending on route of administration. When taken orally, onset takes 30-90 minutes and effects last 4-12 hours. [8] Its effects are described as a dissociative hallucinogen, similar to PCP. Being slightly more potent than PCP, threshold activity is exhibited at 3-5mg, with dissociative effects starting at 5mg. [1] Strong dissociative effects are seen at 10mg-20mg. [1] The effects are generally reported as positive, with more euphoria and mental clarity than similar drugs. [1] Negative effects include hypertension, tachycardia, confusion, and disorientation. [5] In one case of an individual taking a very large oral dose (300-500mg), psychosis and aggressive behaviors, followed by amnesia were observed. [10]

As of 2022, there has been two known deaths that can be attributed to 3-MeO-PCP alone; one in Sweden and one in the UK. There were 14 additional deaths where 3-MeO-PCP was detected in the blood post-mortem. [8]

United Kingdom

On October 18, 2012, the Advisory Council on the Misuse of Drugs in the United Kingdom released a report about methoxetamine, saying that the "harms of methoxetamine are commensurate with Class B of the Misuse of Drugs Act (1971)". [11] The report went on to suggest that all analogues of MXE should also become class B drugs and suggested a catch-all clause covering both existing and unresearched arylcyclohexylamines, including 3-MeO-PCP. [3]

United States

3-MeO-PCP is not a controlled substance in the United States but possession or distribution of 3-MeO-PCP for human use could potentially be prosecuted under the Federal Analogue Act due to its structural and pharmacological similarities to PCP. [12]

Canada

Canada's Controlled Drugs And Substances Act has for years placed all PCP analogues, derivatives, salts and further children thereof under a Schedule 1 prohibition, alongside opioids, cocaine and other top-ranked illegal psychoactives. As such, 3-MeO-PCP is automatically banned, although it is not mentioned by name in the schedule. Only PCP and Ketamine are specifically written in. [13]

Sweden

Sweden's public health agency suggested classifying 3-MeO-PCP as hazardous substance on November 10, 2014. [14]

Czech Republic

3-MeO-PCP is banned in the Czech Republic. [15]

Chile

As per Chile's Ley de drogas, aka Ley 20000, [16] all esters and ethers of PCP are illegal. As 3-MeO-PCP is an ether of PCP, it is thus illegal.

Portugal

3-MeO-PCP is neither a salt nor an isomer of PCP, [17] not making it illegal.

See also

Related Research Articles

<span class="mw-page-title-main">Phencyclidine</span> Dissociative hallucinogenic drug, mostly used recreationally

Phencyclidine or phenylcyclohexyl piperidine (PCP), also known in its use as a street drug as angel dust among other names, is a dissociative anesthetic mainly used recreationally for its significant mind-altering effects. PCP may cause hallucinations, distorted perceptions of sounds, and violent behavior. As a recreational drug, it is typically smoked, but may be taken by mouth, snorted, or injected. It may also be mixed with cannabis or tobacco.

<span class="mw-page-title-main">NMDA receptor antagonist</span> Class of anesthetics

NMDA receptor antagonists are a class of drugs that work to antagonize, or inhibit the action of, the N-Methyl-D-aspartate receptor (NMDAR). They are commonly used as anesthetics for humans and animals; the state of anesthesia they induce is referred to as dissociative anesthesia.

<span class="mw-page-title-main">Eticyclidine</span> Medication

Eticyclidine is a dissociative anesthetic drug with hallucinogenic effects. It is similar in effects to phencyclidine but is slightly more potent. PCE was developed by Parke-Davis in the 1970s and evaluated for anesthetic potential under the code name CI-400, but research into PCE was not continued after the development of ketamine, a similar drug with more favourable properties. Due to its similarity in effects to PCP, PCE was placed into the Schedule 1 list of illegal drugs in the 1970s, although it was only briefly abused in the 1970s and 1980s and is now little known.

<span class="mw-page-title-main">Tenocyclidine</span> Chemical compound

Tenocyclidine (TCP) is a dissociative anesthetic with psychostimulant effects. It was discovered by a team at Parke-Davis in the late 1950s. It is similar in effects to phencyclidine (PCP) but is considerably more potent. TCP has slightly different binding properties to PCP, with more affinity for the NMDA receptors, but less affinity for the sigma receptors. Because of its high affinity for the PCP site of the NMDA receptor complex, the 3H radiolabelled form of TCP is widely used in research into NMDA receptors.

