Table 3.
In vitro studies demonstrating evidence of neurotoxicity by cathinone derivatives in various cell lines.
| Cell type | Drug | Neurotoxicity | Reference |
|---|---|---|---|
| SH-SY5Y (dopaminergic neuron) | mephedrone | ↑ LDH release (>500 μM) ↓ MT activity (≥1 mM) ↑ redox activity |
(den Hollander et al. 2014) |
| mephedrone | ↑ LDH release (≥1 mM) ↑ ROS production (≥1 mM) ↑ oxygen consumption rate (≥1 mM) ↑ p53 levels (≥1 mM) ↑ TNFα levels (≥1 mM) |
(den Hollander et al. 2015) | |
| pyrovalerone | ↓ cell viability (≥200 μM) ↓ MT function (≥200 μM) |
(Wojcieszak et al. 2016) | |
| MDPV | ↓ cell viability (≥100 μM) ↓ MT function (≥100 μM) |
(Wojcieszak et al. 2016) | |
| ↑ LDH release (≥1 mM) ↓ proliferation (≥250 μM) ↑ apoptosis (≥250 μM) ↑ ROS production (≥10 μM) |
(Rosas-Hernandez et al. 2016) | ||
| ↑ autophagy (>750 μM) ↑ ROS/RNS production (>1 mM) ↑ apoptosis (>1 mM) |
(Valente et al. 2017a) | ||
| ↑ cell death (EC50=1.5 mM) ↑ LDH release (EC50=1.5 mM) ↑ ROS/RNS production (>1.2 mM) ↑ apoptosis (>1.2 mM) ↑ oxidized glutathione (>1.2 mM) ↓ reduced glutathione (>1.2 mM) |
(Valente et al. 2017b) | ||
| methylone | ↑ LDH release (>1 mM) | (den Hollander et al. 2014; den Hollander et al. 2015) | |
| ↑ autophagy (>1 mM) ↑ ROS/RNS production (>1 mM) ↑ apoptosis (>1 mM) |
(Valente et al. 2017a) | ||
| ↑ cell death (EC50=2.5 mM) ↑ LDH release (EC50=3.2 mM) ↑ ROS/RNS production (>1.9 mM) ↑ apoptosis (>1.9 mM) |
(Valente et al. 2017b) | ||
| α-PVT | ↓ cell viability (≥25 μM) ↓ MT function (≥25 μM) |
(Wojcieszak et al. 2016) | |
| α-PV9 | ↓ cell viability (≥200 μM) | (Wojcieszak et al. 2016) | |
| ↓ MT function (≥200 μM) ↑ LDH release (≥200 μM) |
|||
| cultured cortical neurons | mephedrone | ↓ cell viability (>100 μM) | (Martinez-Clemente et al. 2014) |
| methylone | ↓ cell viability (>300 μM) | (Lopez-Arnau et al. 2014a) | |
| HT22 (neuronal) | 3-fluoro- methcathinone |
↓ cell viability (≥1 mM) ↓ cell cycle arrest (≥1 mM) ↑ ROS production (≥1 mM) ↑ autophagy (≥1 mM) ↑ apoptosis (≥1 mM) |
(Siedlecka-Kroplewska et al. 2014) (Siedlecka-Kroplewska et al. 2018) |
| SK-N-SH (neuronal) | α-PNP | ↓ cell viability (≥10 μM) ↑ ROS production (50 μM) ↑ lipid peroxidation (≥50 μM) ↑ apoptosis (≥10 μM) ↑ autophagy (≥10 μM) |
(Matsunaga et al. 2017) |
| TGW (neuronal) | α-PNP | ↓ cell viability (≥20 μM) | (Matsunaga et al. 2017) |
| pulmonary | α-PNP | ↓ cell viability (≥10 μM) | (Matsunaga et al. 2017) |
| kidney | α-PNP | ↓ cell viability (≥20 μM) | (Matsunaga et al. 2017) |
| PC12 | Cathinone phthalimide | ↑ LDH release (≥10 μM) ↓ MT function (≥1 mM) |
(Lantz et al. 2017) |
| aortic smooth muscle | α-PNP | ↓ cell viability (≥20 μM) | (Matsunaga et al. 2017) |
| endothelial cells | pyrovalerone | ↓ cell viability (>30 μM) ↓ MT function (>100 μM) |
(Wojcieszak et al. 2016) |
| MDPV | ↓ cell viability (>30 μM) ↓ MT function (>100 μM) ↑ LDH release (>100 μM) ↑ LDH release (≥500 μM) ↓ proliferation (≥1 mM) ↑ ROS production (≥500 μM) |
(Wojcieszak et al. 2016) (Rosas-Hernandez et al. 2016) | |
| α-PVT | ↓ cell viability (≥25 μM) ↓ MT function (≥25 μM) |
(Wojcieszak et al. 2016) | |
| α-PV9 | ↓ cell viability (≥100 μM) ↓ MT function (≥100 μM) ↑ LDH release (≥100 μM) |
(Wojcieszak et al. 2016) | |
| α-PNP | ↓ cell viability (≥5 μM) | (Matsunaga et al. 2017) | |
| intestinal cells | α-PNP | ↓ cell viability (≥20 μM) | (Matsunaga et al. 2017) |
| hepatocytes | mephedrone | ↑ cell death (≥2 mM) ↑ ROS production (≥1 mM) ↓ MT function (≥1 mM) |
(Luethi et al. 2017) |
| ↓ cell viability (EC50=1.3 mM) | (Gaspar et al. 2018) | ||
