Pharmacokinetics, pharmacodynamics and toxicology of new psychoactive substances (NPS): 2C-B, 4-fluoroamphetamine and benzofurans

Lonkhuyzen, Johanna J. Nugteren–van; Riel, Antoinette van; Brunt, Tibor M.; Hondebrink, Laura

doi:10.1016/j.drugalcdep.2015.10.011

Cited by 44 publications

(38 citation statements)

References 77 publications

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“…Oral exposure like this is reported to be most frequent 1 In the four cases with concentrations in the range of 320 to 500 ng/mL 5,6 concentrations were higher than the C max found in the present study after ingestion of a dose of 100 mg ( Table 2) and were in the range of the C max values found after ingestion of the 150 mg dose, which confirms estimations on typical dosages (40-200 mg 1 ).…”

Section: Comparison Of 4-fa Concentrations With Literaturesupporting

confidence: 85%

“…In cases of suspected driving under the influence of drugs (DUID), 4‐FA concentrations were in 13 cases in median 0.021 (whole blood, range 0.006 to 0.43) mg/kg, 90.0 and 89.9 ng/mL and 350 and 475 ng/mL . In the four cases with concentrations in the range of 320 to 500 ng/mL concentrations were higher than the C max found in the present study after ingestion of a dose of 100 mg (Table ) and were in the range of the C max values found after ingestion of the 150 mg dose, which confirms estimations on typical dosages (40–200 mg). However, a rather low concentration has been found in an intoxication case with life threatening cardiotoxicity where only 4‐FA was detected (5 hours after ingestion 118 ng/mL).…”

Section: Discussioncontrasting

confidence: 51%

“…In the comparison with data from the present study, it must be considered that the study drug was applied dissolved in a drink. Oral exposure like this is reported to be most frequent but compared to nasal insufflation, absorption may have been slower and bioavailability may have been lower due to first‐pass metabolism. In cases of suspected driving under the influence of drugs (DUID), 4‐FA concentrations were in 13 cases in median 0.021 (whole blood, range 0.006 to 0.43) mg/kg, 90.0 and 89.9 ng/mL and 350 and 475 ng/mL .…”

Section: Discussionmentioning

confidence: 99%

“…1 In The Netherlands, it was one of the most consumed NPS in 2013. 1 To assess its adverse effects, a study with a small number of subjects using a typical dose of 4-FA was performed. 2 One aspect of the study was the investigation of the pharmacokinetic properties of 4-FA in humans for which only a few reports on the detection of the drug in human blood or serum exist.…”

Section: Introductionmentioning

confidence: 99%

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Pharmacokinetic properties of 4‐fluoroamphetamine in serum and oral fluid after oral ingestion

Toennes

Schneider

Pogoda

et al. 2019

Drug Testing and Analysis

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Introduction Each year, synthetic drugs occur in high numbers on the illicit drug market. But data on their pharmacology and toxicology are scarce. Therefore, a controlled study was performed to evaluate pharmacokinetic parameters of 4‐fluoroamphetamine (4‐FA) in humans and to compare it with effects. Methods Twelve subjects ingested 100 mg and five subjects also received 150 mg 4‐FA in a bitter lemon drink. Blood and oral fluid samples were taken during the following 12 hours and analyzed for 4‐FA and traces of amphetamine as impurity by liquid chromatography−tandem mass spectrometry (LC–MS/MS). Results For 12 hours after ingestion, the concentration‐time course of 4‐FA was similar to that of amphetamine with maximal concentrations appearing in serum after about 2 hours (in median 195 ng/mL after the 100 mg dose, range 155–316 ng/mL). The elimination half‐life was approximately 8–9 hours and shorter than that of amphetamine but it exhibited a marked variation (5.5–16.8 hours). In oral fluid, 4‐FA could also be detected for 12 hours and concentrations were higher than in serum. During the first 3 hours after ingestion concentrations were higher, most probably due to oral contamination. Serum concentrations in forensic cases were in the range of those observed in the present study suggesting dosages in recreational use in the range of those tested here. Conclusions The pharmacokinetic properties of 4‐FA are similar to that of amphetamine including a marked variation in elimination. However, recreational dosages may already exhibit prominent adverse effects and may even have life‐threatening consequences.