<span class="mw-page-title-main">Etoxadrol</span> Chemical compound

Etoxadrol (CL-1848C) is a dissociative anaesthetic drug that has been found to be an NMDA antagonist and produce similar effects to PCP in animals. Etoxadrol, along with another related drug dexoxadrol, were developed as analgesics for use in humans, but development was discontinued in the late 1970s after patients reported side effects such as nightmares and hallucinations.

<span class="mw-page-title-main">Arylcyclohexylamine</span> Class of chemical compounds

Arylcyclohexylamines, also known as arylcyclohexamines or arylcyclohexanamines, are a chemical class of pharmaceutical, designer, and experimental drugs.

<span class="mw-page-title-main">4-MeO-PCP</span> Chemical compound

4-Methoxyphencyclidine is a dissociative anesthetic drug that has been sold online as a research chemical. The synthesis of 4-MeO-PCP was first reported in 1965 by the Parke-Davis medicinal chemist Victor Maddox. A 1999 review published by a chemist using the pseudonym John Q. Beagle suggested the potency of 4-MeO-PCP in man was reduced relative to PCP, two years later Beagle published a detailed description of the synthesis and qualitative effects of 4-MeO-PCP, which he said possessed 70% the potency of PCP. 4-MeO-PCP was the first arylcyclohexylamine research chemical to be sold online, it was introduced in late 2008 by a company trading under the name CBAY and was followed by several related compounds such as 3-MeO-PCP and methoxetamine. 4-MeO-PCP has lower affinity for the NMDA receptor than PCP, but higher affinity than ketamine, it is orally active in a dosage range similar to ketamine, with some users requiring doses in excess of 100 mg for desired effects. Users have reported substantial differences in active dose, these discrepancies can be partially explained by the presence of unreacted PCC and other impurities in samples sold on the grey market. 4-MeO-PCP has Ki values of 404 nM for the NMDA receptor, 713 nM for the norepinephrine transporter, 844 nM for the serotonin transporter, 296 nM for the σ1 receptor and 143 nM for the σ2 receptor.

<span class="mw-page-title-main">Methoxetamine</span> Dissociative drug

Methoxetamine, abbreviated as MXE, is a dissociative hallucinogen that has been sold as a designer drug. It differs from many dissociatives such as ketamine and phencyclidine (PCP) that were developed as pharmaceutical drugs for use as general anesthetics in that it was designed specifically to increase the antidepressant effects of ketamine.

<i>N</i>-Ethylnorketamine Chemical compound

N-Ethylnorketamine is a designer drug which is presumed to have similar properties to ketamine, a dissociative anesthetic drug with hallucinogenic and sedative effects. It has been sold over the internet since around September 2012, and identified in seized drug samples by analytical laboratories in the UK and other European countries.

<span class="mw-page-title-main">Diphenidine</span> Dissociative anesthetic designer drug

Diphenidine is a dissociative anesthetic that has been sold as a designer drug. The synthesis of diphenidine was first reported in 1924, and employed a Bruylants reaction analogous to the one that would later be used to discover phencyclidine in 1956. Shortly after the 2013 UK ban on arylcyclohexylamines, diphenidine and the related compound methoxphenidine became available on the grey market. Anecdotal reports describe high doses of diphenidine producing "bizarre somatosensory phenomena and transient anterograde amnesia." Diphenidine and related diarylethylamines have been studied in vitro as treatments for neurotoxic injury and are antagonists of the NMDA receptor. In dogs diphenidine exhibits greater antitussive potency than codeine phosphate.

<span class="mw-page-title-main">Methoxphenidine</span> Chemical compound

Methoxphenidine is a dissociative of the diarylethylamine class that has been sold online as a designer drug. Methoxphenidine was first reported in a 1989 patent where it was tested as a treatment for neurotoxic injury. Shortly after the 2013 UK ban on arylcyclohexylamines methoxphenidine and the related compound diphenidine became available on the gray market, where it has been encountered as a powder and in tablet form. Though diphenidine possesses higher affinity for the NMDA receptor, anecdotal reports suggest methoxphenidine has greater oral potency. Of the three isomeric anisyl-substituents methoxphenidine has affinity for the NMDA receptor that is higher than 4-MeO-diphenidine but lower than 3-MeO-diphenidine, a structure–activity relationship shared by the arylcyclohexylamines.

