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AH-7921

Opioid analgesic


Opioid analgesic

FieldValue
Verifiedfieldschanged
Watchedfieldschanged
verifiedrevid477235538
IUPAC_name3,4-dichloro-N-{[1-(dimethylamino)cyclohexyl]methyl}benzamide
imageAH-7921 structure.svg
image_classskin-invert-image
width220
image2AH-7921 3D BS.png
image_class2bg-transparent
width2220
pregnancy_AU
pregnancy_US
legal_AUS9
legal_BRF1
legal_CASchedule I
legal_UKClass A
legal_USSchedule I
legal_DEAnlage II
routes_of_administrationRecreational: insufflation, sublingual, intravenous, oral, rectal
CAS_number_Ref
CAS_number55154-30-8
ATC_prefixnone
PubChem187760
KEGGC22729
DrugBank_Ref
ChemSpiderID_Ref
ChemSpiderID163208
synonymsAH-7921
UNII_Ref
UNII10BR7A0SO0
C16H=22Cl=2N=2O=1
smilesClC1=CC=C(C(NCC2(CCCCC2)N(C)C)=O)C=C1Cl
StdInChI_Ref
StdInChI1S/C16H22Cl2N2O/c1-20(2)16(8-4-3-5-9-16)11-19-15(21)12-6-7-13(17)14(18)10-12/h6-7,10H,3-5,8-9,11H2,1-2H3,(H,19,21)
StdInChIKey_Ref
StdInChIKeyJMZROFPPEXCTST-UHFFFAOYSA-N

In General Unscheduled, Illegal in Sweden, Czech Republic, China, Brazil and Israel.

| elimination_half-life =

AH-7921 (Doxylam) is an opioid analgesic drug selective for the μ-opioid receptor, having around 90% the potency of morphine when administered orally. It was discovered in the 1970s by a team at Allen and Hanburys located in the United Kingdom. The drug is considered a new psychoactive substance (NPS), a designation of compounds designed to mimic the effects controlled substances. It has also been sold on the internet since 2012 as a "research chemical". When sold online it may be called the alternative name doxylam, not to be confused with doxylamine. AH-7921 has never progressed to clinical trials. The DEA is not aware of any medical usage in the United States, and has not insisted the Health and Human Services department (HHS) to conduct any medical research of the substance's uses.

Side effects and withdrawal

With doses that usually range from 10 to 150 mg, users are likely to experience effects similar to heroin, morphine, and fentanyl such as euphoria and respiratory depression. When an overdose occurs users often experience tachycardia, hypertension, and seizures. Mice, dogs, and monkeys, have been used in tests which showed the drug was almost equivalently potent to morphine, and had a very steep dose response curve. Rats given 20 mg doses three times a day for five days experienced withdrawal symptoms similar to other opioids. Reports have shown users to experience depression and insomnia when withdrawing from this drug.

Chemistry

AH-7921 is commonly found as an off-white solid with a melting point between 215–216º Celsius. It is one single covalently bonded unit with 4 rotatable bonds. It also has two hydrogen bond acceptors, and one hydrogen bond donor.

Use

Although AH-7921 was extensively studied in vitro and in animals, though not in humans, by the developing company, it was never sold commercially for medical use. In 2013, AH-7921 was discovered to have been used as an active ingredient in "synthetic cannabis" products in Japan. In October 2015, two horses (Bossmon and Literata) trained by owner-trainer Roy Sedlacek tested positive for AH-7921 at Belmont Park racetrack. Norway and Iceland use this substance as an analytical reference standard in which it can be ordered online from chemical suppliers; however, labels are required to state that it is not for human consumption thus conforming to the law. Within ten months from 2013 to 2014, there had been serious fatalities reported from this drug from four different countries. The first fatality was a 19-year-old male who had a 3.9 mg/L AH-7921 concentration of heart blood leading medical examiners to confirm the death was an opioid intoxication. In another case, a 22-year-old woman was found dead with a femoral blood to AH-7921 concentration of 450 μg/L.

A 2018 review of published case reports found a total of 14 cases, of which 13 resulted in death. The oral route of administration was reported in two cases, and most cases reported use of concomitant pharmaceutical agents. Postmortem autopsies found that pulmonary edema was the most common finding, with nine of the cases having heavier lungs. Overall, fatalities occurred with low and high concentrations of AH-7921 in femoral blood.

Legality

AH-7921 was made a Prohibited Substance (Schedule 9 of the Standard for the Uniform Scheduling of Medicines and Poisons) in Australia in May 2014. Although this amendment was repealed in June 2014, which simply means the amendment document ceases, but the actual scheduling is permanent as part of the main document (all SUSMP amendments cease after a few weeks). It may, however, still be a banned import.

