Article Figures & Data
Figures
- Fig. 1.
Chemical structures of 4-chloromethcathinone (4-CMC), 4-chloroethcathinone (4-CEC), and 4-chloro-α-pyrrolidinopropiophenone (4-CαPPP) compared with 4-methylmethcathinone (mephedrone).
- Fig. 2.
Effects of synthetic cathinones on inhibition of uptake (upper panels) and stimulation of release (lower panels) at dopamine (DAT), norepinephrine (NET), and serotonin (SERT) transporters in rat brain synaptosomes. For uptake assays, synaptosomes were incubated with different concentrations of test drugs in the presence of 5 nM [3H]dopamine, 10 nM [3H]norepinephrine, or 5 nM [3H]serotonin. Data are expressed as a percentage of transmitter uptake (± S.D.) for three experiments. For release assays, synaptosomes were preloaded with 9 nM [3H]MPP+ (DAT and NET) or 5 nM [3H]5-HT (SERT) and then incubated with different concentrations of test drugs to evoke release via reverse transport. Data are expressed as a percentage of [3H]substrate release (± S.D.) for three experiments.
- Fig. 3.
Time course for the effects of various doses of 4-CMC on BP, HR, activity, and temperature over 3 hours in rats implanted with telemetry transmitters. Values represent a 10-minute mean for BP, HR, and temperature or the sum of counts over 10 minutes for activity for each rat. Solid symbols indicate significant difference from saline. Each point is the mean ± S.E.M. of seven rats.
- Fig. 4.
Dose-effect functions for mephedrone (n = 5), 4-CMC (n = 7), 4-CEC (n = 5), and 4-CαPPP (n = 5) on BP, HR, activity, and temperature in rats implanted with telemetry transmitters. Data points are the mean ± S.E.M. over the first hour of the session. Points over S are for the saline test conducted in conjunction with each drug. Solid symbols indicate significant differences from the respective saline.
- Fig. 5.
Effects of 10 mg/kg 4-CMC alone or in combination with the alpha-adrenergic antagonist prazosin (Praz, 0.3 mg/kg, n = 5), the dopamine D1 antagonist SCH23390 [SCH, 0.1 mg/kg, n = 5 (except for SCH + 4CMC, n = 4)] and the ganglionic blocker chlorisondamine (chloro 1.0 mg/kg, n = 5) on BP, HR, and activity. Each bar is the mean ± S.E.M. for the first hour of the session. #Represents significant difference from vehicle (Sal or Water) + saline (Sal). *Represents significant difference from vehicle + 10 mg/kg 4-CMC.
Tables
- TABLE 1
Effects of synthetic cathinones analogs on inhibition of [3H]neurotransmitter uptake and release of [3H]MPP+ via DAT and NET or [3H]5-HT via SERT in rat brain synaptosomes
Data are mean ± S.D. for n = 3 experiments performed in triplicate.
Drug Uptake Inhibition at DAT
IC50 (nM)Uptake Inhibition at NET
IC50 (nM)Uptake Inhibition at SERT
IC50 (nM)Mephedrone 769 ± 106 319 ± 40 600 ± 99 4-CMC 1014 ± 78 559 ± 57 542 ± 38 4-CEC 1455 ± 110 2848 ± 292 589 ± 44 4-CαPPP 569 ± 57 764 ± 79 >10,000 Release at DAT Release at NET Release at SERT EC50 (nM) [% Emax]a EC50 (nM) [% Emax]a EC50 (nM) [% Emax]a Mephedrone 103 ± 16 [114] 83 ± 20 [100] 188 ± 22 [108] 4-CMC 91 ± 11 [109] 99 ± 18 [102] 169 ± 20 [109] 4-CEC Inactive 3058 ± 547 [81] 191 ± 26 [107] 4-CαPPP Inactive Inactive Inactive a% Emax is defined as percentage of maximal releasing response as described in Materials and Methods.
