Legends of figure
Figure 1. Chemical structure of the aminovalerophenone derivatives. Compounds share a similar chemical structure, only differing by their amino-substituent: methylamino- (pentedrone), ethylamino- (N-ethyl-pentedrone), diethylamino- (N,N-diethyl-pentedrone), pyrrolidine ring (α-PVP) or piperidine ring (α-PpVP).
Figure 2. Effects of aminovalerophenone derivatives on cumulative locomotor activity in CD-1 mice. Bars represent mean ± SEM of the distance travelled in 60 min. Panel A: saline and pentedrone 30 mg kg-1 groups, N=9/group; pentedrone 3 mg kg-1 and 10 mg kg-1 groups, N=10/group. Panel B: saline, N-ethyl-penedrone 1, 3, and 10 mg kg-1, N=10/group. Panel C: saline, N,N-diethyl-pentedrone 3.5, 12.5, 35 mg kg-1, N=10/group. Panel D: saline, α-PVP 1, 3, 10 mg kg-1, N=11/group. Panel E: saline, α-PpVP 7.5, 25, 75 mg kg-1, N=10/group. *P<0.05 vs saline; #P<0.05, vs the lower drug-dose; $P<0.05 vs the medium drug-dose.
Figure 3. Effects of aminovalerophenone derivatives on conditioned place preference (CPP) test in CD-1 mice. Bars represent mean ± SEM of the preference score (difference between the time spent in the drug-paired compartment on the test day and the pre-conditioning day). Panel A: saline and pentedrone 3 and 10 mg kg-1, N=14/group, pentedrone 30 mg kg-1, N=13/group. Panel B: saline and N-ethyl-penedrone 1 mg kg-1, N=14/group, N-ethyl-penedrone 3 mg kg-1, N=13/group, N-ethyl-penedrone 10 mg kg-1 N=12/group. Panel C: saline, N,N-diethyl-pentedrone 35 mg kg-1, N=14/group, N,N-diethyl-pentedrone 3.5 mg kg-1, N=12/group, N,N-diethyl-pentedrone 12.5 mg kg-1, N=13/group. Panel D: saline, α-PVP 1, 3, 10 mg kg-1, N=14/group. Panel E: saline, α-PpVP 7.5, 25, 75 mg kg-1, N=14/group. *P<0.05 vs saline; #P<0.05 vs the lower drug-dose.
Figure 4. Molecular representation of hDAT binding site identifying the three different subsites A to C by colored surfaces (A). Binding mechanism predicted by molecular docking for α-PVP (B), N-ethyl-pentedrone (C), pentedrone (D), N,N-diethyl-pentedrone (E) and α-PpVP (F).