<span class="mw-page-title-main">Ephenidine</span> Dissociative anesthetic designer drug

Ephenidine is a dissociative anesthetic that has been sold online as a designer drug. It is illegal in some countries as a structural isomer of the banned opioid drug lefetamine, but has been sold in countries where it is not yet banned.

<span class="mw-page-title-main">3-MeO-PCE</span> Chemical compound

3-Methoxyeticyclidine (3-MeO-PCE), also known as methoxieticyclidine, is a dissociative anesthetic that is qualitatively similar to PCE and PCP and has been sold online as a designer drug.

<span class="mw-page-title-main">3-MeO-PCMo</span> Chemical compound

3-MeO-PCMo is a dissociative anesthetic drug which is similar in structure to phencyclidine and been sold online as a designer drug. The inhibitory effect of 3-MeO-PCMo on the reduction in the density of the drebrin clusters by NMDAR stimulation with glutamic acid is lower than that of PCP or 3-MeO-PCP, with half maximal inhibitory concentration (IC50) values of 26.67 μM (3-MeO-PCMo), 2.02 μM (PCP) and 1.51 μM (3-MeO-PCP).

<span class="mw-page-title-main">3-HO-PCP</span> Chemical compound

3-Hydroxyphencyclidine (3-HO-PCP) is a dissociative of the arylcyclohexylamine class related to phencyclidine (PCP) that has been sold online as a designer drug.

<span class="mw-page-title-main">2-Fluorodeschloroketamine</span> Chemical compound

2-Fluorodeschloroketamine is a dissociative anesthetic related to ketamine. Its sale and use as a designer drug has been reported in various countries. It is an analogue of ketamine where the chlorine group has been replaced by fluorine. Due to its recent emergence, the pharmacological specifics of the compound are mostly unclear, but effects are reported to be similar to its parent compound, ketamine.

<span class="mw-page-title-main">3-Methyl-PCPy</span> Chemical compound

3-Methyl-PCPy (3-Me-PCPy) is an arylcyclohexylamine derivative with an unusual spectrum of pharmacological effects, acting as both a potent NMDA antagonist and also a triple reuptake inhibitor which inhibits reuptake of all three monoamine neurotransmitters serotonin, dopamine and noradrenaline. It also acts as a high affinity sigma receptor ligand, selective for the σ2 subtype. It produces both stimulant and dissociative effects in animal behavioural studies.

<span class="mw-page-title-main">3-Methyl-PCP</span> Chemical compound

3-Methyl-PCP is a recreational designer drug with dissociative effects. It is an arylcyclohexylamine derivative, related to drugs such as 3'-MeO-PCP and 3'-Me-PCPy. It was first synthesised in the 1960s, but was only identified on the illicit market in Hungary in September 2020, and was made illegal in Hungary in April 2021.

<span class="mw-page-title-main">Fluorexetamine</span> Chemical compound

Fluorexetamine is a recreational designer drug from the arylcyclohexylamine family, with dissociative effects. It has reportedly been sold over the internet since around 2017, though has remained relatively uncommon.

<span class="mw-page-title-main">Methylenedioxyphencyclidine</span> Chemical compound

Methylenedioxyphencyclidine is a recreational designer drug with dissociative effects. It is an arylcyclohexylamine derivative, with similar effects to related drugs such as 3-MeO-PCP and 4-MeO-PCP.