AH-7921 has been illegal to distribute in Israel since December 2013.

In the UK, AH-7921 was included as a Class A drug in January 2015 as part of The Misuse of Drugs Act 1971 (Amendment) (No. 2) Order 2014.

In Brazil, AH-7921 has been an illegal drug since May 2015.

As of October 2015 AH-7921 is a controlled substance in China.

AH-7921 is banned in the Czech Republic.

In the United States, AH-7921 was placed into Schedule I of the Controlled Substances Act on May 16, 2016, due to its lack of medical use. Furthermore, any person who wishes to manufacture, distribute, import, export, research, and educate using the substance, must be registered by the Drug Enforcement Administration.

The Canadian Controlled Drugs and Substances Act was amended in 2016 to include the substance as a Schedule I substance. Possession without legal authority can result in maximum 7 years imprisonment. Further, Health Canada amended the Food and Drug Regulations in May, 2016 to classify AH-7921 as a restricted drug. Only those with a law enforcement agency, person with an exemption permit or institutions with Minister's authorization may possess the drug in Canada.

References

References

  1. (September 1973). "Proceedings: Anti-nociceptive effects in N-substituted cyclohexylmethylbenzamides". British Journal of Pharmacology.
  2. (July 1983). "Determination of receptors that mediate opiate side effects in the mouse". British Journal of Pharmacology.
  3. (November 1974). "1-(3,4-Dichlorobenzamidomethyl)cyclohexyldimethylamine and related compounds as potential analgesics". Journal of Medicinal Chemistry.
  4. "1-(3,4-Dichlorobenzamidomethyl)-cyclohexyldimethylamine".
  5. "2016 - Final Order: Placement of AH-7921 Into Schedule I".
  6. (2015). "AH-7921: the list of new psychoactive opioids is expanded". Forensic Toxicology.
  7. (2017-06-30). "An Expanding World of Novel Psychoactive Substances: Opioids". Frontiers in Psychiatry.
  8. (10 January 2017). "The New Wave of Designer Drugs". Concordia University, St. Paul Online.
  9. (August 2016). "Metabolic characterization of AH-7921, a synthetic opioid designer drug: in vitro metabolic stability assessment and metabolite identification, evaluation of in silico prediction, and in vivo confirmation". Drug Testing and Analysis.
  10. "AH-7921: 3,4-dichloro-N-[[1-(dimethylamino)cyclohexyl]methyl]benzamide". U.S. National Library of Medicine.
  11. (July 2013). "Two new-type cannabimimetic quinolinyl carboxylates, QUPIC and QUCHIC, two new cannabimimetic carboxamide derivatives, ADB-FUBINACA and ADBICA, and five synthetic cannabinoids detected with a thiophene derivative α-PVT and an opioid receptor agonist AH-7921 identified in illegal products". Forensic Toxicology.
  12. (12 November 2015). "Two horses test positive for designer drug". [[Racing Post]].
  13. (May 2014). "A fatality involving AH-7921". Journal of Analytical Toxicology.
  14. (August 2017). "Two fatalities associated with synthetic opioids: AH-7921 and MT-45". Forensic Science International.
  15. (July 2018). "AH-7921: A review of previously published reports". Proceedings.
  16. (May 2014). "Final decisions and reasons for decisions by delegates of the Secretary to the Department of Health". Commonwealth of Australia.
  17. (19 May 2014). "Poisons Standard Amendment No. 2 of 2014". Commonwealth of Australia.
  18. "פקודת הסמים המסוכנים נוסח חדש, תשל"ג -1973".
  19. "The Misuse of Drugs Act 1971 (Amendment) (No. 2) Order 2014". Legislation.gov.uk.
  20. "Resolução da Diretoria Colegiada - RDC nº 87 de 28/06/2016".
  21. (27 September 2015). "关于印发《非药用类麻醉药品和精神药品列管办法》的通知". China Food and Drug Administration.
  22. "Látky, o které byl doplněn seznam č. 4 psychotropních látek (příloha č. 4 k nařízení vlády č. 463/2013 Sb.)". Ministerstvo zdravotnictví.
  23. (14 April 2016). "Schedules of Controlled Substances: Placement of AH-7921 Into Schedule I". U.S. Department of Justic.
  24. (June 2016). "Regulations Amending the Food and Drug Regulations (Parts G and J — Lefetamine, AH-7921, MT-45 and W-18)". The Government of Canada.
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