Emerging Drugs of Abuse

Nelson, M. E.; Bryant, Sean M.; Aks, Steven E.

doi:10.1016/j.emc.2013.09.001

Cited by 110 publications

(113 citation statements)

References 149 publications

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“…Emerging toxins may also affect post-resuscitation care. Synthetic marijuana (Bspice^) and synthetic cathinones (Bbath salts^) are both associated with deaths due to hyperthermia, seizures, and direct cardiovascular toxicity [17,18]. There is no published experience with TH and these more novel toxins.…”

Section: Discussionmentioning

confidence: 99%

Outcomes in Cardiac Arrest Patients due to Toxic Exposure Treated with Therapeutic Hypothermia

et al. 2016

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The incidence and outcome of patients who undergo therapeutic hypothermia (TH) after toxin-induced cardiac arrest (TICA) is not previously described. Our study aimed to describe the incidence, epidemiologic characteristics, and outcomes of patients who experience TICA in a dedicated clinical pathway for post-cardiac arrest care between November 2007 and February 2013. All patients were treated in an evidencebased clinical pathway that included TH. Database and medical records were independently reviewed by investigators to ascertain TICA. TICA was defined as cardiac arrest (CA) directly and immediately caused by a xenobiotic exposure. All patients were enrolled at Carolinas Medical Center, an urban 874-bed teaching hospital that serves as a regional cardiac resuscitation center. All patients were adult victims of cardiac arrest who had obtained return of spontaneous circulation and were enrolled in a clinical pathway for post-cardiac arrest care that included TH. Three hundred eighty-nine patients underwent treatment following CA during the study period and 48 (12 %) were deemed TICA. Patients who suffered TICA were slightly younger, less likely to have an initial shockable rhythm, and less likely to receive bystander CPR as compared to non-toxic cases. TICA accounted for a significant proportion of patients in this study. Additional, larger studies are needed to fully elucidate the optimal role for TH in TICA.

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Section: Discussionmentioning

confidence: 99%

Outcomes in Cardiac Arrest Patients due to Toxic Exposure Treated with Therapeutic Hypothermia

et al. 2016

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“…12,13 Despite their predominance in the US, these two drugs are not the most widely abused amphetamine analogues in all countries. 14,15 In Saudi Arabia it has been estimated that 40% of drug users between ages 12–22 are addicted to fenethylline.…”

Section: Mainmentioning

confidence: 99%

Vaccine-driven pharmacodynamic dissection and mitigation of fenethylline psychoactivity

Wenthur

Zhou

Janda

2017

Nature

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SUMMARY PARAGRAPH Fenethylline, also known as Captagon, is a synthetic psychoactive stimulant that has recently been linked to substance use disorder and ‘pharmacoterrorism’ in the Middle East.1–4 Although fenethylline shares a common phenethylamine core with other amphetamine-type stimulants, it additionally incorporates a covalently-linked xanthine moiety into its parent structure.5,6 These independently-active pharmacophores are liberated during metabolism, resulting in a structurally-diverse chemical mixture being deployed to the central nervous system.7–9 Although fenethylline’s psychoactive properties have been reported to differ from other synthetic stimulants, the in vivo chemical complexity it manifests upon ingestion has impeded efforts to unambiguously identify the specific species responsible for these effects.10,11 Here we develop a ‘dissection through vaccination’ approach, called DISSECTIV, to mitigate fenethylline’s psychoactivity and show that its rapid-onset and distinct psychoactive properties are facilitated by functional synergy between theophylline and amphetamine. Our results demonstrate that incremental vaccination against single chemical species within a multi-component mixture can be used to uncover emergent properties arising from polypharmacologic activity. We anticipate that DISSECTIV will be employed to expose unidentified active chemical species and illuminate pharmacodynamic interactions within other chemically complex systems, such as those found in counterfeit or illegal drug preparations, post-metabolic tissue samples, and natural product extracts.

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“…Because deuterium-labeled analogs of compounds risk having a small amount of signal associated with the non-deuterium-labeled drug, we chose to minimize the concentrations of the internal standards. The standards used in this study had an isotopic purity of 90.95% D 8 Table I summarizes the data collected during the method validation experiments, which followed FDA guidance (35). Values were deemed acceptable based on % RSD and % error of ≤15% for all QC points except LOQ, where ≤20% was allowed (35).…”

Section: Methods Developmentmentioning

confidence: 99%

“…These compounds have similar pharmacology to cocaine, the amphetamines, and 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy"), with desirable effects that include alertness, euphoria, and sexual arousal (1,(6)(7)(8)(9). Case reports indicate that the effects from synthetic cathinones initiate within 30-45 min following use, but can linger for many hours or days (1).…”

Section: Introductionmentioning

confidence: 99%

Quantification of Synthetic Cathinones in Rat Brain Using HILIC–ESI-MS/MS

et al. 2016

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The abuse of synthetic cathinones, formerly marketed as "bath salts", has emerged over the last decade. Three common drugs in this class include 3,4-methylenedioxypyrovalerone (MDPV), 4-methylmethcathinone (mephedrone), and 3,4-methylenedioxymethcathinone (methylone). An LC-MS/MS method has been developed and validated for the simultaneous quantification of MDPV, mephedrone, and methylone in brain tissue. Briefly, MDPV, mephedrone, methylone, and their deuterium-labeled analogs were subjected to solid phase extraction (SPE) and separated using an HILIC Silica Column. The HPLC was coupled to a Shimadzu IT-TOF (ion trap-time of flight) system with the electrospray source running in positive mode (+ESI). The method was validated for precision, accuracy, and extraction efficiency. All inter-day and intra-day % RSD (percent relative standard deviation) and % error values were less than 15% and extraction efficiency exceeded 80%. These conditions allowed for limits of detection of 1ng/mL for MDPV, and 5 ng/mL for both mephedrone and methylone. The limits of quantification were determined to be 5ng/mL for MDPV and 10 ng/mL for mephedrone and methylone. The method was utilized to evaluate the pharmacokinetics of these drugs in adult male rats following administration of a drug cocktail including MDPV, mephedrone, and methylone. All three compounds reached peak concentrations in the brain within 15 min. Although methylone and mephedrone were administered at the same dose, the peak concentration (C max ) of mephedrone in the brain was significantly higher than that for methylone, as was the area under the curve (AUC). In summary, this quick and sensitive method for measuring synthetic cathinones may be used for future pharmacokinetic investigations of these drugs in target tissue.

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Emerging Drugs of Abuse

Cited by 110 publications

References 149 publications

Outcomes in Cardiac Arrest Patients due to Toxic Exposure Treated with Therapeutic Hypothermia

Outcomes in Cardiac Arrest Patients due to Toxic Exposure Treated with Therapeutic Hypothermia

Vaccine-driven pharmacodynamic dissection and mitigation of fenethylline psychoactivity

Quantification of Synthetic Cathinones in Rat Brain Using HILIC–ESI-MS/MS

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