Meperidine Analogs In Vitro Data for Meperidine Analogs with Tritiated Radiotracers Tag DAT SERT Opioid Ki M and Dopamine IC50 M Uptake Ratio E Ar 3H WIN 35 428 3H Paroxetine 3H DAMGO 3H Dopamine DAT SERT DAT 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 CN 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 CO2Et 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 100 M 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