"==Meperidine Analogs==
In Vitro Data for Meperidine Analogs with Tritiated Radiotracers.

Tag
DAT / SERT / Opioid (Ki, μM) and Dopamine (IC50, μM)
Uptake Ratio


E
Ar
[3H]WIN 35,428
[3H]Paroxetine
[3H]DAMGO
[3H]Dopamine
DAT/SERT
μ/DAT
μ/SERT

CO2EtPh17.8 ± 2.70.413 ± 0.0440.9212.6 ± 1.243.10.0522.13
CNp-F45†10.1 ± 0.415†8†ndndnd
CNp-Cl22.0 ± 10.15.11 ± 0.5936.8 (51)†36†4.311.670.18
CNp-I8.34 ± 0.670.430 ± 0.003417.3 (61)†36.7 ± 1.319.42.0740.2
CNp-Me41.8 ± 6.113.7 ± 0.440.6 (46)†22†3.050.972.96
CNm,p-Cl22.67 ± 0.240.805 ± 0.1240.0 (46)†11.1 ± 1.23.3215.049.7
CNβ-Naph2.36 ± 0.660.125 ± 0.02215.4 (61)†21.8 ± 1.218.96.53123
CO2Etp-F10.7 ± 2.30.308 ± 0.0261.4747†34.70.144.77
CO2Etp-Cl4.10 ± 1.270.277 ± 0.0404.4126.9 ± 1.214.81.0815.9
CO2Etp-I3.25 ± 0.200.0211 ± 0.00242.3511.1 ± 1.21550.72111
CO2Etp-Me12.4 ± 5.21.61 ± 0.112.6776.2 ± 1.27.690.221.66
CO2Etm,p-Cl20.125 ± 0.0150.0187 ± 0.00262.041.40 ± 1.256.6816.3109
CO2Etβ-Naph1.14 ± 0.380.0072 ± 0.00012.0311.6 ± 1.31581.78282
All values are the mean ± SEM of three experiments performed in triplicate. † Percent inhibition at highest dose tested (100μM).
Some analogs of meperidine were prepared, initially with a bias toward improving DAT binding, but it turned out that these analogs favor the SERT and can even be made selective for this transporter under optimum circumstances (Stacey Lomenzo, Sari Izenwasser).Bioorganic & Medicinal Chemistry Letters, Volume 9, Issue 23, 6 December 1999, Pages 3273-3276 Stacey A. Lomenzo, Sari Izenwasser, Robert M. Gerdes, Jonathan L. Katz, Theresa Kopajtic and Mark L. TrudellLomenzo, S. A.; Rhoden, J. B.; Izenwasser, S.; Wade, D.; Kopajtic, T.; Katz, J. L.; Trudell, M. L.
J. Med. Chem.; (Article); 2005; 48(5); 1336-1343. Even in light of this early warning sign, the authors were still content to press ahead and modify the carboethoxy ester of the p,m-Cl2 analog into a variety of spin-out molecules in a futile attempt to approve DAT binding. (Jill B. Rhoden)Bioorganic & Medicinal Chemistry Volume 13, Issue 19, 1 October 2005, Pages 5623-5634 Although this effort was unprofitable and even detrimental, some of the new compounds were even more SERT selective and robust. None of the analogs tested produced LMA effects or substituted for cocaine in drug discrimination studies. The authors hypothesized that opi