Article Figures & Data
Figures
- Fig. 1.
Chemical structures of AEPEA, MEPEA, and DEPEA as compared with amphetamine and methamphetamine.
- Fig. 2.
Effects of amphetamine and PEA analogs on inhibition of uptake and stimulation of efflux (i.e., release) at DAT (upper panels) or NET (lower panels) in rat brain synaptosomes. For uptake assays, synaptosomes were incubated with different concentrations of test drugs in the presence of 5 nM [3H]dopamine ([3H]DA) or [3H]norepinephrine ([3H]NE). Data are means ± S.D., expressed as a percentage of transmitter uptake for N = 3 experiments performed in triplicate. For release assays, synaptosomes were preloaded with 9 nM [3H]MPP+ and then incubated with different concentrations of test drugs to evoke release via reverse transport. Data are means ± S.D., expressed as a percentage of [3H]MPP+ release for three experiments performed in triplicate.
- Fig. 3.
Effects of GBR12909 (GBR) or desipramine (DMI) on drug-induced release of [3H]MPP+ at DAT (upper panels) or NET (lower panels). For substrate reversal assays, synaptosomes were preloaded with 9 nM [3H]MPP+, and then test drugs were incubated with or without GBR12909 (1 nM) for DAT assays or desipramine (8 nM) for the NET assays. Data are means ± S.D. expressed as a percentage of [3H]MPP+ release for three experiments performed in triplicate.
- Fig. 4.
Time course effects of AEPEA administration on BP, HR, motor activity, and core body temperature. Male rats bearing biotelemetry transponders received subcutaneous injection of 1, 3, or 10 mg/kg AEPEA or its saline vehicle and were returned to their home cages. Five minutes later, cages were placed atop telemetric receivers. Data were collected in 10-minute epochs for 3 hours. Data are expressed as means ± S.E.M. for five rats per group.
- Fig. 5.
Dose-effect functions for amphetamine (Amph) and PEA analogs on BP, HR, motor activity, and core body temperature. Data represent mean values across the full 3-hour session. Solid symbols indicate significant differences from the respective saline group. Data are means ± S.E.M. for five rats per group.
Tables
- TABLE 1
Effects of amphetamine and PEA analogs on the uptake of [3H]neurotransmitters and on the release of [3H]MPP+ at DAT or NET in rat brain synaptosomes
Data are means ± S.D. for N = 3 experiments performed in triplicate. %Emax is defined as the percentage of maximal releasing response induced by 10 µM tyramine. DAT/NET ratio = (DAT IC50−1)/(NET IC50−1); higher value indicates greater DAT selectivity.
Drug Uptake Inhibition at DAT [IC50 (nM)] Uptake Inhibition at NET [IC50 (nM)] DAT/NET Ratio Amphetamine 122 ± 12 69 ± 9 0.56 AEPEA 3366 ± 333 573 ± 78 0.16 MEPEA 2248 ± 245 503 ± 95 0.22 DEPEA 510 ± 38 427 ± 60 0.84 Release at DAT EC50 (nM) (%Emax) Release at NET EC50 (nM) (%Emax) Amphetamine 5 ± 1 (102) 8 ± 1 (96) 1.6 AEPEA 273 ± 36 (101) 80 ± 17 (100) 0.29 MEPEA 179 ± 25 (101) 58 ± 12 (96) 0.32 DEPEA 604 ± 159 (43) 209 ± 35 (82) 0.35 - TABLE 2
G Protein–coupled receptorome screening for amphetamine and PEA analogsa
Data represent Ki (nanomolar) values obtained from nonlinear regression using the Cheng-Prusoff equation when inhibition was >50%. The results for amphetamine (AMPH) were reported previously (Schindler et al., 2019).
AMPH AEPEA MEPEA DEPEA Serotonin 5-HT1A 2625 >10,000 1966 1588 5-HT2B 971 >10,000 >10,000 >10,000 Norepinephrine α2A 420 >10,000 >10,000 >10,000 α2B 192 1362 411 1013 α2C 171 1404 1805 2320 NET 31 >10,000 >10,000 108 Dopamine DAT >10,000 >10,000 >10,000 124 Sigma σ2 >10,000 >10,000 806 1352 Histamine H1 >10,000 2541 5800 >10,000 ↵a Ki values for the following receptors were >10,000 nM for all four drugs tested: serotonin receptors 5-HT1B, 5-HT1D, 5-HT1E, 5-HT2A, 5-HT2C, 5-HT3, 5-HT5A, 5-HT6, 5-HT7, and SERT; norepinephrine receptors α1A, α1B, α1D, β1, β2, and β3; dopamine D1, D2, D3, D4, and D5; histamine receptors H2, H3, and H4; opioid receptors μ, κ, and δ; muscarinic receptors M1, M2, M3, M4, and M5; σ1 receptor; benzodiazepine and peripheral benzodiazepine receptors.
In this issue
Amphetaminelike Effects of α-Ethylphenethylamine Analogs
