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Cytochrome P450 inhibition potential of new psychoactive substances of the tryptamine class

Dinger, J, Woods, C, Brandt, SD, Meyer, MR and Maurer, HH (2016) Cytochrome P450 inhibition potential of new psychoactive substances of the tryptamine class. Toxicology Letters, 241. pp. 82-94. ISSN 0378-4274

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New psychoactive substances (NPS) are not tested for their cytochrome P450 (CYP) inhibition potential before consumption. Therefore, this potential was explored for tryptamine-derived NPS (TDNPS) including alpha-methyl tryptamines (AMTs), dimethyl tryptamines (DMTs), diallyl tryptamines (DALTs), and diisopropyl tryptamines (DiPTs) using test substrates preferred by the Food and Drug Administration in a cocktail assay. All tested TDNPS with the exception of DMT inhibited CYP2D6 activity with IC50 values below 100 μM. DALTs inhibited CYP2D6 activity similar to paroxetine and quinidine and CYP1A2 activity comparable to fluvoxamine. 5-Methoxy-N,N-diallyltryptamine reduced in vivo the caffeine metabolism in rats consistent with in vitro results. Five of the AMTs also inhibited CYP1A2 activity comparable to amiodarone. AMT and 6-F-AMT inhibited CYP2A6 activity in the range of the test inhibitor tranylcypromine. CYP2B6 activity was inhibited by 19 tryptamines, but weakly compared to efavirenz. CYP2C8 activity was inhibited by five of the tested TDNPS and three showed values comparable to trimethoprim and gemfibrozil. Six tryptamines inhibited CYP2C9 and seven CYP2C19 activities comparable to fluconazole and chloramphenicol, respectively. Nineteen compounds showed inhibition of CYP2E1 and 18 of CYP3A activity, respectively. These results showed that the CYP inhibition by TDNPS might be clinically relevant, but clinical studies are needed to explore this further.

Item Type: Article
Uncontrolled Keywords: 0502 Environmental Science And Management, 1115 Pharmacology And Pharmaceutical Sciences
Subjects: R Medicine > RM Therapeutics. Pharmacology
R Medicine > RS Pharmacy and materia medica
Divisions: Pharmacy & Biomolecular Sciences
Publisher: Elsevier
Date Deposited: 10 Mar 2016 09:42
Last Modified: 03 Aug 2022 08:00
DOI or ID number: 10.1016/j.toxlet.2015.11.013
URI: https://researchonline.ljmu.ac.uk/id/eprint/2402
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