Fatal intoxications associated with the designer opioid AH-7921.

AH-7921 (3,4-dichloro-N-[(1-dimethylamino)cyclohexylmethyl]benzamide) is a designer opioid with ∼80% of morphine's µ-agonist activity. Over a 6-month period, we encountered nine deaths where AH-7921 was involved and detected in blood from the deceased. Shortly after the last death, on August 1 2013, AH-7921 was scheduled as a narcotic and largely disappeared from the illicit market in Sweden. AH-7921 was measured by a selective liquid chromatography-MS-MS method and the concentrations of AH-7921 ranged from 0.03 to 0.99 µg/g blood. Six of our cases had other drugs of abuse on board and most had other medications such as benzodiazepines, antidepressants and analgesics. However, the other medicinal drugs encountered were present in postmortem therapeutic concentrations and unlikely to have contributed to death. In addition to the parent compound, we identified six possible metabolites where two N-demethylated dominated and four mono-hydroxylated were found in trace amounts in the blood. In conclusion, deaths with AH-7921 seem to occur both at low and high concentrations, probably a result of different tolerance to the drug. Hence, it is reasonable to assume that no sharp dividing line exists between lethal and non-lethal concentrations. Further, poly-drug use did not seem to be a major contributing factor for the fatal outcome.

[1]  V. Auwärter,et al.  Characterization of the designer benzodiazepine diclazepam and preliminary data on its metabolism and pharmacokinetics. , 2014, Drug testing and analysis.

[2]  Y. Goda,et al.  Changes in the prevalence of new psychoactive substances before and after the introduction of the generic scheduling of synthetic cannabinoids in Japan. , 2014, Drug testing and analysis.

[3]  Y. N. A. Soh,et al.  An investigation of the stability of emerging new psychoactive substances. , 2014, Drug testing and analysis.

[4]  B. Levine,et al.  A fatality involving AH-7921. , 2014, Journal of analytical toxicology.

[5]  R. Glennon,et al.  Synthetic cathinones: chemical phylogeny, physiology, and neuropharmacology. , 2014, Life sciences.

[6]  M. Meyer,et al.  Dimethocaine, a synthetic cocaine analogue: studies on its in-vivo metabolism and its detectability in urine by means of a rat model and liquid chromatography–linear ion-trap (high-resolution) mass spectrometry , 2014, Analytical and Bioanalytical Chemistry.

[7]  R. Kronstrand,et al.  LC-QTOF-MS as a superior strategy to immunoassay for the comprehensive analysis of synthetic cannabinoids in urine , 2014, Analytical and Bioanalytical Chemistry.

[8]  B. Mégarbane,et al.  The large spectrum of pulmonary complications following illicit drug use: features and mechanisms. , 2013, Chemico-biological interactions.

[9]  V. Auwärter,et al.  Detection and identification of the designer benzodiazepine flubromazepam and preliminary data on its metabolism and pharmacokinetics. , 2013, Journal of mass spectrometry : JMS.

[10]  I. Ojanperä,et al.  Parenteral buprenorphine-naloxone abuse is a major cause of fatal buprenorphine-related poisoning. , 2013, Forensic science international.

[11]  Robert Kronstrand,et al.  Toxicological findings of synthetic cannabinoids in recreational users. , 2013, Journal of analytical toxicology.

[12]  V. Auwärter,et al.  Acute intoxication by synthetic cannabinoids--four case reports. , 2013, Drug testing and analysis.

[13]  G. Zlabinger,et al.  Toxicological profiles of selected synthetic cannabinoids showing high binding affinities to the cannabinoid receptor subtype CB1 , 2013, Archives of Toxicology.

[14]  Satoru Matsuda,et al.  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 , 2013, Forensic Toxicology.

[15]  L. Ström,et al.  Liquid chromatography/time-of-flight mass spectrometry analysis of postmortem blood samples for targeted toxicological screening , 2013, Analytical and Bioanalytical Chemistry.

[16]  V. Auwärter,et al.  Acute toxicity due to the confirmed consumption of synthetic cannabinoids: clinical and laboratory findings. , 2013, Addiction.

[17]  Burkhard Madea,et al.  Driving under the influence of synthetic cannabinoids (“Spice”): a case series , 2013, International Journal of Legal Medicine.

[18]  R. Kronstrand,et al.  An accidental fatal intoxication with methoxetamine. , 2013, Journal of analytical toxicology.

[19]  H. Druid,et al.  Toxicological and pathological findings in a series of buprenorphine related deaths. Possible risk factors for fatal outcome. , 2012, Forensic science international.

[20]  M Coppola,et al.  Synthetic cathinones: chemistry, pharmacology and toxicology of a new class of designer drugs of abuse marketed as "bath salts" or "plant food". , 2012, Toxicology letters.

[21]  R. Rothman,et al.  The Designer Methcathinone Analogs, Mephedrone and Methylone, are Substrates for Monoamine Transporters in Brain Tissue , 2012, Neuropsychopharmacology.

[22]  E. Vuori,et al.  Benzodiazepines and alcohol are associated with cases of fatal buprenorphine poisoning , 2011, European Journal of Clinical Pharmacology.

[23]  R. Kronstrand,et al.  Unintentional fatal intoxications with mitragynine and O-desmethyltramadol from the herbal blend Krypton. , 2011, Journal of analytical toxicology.

[24]  N. Ferreirós,et al.  Monitoring of herbal mixtures potentially containing synthetic cannabinoids as psychoactive compounds. , 2010, Journal of mass spectrometry : JMS.

[25]  M. van Hage,et al.  Pathogenic role of cardiac mast cell activation/degranulation, TNF-α, and cell death in acute drug-related fatalities , 2007, Vascular health and risk management.

[26]  K. Alkass,et al.  Evaluation of the role of abstinence in heroin overdose deaths using segmental hair analysis. , 2007, Forensic science international.

[27]  Olaf H Drummer,et al.  Validation of new methods. , 2007, Forensic science international.

[28]  S. Darke,et al.  Suicide among heroin users: rates, risk factors and methods. , 2002, Addiction.

[29]  R. Kronstrand.  Identification of N-methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine (MBDB) in urine from drug users. , 1996, Journal of analytical toxicology.

[30]  A. Shulgin,et al.  Ring‐substituted β‐methoxyphenethylamines: a new class of psychotomimetic agents active in man , 1985, The Journal of pharmacy and pharmacology.

[31]  A. Hayes,et al.  Determination of receptors that mediate opiate side effects in the mouse , 1983, British journal of pharmacology.

[32]  A. Shulgin.  Chemistry of phenethylamines related to mescaline. , 1979, Journal of psychedelic drugs.

[33]  D. N. Kellett,et al.  Proceedings: Anti-nociceptive effects in N-substituted cyclohexylmethylbenzamides. , 1973, British journal of pharmacology.

[34]  A. Shulgin,et al.  4-Bromo-2,5-dimethoxyphenylisopropylamine, a new centrally active amphetamine analog. , 1971, Pharmacology.