TABLE 1.
Effect of tested mephedrone metabolites on monoamine transporter mediated uptake. IC50 values are represented in μM as the mean (95% confidence interval) obtained from non-linear regression. NET/DAT ratio = (DAT IC50)/(NET IC50). Values > 1 indicate greater NET selectivity. DAT/SERT ratio = (SERT IC50)/(DAT IC50). Values > 1 indicate greater DAT selectivity. In the right column is highlighted if the metabolites were detected (+), not detected (−) or not determined (n.d.) in the urine samples analyzed. Only syn- and anti-configurations could be separated.
| Compound | IC50 (µM) | Selectivity ratio | Detected in urine samples | |||
|---|---|---|---|---|---|---|
| DAT | NET | SERT | NET/DAT | DAT/SERT | ||
| Cocaine† Ilic et al. (2020) | 1.21 ± 0.8† (0.72–2.01) | 1.03† (0.53–2.00) | 8.7† (7.44–12.26) | 1.2 | 7.25 | n.d |
| D-Amphetamine† Ilic et al. (2020) | 3.60† (2.13–6.16) | 0.85† (0.56–1.08) | 151.4† (101.5–225.9) | 4 | 42.06 | n.d |
| Mephedrone# Niello et al. (2019) § Mayer et al. (2016b) | 3.01# (2.34–3.67) | 2.77§ (1.92–3.97) | 8.74# (6.74–10.73) | 1.09 | 2.90 | + |
| R-4-OH-MC | 19.83 (17.16–22.93) | 9.07 (7.69–10.69) | 678.1 (583.4–788.1) | 2.19 | 34.19 | − |
| S-4-OH-MC | 19.23 (16.57–22.32) | 5.97 (5.23–6.83) | 40.03 (34.01–47.12) | 3.22 | 2.08 | |
| Dihydro-(R,S)-4-MC | 13.51 (11.72–15.58) | 32.35 (28.13–37.20) | 66.86 (53.64–83.35) | 0.42 | 4.94 | + |
| Dihydro-(S,R)-4-MC | 15.46 (13.71–17.43) | 41.80 (36.54–47.81) | 178.3 (157.8–201.3) | 0.37 | 11.53 | |
| Dihydro-(R,R)-4-MC | 8.05 (6.39–10.23) | 18.10 (16.29–20.11) | 74.58 (62.52–88.82) | 0.44 | 9.26 | + |
| Dihydro-(S,S)-4-MC | 22.63 (18.45–27.75) | 9.51 (8.44–10.71) | 32.24 (25.98–38.53) | 2.37 | 1.42 | |
| Dihydro-(R,S)-4-OH-MC | 99.14 (89.24–110.1) | 61.98 (55.87–68.75) | 383.4 (315.2–466.5) | 1.60 | 3.86 | − |
| Dihydro-(S,R)-4-OH-MC | 91.23 (83.66–99.46) | 83.39 (74.93–92.80) | 1,157 (875.7–1,530) | 1.09 | 12.68 | |
| Dihydro-(R,R)-4-OH-MC | 28.29 (22.94–34.90) | 46.50 (40.34–53.60) | 1,370 (1,047–1794) | 0.61 | 48.42 | − |
| Dihydro-(S,S)-4-OH-MC | 59.23 (52.27–67.12) | 12.56 (11.57–13.64) | 588 (499.9–691.7) | 4.71 | 9.92 | |
| Dihydro-(R,S)-4-OH-MMC | 84.49 (70.42–101.4) | 53.92 (46.07–63.11) | 496.2 (422–582.1) | 1.57 | 5.87 | − |
| Dihydro-(S,R)-4-OH-MMC | 77.03 (62.55–94.87) | 49.85 (46.07–63.11) | 3,158 (2,540–3,928) | 1.55 | 40.99 | |
| Dihydro-(R,R)-4-OH-MMC | 25.62 (22.15–29.64) | 36.95 (33.36–40.93) | 1735 (1,423–2,144) | 0.69 | 67.72 | − |
| Dihydro-(S,S)-4-OH-MMC | 160.8 (140.4–184.2) | 290.6 (259.8–325.1) | 1848 (1,518–2,250) | 0.55 | 11.49 | |
| (rac)-4-COOH-MC | 1,466 (1,133–1897) | 3,059 (2,177–4,298) | 11,432 (6,590–19,833) | 0.48 | 7.80 | + |