dgs-info, Extraausgabe vom 21. September 2016

Liebe Kolleginnen und Kollegen,
Anliegende Warnmeldung der Europäischen Beobachtungsstelle für Drogen und Drogensucht (EMCDDA) hat uns erreicht, die wir hiermit zur Kenntnisnahme und Beachtung an unsere Mitglieder weiterleiten.

Der Vorstand der DGS
Konrad Isernhagen

 


Liebe Kolleginnen und Kollegen,

Anbei finden Sie eine Warnmeldung des Early Warning Systems der EMCDDA. In
Schweden gab es im Zeitraum von April bis August 23 Todesfälle die mit der Substanz Acryloyl Fentanyl in Zusammenhang stehen.

Es handelt sich hierbei um ein Opioid, mit dem chemischen Namen: N-(1-phenethylpiperidin-4-yl)-N-phenylacrylamide.
Unter Anderem wird die Substanz auch acrylfentanyl, ACF und 1-phenethyl-4-Nacryloylanilinopiperidine genannt.

Die Substanz wurde dem EWS das erste Mal im Juli 2016 von Schweden und Dänemark gemeldet.

In 8 der 23 Todesfällen war Acryloyl Fentanyl die Todesursache oder war an dem Tod beteiligt; in 2 Fällen wurde von dem Verstorbenen nur Acryloyl Fentanyl eingenommen.

Weitere 15 Fälle werden noch begutachtet. In allen Fällen wurde Acryloyl Fentanyl in biologischen Proben festgestellt.

Bei den Verstorbenen handelt es sich um 4 Frauen und 19 Männer zwischen 22 und 54 Jahren alt (Durchschnitt 33, Median 29). Zu den Umständen der Todesfälle ist nichts weiter bekannt, außer dass in zwei Fällen der Tod plötzlich eingesetzt hat, bei einer Person nachdem diese mit Freunden die Substanz in Form eines Nasensprays eingenommen hatte.

Arcyloyl Fentanyl ist strukturell mit dem … Opioid Fentanyl verwandt. Bisher liegen keine Studien zur Pharmakokinetik und Pharmakodynamik in Menschen vor. Die wenigen Studien an Tieren gehen davon aus, dass Arcyloyl Fentanyl ein potentes Opioidanalgetikum ist, dessen Effekte länger andauern als die von Fentanyl und Morphium.

Aufgrund der strukturellen Ähnlichkeit zu Fentanyl, wird vermutet, dass auch in Fällen einer Acryloyl Fentanyl Intoxikation Naloxone als wirksames Gegenmittel eingesetzt werden kann.
... Daten zur Verbreitung und der Konsumenteneigenschaften sind bisher nicht bekannt.

Im Anhang finden Sie die offizielle Meldung der EMCDDA.
Sollten Ihnen noch Informationen zum Konsum von Acryloyl Fentanyl bekannt sein, teilen Sie diese bitte dem EWS mit.

Wie immer bitte ich Sie bei beim Teilen der Alerts zu bedenken, welche der in dieser E-Mail enthaltenen Informationen für die jeweiligen Zielgruppen angemessen sind!

Vielen Dank für Ihre Mithilfe,
beste Grüße

Tessa-Virginia Hannemann
Tessa-Virginia Hannemann, M.Sc.
Wissenschaftliche Mitarbeiterin/Research Assistant
PHAR-MON NPS
Institut für Therapieforschung / Parzivalstraße 25, 80804, München / www.ift.de
Tel +49 (0) 89 360804 36 / E-Mail: hannemann@ift.de
IFT Institut für Therapieforschung gem. Gesellschaft mbH / Registergericht München HRB 46395

 

1. Read me first

23 analytically confirmed deaths associated with the synthetic opioid acryloyl fentanyl (also referred to as acrylfentanyl) have been reported by Sweden. The deaths occurred between April and August 2016. Acryloyl fentanyl caused or contributed to the death in the 8 cases for which a cause of death has already been determined.
Acryloyl fentanyl was formally notified to the EU EWS Network in July 2016 and has been detected in 2 Member States (Denmark and Sweden).

This alert should be read in conjunction with:

  • the formal notification for acryloyl fentanyl issued on 07-07-2016:
    (https://ednd.emcdda.europa.eu/html.cfm/index7246EN.html?SUB_ID=617&detail)
  • the related press release by the Swedish National Board of Forensic Medicine:
    (http://rmv.se/index.php?id=433)
    The purpose of this alert is to:
  • inform you that 23 confirmed deaths associated with acryloyl fentanyl have recently
    occurred in Sweden; and,
  • request that you report any information you may have on acryloyl fentanyl.
    Please report any additional information to ews@emcdda.europa.eu
    Should you decide to issue risk communications aimed at users following from this alert, please note that you should avoid using terms such as 'potent' or 'strong' to describe acryloyl fentanyl, as such terms may cause users to actively seek it out.

2. Data use restrictions

As with all alerts transmitted by the EU EWS, please remember that they may contain information that could be regarded as sensitive. Should you provide some of the information in this alert to your wider network we would ask that you exercise your best judgement on what information needs to be provided. If you have any questions in this respect, please contact ews@emcdda.europa.eu.

3. Details of the event(s)

The EMCDDA has received reports of 23 deaths associated with acryloyl fentanyl. The deaths occurred between April and August 2016 in Sweden. The presence of acryloyl fentanyl was analytically confirmed in all the cases from biological samples taken from the deceased.
The decedents were aged 22 to 54 years old (mean 33, median 29); 4 were female, 19 were male. The cause of death is known for 8 cases: acryloyl fentanyl was the cause of death or a contributing factor in all of them; the remaining 15 cases are still under investigation.
Acryloyl fentanyl was the only substance consumed in 2 out of 23 deaths.
No details are known regarding the source of the substance or the route of administration except for one case where the death occurred after the person consumed acryloyl fentanyl with friends using a nasal spray. In at least 2 cases the deaths were said to have occurred “suddenly”.