| pyrovalerone | ↓ cell viability (≥300 μM) ↓ MT function (≥300 μM) |
(Wojcieszak et al. 2016) | |
| MDPV | ↓ cell viability (>100 μM) ↓ MT function (>100 μM) ↑ LDH release (>100 μM) |
(Wojcieszak et al. 2016) | |
| ↑ cell death (EC50=0.7 mM) | (Araujo et al. 2015) | ||
| ↑ cell death (≥2 mM) ↑ ROS production (≥2 mM) ↓ MT function (≥1 mM) |
(Luethi et al. 2017) | ||
| ↓ cell viability (≥200 μM) ↑ LDH release (≥200 μM) ↑ ROS/RNS production (≥1.6 mM)* ↑ apoptosis (≥1.6 mM)* |
(Valente et al. 2016) | ||
| ↓ cell viability (≥200 μM) ↑ LDH release (≥400 μM) |
(Silva et al. 2016) | ||
| methcathinone | ↓ cell viability (EC50=5.8 mM) | (Gaspar et al. 2018) | |
| methylone | ↑ cell death (EC50=1.2 mM) | (Araujo et al. 2015) | |
| ↑ cell death (≥2 mM) | (Luethi et al. 2017) | ||
| methedrone | ↑ cell death (≥2 mM) | (Luethi et al. 2017) | |
| naphyrone | ↑ cell death (≥0.5 mM) ↑ ROS production (≥200 μM) ↓ MT function (≥200 μM) |
(Luethi et al. 2017) | |
| pentedrone | ↑ cell death (EC50 = 0.7 mM) | (Araujo et al. 2015) | |
| buphedrone | ↓ cell viability (EC50=2.9 mM) | (Gaspar et al. 2018) | |
| 4-MEC | ↑ cell death (EC50=1.3 mM) | (Araujo et al. 2015) | |
| ↓ cell viability (EC50=1.5 mM) | (Gaspar et al. 2018) | ||
| 4-MDMC | ↓ cell viability (EC50=0.8 mM) | (Gaspar et al. 2018) | |
| 4-MDEC | ↓ cell viability (EC50=5.4 mM) | (Gaspar et al. 2018) | |
| 3,4-DMMC | ↓ cell viability (EC50=1.2 mM) | (Gaspar et al. 2018) | |
| DEC | ↓ cell viability (EC50=6.6 mM) | (Gaspar et al. 2018) | |
| DEB | ↓ cell viability (EC50=1.8 mM) | (Gaspar et al. 2018) | |
| DEP | ↓ cell viability (EC50=1.5 mM) | (Gaspar et al. 2018) | |
| DMC | ↓ cell viability (EC50=7.8 mM) | (Gaspar et al. 2018) | |
| DMB | ↓ cell viability (EC50=1.2 mM) | (Gaspar et al. 2018) | |
| DMP | ↓ cell viability (EC50=1.1 mM) | (Gaspar et al. 2018) | |
| NEC | ↓ cell viability (EC50=2 mM) | (Gaspar et al. 2018) | |
| NEB | ↓ cell viability (EC50=1.2 mM) | (Gaspar et al. 2018) | |
| NEP | ↓ cell viability (EC50=1.5 mM) | (Gaspar et al. 2018) | |
| MPPP | ↓ cell viability (EC50=2.3 mM) | (Gaspar et al. 2018) | |
| α-PBP | ↓ cell viability (EC50=4.9 mM) | (Gaspar et al. 2018) | |
| α-PPP | ↓ cell viability (EC50=6.2 mM) | (Gaspar et al. 2018) | |
| α-PVP | ↓ cell viability (EC50=2 mM) | (Gaspar et al. 2018) | |
| α-PNP | ↓ cell viability (≥20 μM) | (Matsunaga et al. 2017) | |
| α-PVT | ↓ cell viability (≥1 μM) ↓ MT function (>1 μM) |
(Wojcieszak et al. 2016) | |
| α-PV9 | ↓ cell viability (>25 μM) ↓ MT function (>25 μM) ↑ LDH release (≥200 μM) |
(Wojcieszak et al. 2016) |
Concentration at which statistically significant effects were observed as compared to untreated cells are provided in parentheses.
*
denotes concentrations where effects observed under normothermic conditions that were also observed at lower concentration under hyperthermic conditions. Abbreviations: α-PNP, α-pyrrolidinononanophenone; α-PVT; α-pyrrolidinovalerothiophenone; α-PV9, α-pyrrolidinooctanophenone; α-PBP, α-pyrrolidinobutiophenone; α-PPP, α-pyrrolidinopropiophenone; 3,4-dimethylmethcathinone (3,4-DMMC); 4-MDEC, 4-methyldiethylcathinone; 4-MDMC, 4-methyldimethcathinone; 4-MEC, 4-ethylethcathinone; DEB, diethylbuphedrone; DEP, diethylpentedrone; DMB, dimethylbuphedrone; DMC, dimethylcathinone; DMP, dimethylpentedrone, EC50, effective concentration 50; LDH, lactose dehydrogenase; MPPP, 4-methyl-α-pyrrolidinopropiophenone; MT, mitochondria; ND, not determined; NEB, N-ethylbuphedrone; NEC, N-ethylcathinone; NEP, N-ethylpentedrone; RNS, reactive nitrogen species; ROS, reactive oxygen species.