Corrigendum to “Measuring inhibition of monoamine reuptake transporters by new psychoactive substances (NPS) in real-time using a high-throughput, fluorescence-based assay” [Toxicology in Vitro (2017) 60–71](S0887233317301261)(10.1016/j.tiv.2017.05.010)

Anne Zwartsen, Anouk H. A. Verboven, Regina G. D. M. van Kleef, Fiona M. J. Wijnolts, Remco H. S. Westerink, Laura Hondebrink

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Abstract

The authors regret that incorrect IC 50 values were listed in the article due to faulty use of the software calculating these values. In this corrigendum, changed IC 50 values are provided in the tables (table 1, 2, 3 and supplemental table 1 and 2) in blue text. Changed IC 50 values in the main text are indicated by bold text. These alterations did not affect data interpretation, or the conclusions drawn. The authors would like to apologise for any inconvenience caused. Corrected Table 1. Inhibition of monoamine transporter uptake by illicit drugs, NPS and fluoxetine. [Table presented] 3. Results 3.2 Drug-induced monoamine transporter uptake inhibition (pre-incubation with the fluorescent substrate) Exposure to NPS and commonly used illicit drugs concentration-dependently inhibited uptake of monoamine transporters following 12 min of exposure (Fig. 4; Table 1). Cocaine potently inhibited all three transporters with IC 50 values of 1.0–1.4 μM. α-PVP was over ten times more potent than cocaine in inhibiting uptake of hDAT and hNET (IC 50 0.08 and 0.07 μM, respectively), although α-PVP only weakly inhibited hSERT. DL-amphetamine also potently inhibited hNET and to a lesser extent hDAT, but only weakly inhibited hSERT. Stimulants that also are entactogenic showed a somewhat higher potency for inhibiting hSERT (IC 50 30–200 μM) compared to α-PVP and DL-amphetamine, but most potently inhibited hNET (IC 50 0.8–4.9 μM) and to a lesser extent hDAT (IC 50 4.6–40 μM). The hallucinogenic compounds (25B-NBOMe, 25I-NBOMe and MXE) potently inhibited hSERT (IC 50 2.2–4.9 μM) and to a lesser extent hNET (IC 50 11–15 μM). These compounds inhibited hDAT only moderately (IC 50 24–99 μM). The hallucinogen 2C-B also preferentially inhibited hSERT, although with a ~10-fold higher IC 50 compared to 25B-NBOMe and 25I-NBOMe. As expected, the selective serotonin reuptake inhibitor (SSRI) antidepressant fluoxetine potently inhibited hSERT (IC 50 0.1 μM), whereas IC 50 values for hNET and hDAT were respectively ~50- and ~400-fold higher. 3.5 Estimated drug concentration in the brain Almost all compounds inhibit at least one of the transporters at concentrations relevant for humans, except the NBOMe's and 2C-B. Corrected Table 2. Estimated brain concentrations of commonly used illicit drugs, NPS and fluoxetine compared to their potency to inhibit monoamine transporters. [Table presented] References for serum concentrations: a Javaid et al., 1978; b Cone, 1995; c Jeffcoat et al., 1989; d Isenschmid et al., 1992; e Jenkins et al., 2002; f Lee et al., 2000; g Angrist et al., 1987; h Röhrich et al., 2012; i Eiden et al., 2013; j Wright and Harris, 2016; k de la Torre et al., 2000; l Vevelstad et al., 2012; m Elliot and Evans, 2014; n Adamowicz et al., 2014; o Adamowicz et al., 2016; p Ho et al., 2013; q Polkis et al., 2014a; r Laskowski et al., 2015; s Polkis et al., 2013; t Wood et al., 2012; u Shields et al., 2012; v Orsulak et al., 1988; w Rambourg Schepens, 1996, x Johansen and Hansen, 2012, y Holmgren et al., 2008. References for BPF calculation: 1 Brajkovic et al., 2016; 2 Bystrowska et al., 2012; 3 Rivière et al., 2000; 4 White et al., 2014; 5 Hendrickson et al., 2006; 6 Sykutera et al., 2015; 7 Hasegawa et al., 2014; 8 Mueller et al., 2009; 9 Pálenícek et al., 2011; 10 Rohanová et al., 2008; 11 Polkis et al., 2014b; 12 Horsley et al., 2016; 13 Karson et al., 1993; 14 Holladay et al., 1998; 15 Shiue et al., 1993. 4. Discussion: Paragraph 2: Importantly, inhibition of monoamine transporters was detected at concentrations relevant for human exposure. For almost all substances, the IC 50 value for at least one of the transporters was in range of the estimated brain concentration, while five substances likely affect more than one transporter at estimated brain concentrations. Even the selective serotonin re-uptake inhibitor fluoxetine inhibits both hSERT (IC 50 0.1 μM) and hNET (IC 50 5.8 μM) at estimated therapeutic brain concentrations, in line with other literature (Karson et al., 1993; Renshaw et al., 1992; Komoroski et al., 1994; Strauss et al., 2002; Henry et al., 2005; Strauss and Dager, 2001). Corrected Table 3. Inhibition of monoamine transporter uptake (IC 50, μM) by illicit drugs, NPS and fluoxetine compared to literature. [Table presented] References: a Marona-Lewicka et al., 1995; b Hyttel, 1982; c Cozzi et al., 1999; d Martel and Keating, 2003; e Meltzer et al., 2006; f Nagai et al., 2007; g Jørgenson et al., 2008; h Yoon et al., 2009; i Eshleman et al., 2013; j Baumann et al., 2013; k Rosenauer et al., 2013; l Simmler et al., 2013; m Simmler et al., 2014; n Marusich et al., 2014; o Rickli et al., 2015a; p Rickli et al., 2015b; q Rickli et al., 2015c

Original languageEnglish
Article number104631
JournalToxicology in Vitro
Volume62
DOIs
Publication statusPublished - Feb 2020

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