In vitro functional characterization of a panel of non-fentanyl opioid new psychoactive substances
- Author
- Marthe Vandeputte (UGent) , Annelies Cannaert (UGent) and Christophe Stove (UGent)
- Organization
- Project
- Abstract
- The landscape of new psychoactive substances (NPS) is constantly evolving, with new compounds entering the illicit drug market at a continuous pace. Of these, opioid NPS form a threat given their high potency and prevalence. Whereas previously, the use of fentanyl and fentanyl derivatives was the main point of attention, legislations have reacted accordingly, whichmay have been a driving force towards the (ab)use of alternative µ-opioid receptor (MOR) agonists. In contrast to fentanyl (analogues), details on these novel non-fentanyl opioid NPS are scarce. We investigated the biological activity of a panel of 11 ‘alternative’, newly emerging MOR agonists (2-methyl-AP-237, AP-237, bromadol, brorphine, butorphanol, isotonitazene, mitragynine, 7-OH-mitragynine, MT-45, piperidylthiambutene, and tianeptine) using two closely related in vitro MOR activation bio-assays, monitoring either G protein (mini-Gi), or β-arrestin2 (βarr2) recruitment. Activity profles were obtained for all tested compounds, with values for potency (EC50) ranging from 1.89 nM (bromadol) to>3 µM (AP-237 and tianeptine). Bromadol, brorphine, isotonitazene, piperidylthiambutene, and tianeptine had the highest efcacy (Emax) values, exceeding that of the reference compound hydromorphone≥1.3-fold (βarr2 assay) and>2.6-fold (mini-Gi assay). Information on the recruitment of two distinct signaling molecules additionally enabled evaluation of biased agonism; none of the evaluated opioids being signifcantly biased. Taken together, this study is the frst to systematically investigate the in vitro biological activity of a diverse panel of emerging non-fentanyl opioid NPS at MOR. Given the known danger of (fatal) intoxications with many opioid NPS, it is important to continuously monitor and characterize newly emerging compounds.
- Keywords
- New psychoactive substances (NPS), Synthetic opioids, Non-fentanyl opioids, Characterization, µ-Opioid receptor, Bio-assay, 1-SUBSTITUTED 4-(1, 2-DIPHENYLETHYL)PIPERAZINE DERIVATIVES, DRUG, PHARMACOLOGY, MITRAGYNINE, ALKALOIDS, EFFICACY, AGONIST
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-8687070
- MLA
- Vandeputte, Marthe, et al. “In Vitro Functional Characterization of a Panel of Non-Fentanyl Opioid New Psychoactive Substances.” ARCHIVES OF TOXICOLOGY, vol. 94, no. 11, 2020, pp. 3819–30, doi:10.1007/s00204-020-02855-7.
- APA
- Vandeputte, M., Cannaert, A., & Stove, C. (2020). In vitro functional characterization of a panel of non-fentanyl opioid new psychoactive substances. ARCHIVES OF TOXICOLOGY, 94(11), 3819–3830. https://doi.org/10.1007/s00204-020-02855-7
- Chicago author-date
- Vandeputte, Marthe, Annelies Cannaert, and Christophe Stove. 2020. “In Vitro Functional Characterization of a Panel of Non-Fentanyl Opioid New Psychoactive Substances.” ARCHIVES OF TOXICOLOGY 94 (11): 3819–30. https://doi.org/10.1007/s00204-020-02855-7.
- Chicago author-date (all authors)
- Vandeputte, Marthe, Annelies Cannaert, and Christophe Stove. 2020. “In Vitro Functional Characterization of a Panel of Non-Fentanyl Opioid New Psychoactive Substances.” ARCHIVES OF TOXICOLOGY 94 (11): 3819–3830. doi:10.1007/s00204-020-02855-7.
- Vancouver
- 1.Vandeputte M, Cannaert A, Stove C. In vitro functional characterization of a panel of non-fentanyl opioid new psychoactive substances. ARCHIVES OF TOXICOLOGY. 2020;94(11):3819–30.
- IEEE
- [1]M. Vandeputte, A. Cannaert, and C. Stove, “In vitro functional characterization of a panel of non-fentanyl opioid new psychoactive substances,” ARCHIVES OF TOXICOLOGY, vol. 94, no. 11, pp. 3819–3830, 2020.
@article{8687070, abstract = {{The landscape of new psychoactive substances (NPS) is constantly evolving, with new compounds entering the illicit drug market at a continuous pace. Of these, opioid NPS form a threat given their high potency and prevalence. Whereas previously, the use of fentanyl and fentanyl derivatives was the main point of attention, legislations have reacted accordingly, whichmay have been a driving force towards the (ab)use of alternative µ-opioid receptor (MOR) agonists. In contrast to fentanyl (analogues), details on these novel non-fentanyl opioid NPS are scarce. We investigated the biological activity of a panel of 11 ‘alternative’, newly emerging MOR agonists (2-methyl-AP-237, AP-237, bromadol, brorphine, butorphanol, isotonitazene, mitragynine, 7-OH-mitragynine, MT-45, piperidylthiambutene, and tianeptine) using two closely related in vitro MOR activation bio-assays, monitoring either G protein (mini-Gi), or β-arrestin2 (βarr2) recruitment. Activity profles were obtained for all tested compounds, with values for potency (EC50) ranging from 1.89 nM (bromadol) to>3 µM (AP-237 and tianeptine). Bromadol, brorphine, isotonitazene, piperidylthiambutene, and tianeptine had the highest efcacy (Emax) values, exceeding that of the reference compound hydromorphone≥1.3-fold (βarr2 assay) and>2.6-fold (mini-Gi assay). Information on the recruitment of two distinct signaling molecules additionally enabled evaluation of biased agonism; none of the evaluated opioids being signifcantly biased. Taken together, this study is the frst to systematically investigate the in vitro biological activity of a diverse panel of emerging non-fentanyl opioid NPS at MOR. Given the known danger of (fatal) intoxications with many opioid NPS, it is important to continuously monitor and characterize newly emerging compounds.}}, author = {{Vandeputte, Marthe and Cannaert, Annelies and Stove, Christophe}}, issn = {{0340-5761}}, journal = {{ARCHIVES OF TOXICOLOGY}}, keywords = {{New psychoactive substances (NPS),Synthetic opioids,Non-fentanyl opioids,Characterization,µ-Opioid receptor,Bio-assay,1-SUBSTITUTED 4-(1,2-DIPHENYLETHYL)PIPERAZINE DERIVATIVES,DRUG,PHARMACOLOGY,MITRAGYNINE,ALKALOIDS,EFFICACY,AGONIST}}, language = {{eng}}, number = {{11}}, pages = {{3819--3830}}, title = {{In vitro functional characterization of a panel of non-fentanyl opioid new psychoactive substances}}, url = {{http://doi.org/10.1007/s00204-020-02855-7}}, volume = {{94}}, year = {{2020}}, }
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