References

  1. 1 2 3 4 5 6 7 8 9 10 11 12 Morris H, Wallach J (2014). "From PCP to MXE: a comprehensive review of the non-medical use of dissociative drugs". Drug Testing and Analysis. 6 (7–8): 614–632. doi:10.1002/dta.1620. PMID   24678061.
  2. 1 2 3 4 5 6 7 Roth BL, Gibbons S, Arunotayanun W, Huang XP, Setola V, Treble R, et al. (2013). "The ketamine analogue methoxetamine and 3- and 4-methoxy analogues of phencyclidine are high affinity and selective ligands for the glutamate NMDA receptor". PLOS ONE. 8 (3): e59334. Bibcode:2013PLoSO...859334R. doi: 10.1371/journal.pone.0059334 . PMC   3602154 . PMID   23527166.
  3. 1 2 3 4 5 6 "(ACMD) Methoxetamine Report (2012)" (PDF). UK Home Office. 2012-10-18. p. 14. Retrieved 2012-10-22.
  4. ↑ Morris H (2011-02-11). "Interview with a ketamine chemist: or to be more precise, an arylcyclohexylamine chemist". Vice Magazine. Retrieved 2012-01-23.
  5. 1 2 3 Wallach J, Brandt SD (2018). Maurer HH, Brandt SD (eds.). "Phencyclidine-Based New Psychoactive Substances". Handbook of Experimental Pharmacology. 252. Cham: Springer International Publishing=: 261–303. doi:10.1007/164_2018_124. ISBN   978-3-030-10561-7. PMID   30105474.
  6. ↑ Wallach J, De Paoli G, Adejare A, Brandt SD (2013). "Preparation and analytical characterization of 1-(1-phenylcyclohexyl)piperidine (PCP) and 1-(1-phenylcyclohexyl)pyrrolidine (PCPy) analogues". Drug Testing and Analysis. 6 (7–8): 633–650. doi:10.1002/dta.1468. PMID   23554350.
  7. ↑ De Paoli G, Brandt SD, Wallach J, Archer RP, Pounder DJ (June 2013). "From the street to the laboratory: analytical profiles of methoxetamine, 3-methoxyeticyclidine and 3-methoxyphencyclidine and their determination in three biological matrices". Journal of Analytical Toxicology. 37 (5): 277–283. doi:10.1093/jat/bkt023. PMID   23552616.
  8. 1 2 3 Copeland CS, Hudson S, Treble R, Hamnett HJ (May 2022). "The First Fatal Intoxication with 3-MeO-PCP in the UK and a Review of the Literature". Journal of Analytical Toxicology. 46 (5): 461–470. doi:10.1093/jat/bkac015. PMID   35246686.
  9. ↑ Expert Committee on Drug Dependence 43rd Meeting (20 October 2020). "Critical Review Report: 3-Methoxyphencyclidine (3-MeO-PCP)" (PDF). World Health Organization.
  10. ↑ Pepe M, Di Nicola M, Cocciolillo F, Chiappini S, Martinotti G, Calcagni ML, et al. (March 2024). "3-Methoxy-Phencyclidine Induced Psychotic Disorder: A Literature Review and an 18F-FDG PET/CT Case Report". Pharmaceuticals. 17 (4): 452. doi: 10.3390/ph17040452 . PMC   11053433 . PMID   38675413.
  11. ↑ "Advisory Council on the Misuse of Drugs (ACMD) Methoxetamine report, 2012". Advisory Council on the Misuse of Drugs. 18 October 2012.
  12. ↑ Food and Drug Administration (August 4, 2020). International Drug Scheduling; Convention on Psychotropic Substances; Single Convention on Narcotic Drugs; Isotonitazene; MDMB-4en-PINACA; CUMYL-PEGACLONE; Flubromazolam; Clonazolam; Diclazepam; 3-MeO-PCP; DIPHENIDINE; 2-MEO-DIPHENIDINE; 5-MEO-DALT; and 3-FLUOROPHENMETRAZINE (3-FPM); Request for Comments (Report). pp. 47217–47220. FDA-2020-N-1680. Retrieved June 15, 2024. If intended for human consumption, 3-MeO-PCP may be treated as a "controlled substance analogue
  13. ↑ "Controlled Drugs And Substances Act". Government of Canada Justice Laws. 18 March 2021. Retrieved 25 April 2021.
  14. ↑ "Cannabinoider föreslås bli klassade som hälsofarlig vara" [Cannabinoids are proposed to be classified as a health hazard]. Folkhalsomyndigheten (The Public Health Agency of Sweden). Retrieved 29 June 2015.
  15. ↑ "Látky, o které byl doplněn seznam č. 4 psychotropních látek (příloha č. 4 k nařízení vlády č. 463/2013 Sb.)" [Substances added to list No. 4 of psychotropic substances (Annex No. 4 to Government Regulation No. 463/2013 Coll.)](PDF) (in Czech). Ministerstvo zdravotnictví. Archived from the original (PDF) on 2016-03-09. Retrieved 2016-02-06.
  16. ↑ "Sustituye La Ley Nº 19.366, Que Sanciona El Trafico Ilicito De Estupefacientes Y Sustancias Sicotropicas" [Replaces Law No. 19,366, Which Punishes Illicit Trafficking in Narcotic Drugs and Psychotropic Substances] (in Spanish). Bibloteca Del Congreso Nacional. 22 October 2015. Retrieved 6 February 2018.
  17. ↑ "Legislação de Combate à Droga, Tabela II-A" [Anti-Drug Legislation, Table II-A]. Procuradoria-Geral Distrital de Lisboa (in Portuguese). Ministério Público.
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