4. Detections by the EU EWS Network

Formal notification
On 16 June 2016 the Danish FP reported a seizure of 1 capsule containing a white to pale yellow powder ‘seized’ on 11 May 2016 by the Department of Forensic Psychiatry of the Aalborg Psychiatric Hospital. Following from this report, acryloyl fentanyl was formally notified by the EMCDDA on 7 July 2016.

Seizures
No other seizures of acryloyl fentanyl have been reported by the EU EWS.

5. Names of substance and other identifiers

  • IUPAC name: N-(1-phenethylpiperidin-4-yl)-N-phenylacrylamide
  • Common name: Acryloyl fentanyl
  • Other names: acrylfentanyl, ACF, 1-phenethyl-4-N-acryloylanilinopiperidine
  • CAS Registry number: 79279-03-1 (hydrochloride)

6. Substance classification

Opioid

7. Chemistry and analysis

Acryloyl fentanyl is structurally related to the internationally controlled opioid fentanyl (Schedule I of the 1961 United Nations Single Convention On Narcotic Drugs). Their close structural similarity implies that the GC-MS of both substances may be very similar, with a mass difference of M-2 for the base peak (m/z 243 for acryloyl fentanyl). Literature sources have suggested that LC-MS/MS or equivalent techniques are recommendable to identify acryloyl fentanyl, as only a limited number of fentanyl assays have been critically validated for clinical use [1]. Immuno-assays for fentanyl may cross-react with acryl fentanyl.
Based on the analysis of the impurities found in the sample of acryloyl fentanyl detected in Denmark in May 2016, the substance may have been synthesised using a modification of the ‘Siegfried method’ for the synthesis of fentanyl. N-phenyl-1-(2-phenylethyl)piperidin-4-4amine (ANPP), a synthetic precursor which can also be used for the synthesis of fentanyl (and other related opioids) was also found in the sample [1].
Analytical data (GC-MS, HR-MS QTOF, HP-MS MALDI-TOF and NMR) is available in the scientific literature [1] and in the EDND.
https://ednd.emcdda.europa.eu/html.cfm/index7246EN.html?SUB_ID=617&detail
Acryloyl fentanyl has an acrylate moiety, which can in theory react under certain conditions to form polymers. At present, it is unknown if this affects the stability of the substance insolutions (such as the ones used in nasal spray formulations).

8. Pharmacology and toxicology

No data is available on the pharmacokinetic and pharmacodynamics properties of acryloyl fentanyl in humans. …
The available animal studies and the structural similarity between fentanyl and acryloyl fentanyl, suggest that naloxone may behave as an antidote to acryloyl fentanyl intoxications.
Fentanyl is a … opioid which may cause respiratory depression, bradycardia and
hypotension [5]. It has been established that the typical adverse effects associated with fentanyl can be reversed by naloxone [5].
As an acrylate, acryloyl fentanyl can potentially behave like a Michael-acceptor and
irreversibly bind to opioid receptors; animal studies by Marianoff et al., however, have found no evidence of this [4].

9. Epidemiology

What is the availability of acryloyl fentanyl on the drug market?
Acryloyl fentanyl is the 14th derivative of fentanyl to be formally notified to the EU EWS Network since 2012, and the 4th to be notified this year. ….
Acryloyl fentanyl has been sold as powders and in nasal spray formulations.

Who uses acryloyl fentanyl and why?
There is no data on the prevalence of use of acryloyl fentanyl. Given its pharmacology, acryloyl fentanyl may be actively sought by those looking for substitutes for opioids. These may include individuals who use illicit opioids, such as heroin and/or prescription opioids.

10. Further information

Further information on this substance is available on the EDND profile:
https://ednd.emcdda.europa.eu/html.cfm/index7246EN.html?SUB_ID=617&detail

11. Acknowledgements

We would like to acknowledge the Swedish and the Danish Reitox National Focal Points
who contributed to the data on acryloyl fentanyl which were used in this alert.

12. Attachments

5
The printer friendly version (.pdf) of this alert is attached to this email.

13. References

[1] Breindahl T et al. Identification of a new psychoactive substance in seized material: the synthetic opioid N-phenyl-N-[1-(2-phenethyl)piperidin-4-yl]prop-2-enamide (Acrylfentanyl). Drug Test. Anal. 2016; doi: 10.1002/dta.2046.
[2] Zhu YC, et al. Studies on potent analgesics 2. Synthesis and analgesic activity of the derivatives. Acta Pharm Sin. 1981;16(3): 97–104. [in Chinese]
[3] Essawi MYH. Fentanyl analogues with a modified propanamido group as potential affinity labels: synthesis and in vivo activity. Pharmazie 1999;54(4):307–8.
[4] Maryanoff BE, et al. Potential Affinity Labels for the Opiate Receptor Based on Fentanyl and Related Compounds. J Med Chem. 1982;25(8):913–19.
[5] Bowdle, TA. Adverse effects of opioid agonists and agonist-antagonists in anaesthesia. Drug Saf. 1998; 19(3):173-89

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Rita Jorge, PhD
Scientific analyst
Action on new drugs sector — Supply reduction and new drugs unit
Tel. (351) 211 21 02 10
European Monitoring Centre for Drugs and Drug Addiction (EMCDDA)
Praça Europa 1, Cais do Sodré, 1249-289 Lisbon, Portugal • www.emcdda.europa.eu