Please use this identifier to cite or link to this item: doi:10.22028/D291-30906
Title: In vitro monoamine oxidase inhibition potential of alpha-methyltryptamine analog new psychoactive substances for assessing possible toxic risks
Author(s): Wagmann, Lea
Brandt, Simon D.
Kavanagh, Pierce V.
Maurer, Hans H.
Meyer, Markus R.
Language: English
Title: Toxicology Letters
Volume: 272
Pages: 84-93
Publisher/Platform: Elsevier
Year of Publication: 2017
Free key words: Alpha-methyltryptamine analog new psychoactive substances
Drugs of abuse
MAO inhibition
IC50 value
DDC notations: 500 Science
540 Chemistry
570 Life sciences, biology
Publikation type: Journal Article
Abstract: Tryptamines have emerged as new psychoactive substances (NPS), which are distributed and consumed recreationally without preclinical studies or safety tests. Within the alpha-methylated tryptamines, some of the psychoactive effects of the prototypical alpha-methyltryptamine (AMT) have been described decades ago and a contributing factor of its acute toxicity appears to involve the inhibition of monoamine oxidase (MAO). However, detailed information about analogs is scarce. Therefore, thirteen AMT analogs were investigated for their potential to inhibit MAO. An in vitro assay analyzed using hydrophilic interaction liquid chromatography–high resolution-tandem mass spectrometry was developed and validated. The AMT analogs were incubated with recombinant human MAO-A or B and kynuramine, a non-selective MAO substrate to determine the IC50 values. The known MAO-A inhibitors 5-(2-aminopropyl)indole (5-IT), harmine, harmaline, yohimbine, and the MAO-B inhibitor selegiline were tested for comparison. AMT and all analogs showed MAO-A inhibition properties with IC50 values between 0.049 and 166 μM, whereas four analogs inhibited also MAO-B with IC50 values between 82 and 376 μM. 7-Me-AMT provided the lowest IC50 value against MAO-A comparable to harmine and harmaline and was identified as a competitive MAO-A inhibitor. Furthermore, AMT, 7-Me-AMT, and nine further analogs inhibited MAO activity in human hepatic S9 fraction used as model for the human liver which expresses both isoforms. The obtained results suggested that MAO inhibition induced by alpha-methylated tryptamines might be clinically relevant concerning possible serotonergic and adrenergic effects and interactions with drugs (of abuse) particularly acting as monoamine reuptake inhibitors. However, as in vitro assays have only limited conclusiveness, further studies are needed.
DOI of the first publication: 10.1016/j.toxlet.2017.03.007
Link to this record: urn:nbn:de:bsz:291--ds-309061
ISSN: 0378-4274
Date of registration: 20-May-2020
Faculty: M - Medizinische Fakultät
Department: M - Experimentelle und Klinische Pharmakologie und Toxikologie
Professorship: M - Prof. Dr. Markus Meyer
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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