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Section: Comparison Of 4-fa Concentrations With Literaturesupporting

confidence: 85%

Section: Discussioncontrasting

confidence: 51%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Pharmacokinetic properties of 4‐fluoroamphetamine in serum and oral fluid after oral ingestion

Toennes

Schneider

Pogoda

et al. 2019

Drug Testing and Analysis

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“…The primary mode of action of 4‐FA is via inhibition and reversal of the plasma membrane monoamine reuptake transporters with 4‐FA having more potent effects on the serotonin (5‐HT) transporter and less pronounced effects on the norepinephrine and dopamine transporter compared with amphetamine (Hondebrink, Zwartsen, & Westerink, ; Nagai, Nonaka, & Satoh Hisashi Kamimura, ; Nugteren‐van Lonkhuyzen, van Riel, Brunt, & Hondebrink, ; Rickli, Hoener, & Liechti, ). 4‐FA also acts as a monoamine releaser and agonist of the 5‐HT 2A and 5‐HT 2B receptors (Hondebrink et al, ; Rickli et al, ).…”

Section: Introductionmentioning

confidence: 99%

Independent elevation of peripheral oxytocin concentrations and reduction in cognitive empathy during 4‐fluoroamphetamine intoxication

Dolder

Perna

Mason

et al. 2018

Human Psychopharmacology

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Objectives 4‐Fluoroamphetamine (4‐FA) is a novel psychoactive substance with a pharmacological profile and reported subjective effects (e.g., empathy) intermediate between 3,4‐methylenedioxymethamphetamine (MDMA) and amphetamine. Studies have shown that MDMA and amphetamine increase emotional empathy without affecting cognitive empathy; MDMA simultaneously leads to elevated levels of oxytocin, unrelated to its behavioral effects. The aim of the present study was to assess the reported enhancement of empathy by 4‐FA, to assess its effects on oxytocin, and to test potential associations between both. Methods Twelve healthy poly‐drug users were included in a double‐blind placebo‐controlled two‐way crossover study. Treatments were 4‐FA (100 mg) and placebo; empathy was assessed by means of the multifaceted empathy test, and blood samples were taken before and after treatment administration to determine oxytocin concentrations. Results 4‐FA reduced cognitive empathy, whereas emotional empathy was left unaffected. One hour after treatment, plasma oxytocin levels were significantly increased compared with placebo. Behavioral and hormonal effects were unrelated. Conclusion Although 4‐FA shares its pharmacological mechanism with MDMA and amphetamine, current findings seem to indicate that it affects empathy differently. The 4‐FA‐induced increase in oxytocin levels was independent of behavioral effects, which confirms previous findings that drug‐induced effects on peripheral oxytocin levels are not associated with empathy.

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Analysis of 4‐fluoroamphetamine in cerumen after controlled oral application

Meier

Petzel‐Witt

Schubert‐Zsilavecz

et al. 2020

Drug Testing and Analysis

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Cerumen was found to be a promising alternative specimen for the detection of drugs. In a pilot study, drugs of abuse were identified at a higher detection rate and a longer detection window in cerumen than in urine. In this study, cerumen from subjects was analyzed after they ingested the designer stimulant 4‐fluoroamphetamine (4‐FA) in a controlled manner. Methods Twelve subjects ingested placebo and 100 mg of 4‐FA. Five of them were also given 150 mg of 4‐FA in 150 mL Royal Club bitter lemon drink at least after 7 days. Cerumen was sampled using cotton swabs at baseline, 1 h after the ingestion of the drug and at the end of the study day (12 h). After extraction with ethyl acetate followed by solid‐phase extraction, the extracts were analyzed using liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS). Results and discussion In the cerumen of all 12 subjects, 4‐FA was detected 12 h after its ingestion; in most subjects, cerumen was detected after 1 h of ingestion, ranging from 0.06 to 13.90 (median 1.52) ng per swab. The detection of 4‐FA in cerumen sampled 7 days or more after the first dose suggested a long detection window of cerumen. Conclusions Cerumen can be successfully used to detect a single drug ingestion even immediately after the ingestion when a sufficient amount of cerumen is used.

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Pharmacokinetics, pharmacodynamics and toxicology of new psychoactive substances (NPS): 2C-B, 4-fluoroamphetamine and benzofurans

Cited by 44 publications

References 77 publications

Pharmacokinetic properties of 4‐fluoroamphetamine in serum and oral fluid after oral ingestion

Pharmacokinetic properties of 4‐fluoroamphetamine in serum and oral fluid after oral ingestion

Independent elevation of peripheral oxytocin concentrations and reduction in cognitive empathy during 4‐fluoroamphetamine intoxication

Analysis of 4‐fluoroamphetamine in cerumen after controlled oral application

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