anyone know anything about the meperidine analogs that are mu agonists but also inhibit the reuptake of dopamine, serotonin, and norepinephrine; in addition to inhibiting reputake it also causes dopamine and norepinephrine release. some of the analogs were a hybrid of the meperidine and nocaine structures. the nocaine class of drugs are piperidine-derived cocaine analogs. sounds very interesting like lefetamine and I think fencamfamine and tapentadol, drugs that have both opioid and stimulant properties. meperidine itself does inhibit some dopamine and norepinephrine reuptake but I'm not sure how "speedy" it is, I've heard demerol is more speedy than sedating. who knows maybe one of these analogs may even have some MDMA-like qualities since it also effects serotonin.
Synthesis and biological evaluation of meperidine analogues at monoamine transporters.
Lomenzo SA, Rhoden JB, Izenwasser S, Wade D, Kopajtic T, Katz JL, Trudell ML.
Department of Chemistry, University of New Orleans, New Orleans, LA 70148, USA.
A series of aryl-substituted meperidine analogues was synthesized, and the binding affinities were determined at the DAT, SERT, and NET as well as at mu-opioid receptors. Generally the analogues exhibited increased affinity for the DAT and SERT relative to meperidine but exhibited low binding affinity for the NET. The 2-naphthyl derivative 7f was the most potent ligand at the SERT (K(i) = 0.0072 muM) and was the most selective ligand for the SERT over the DAT (DAT/SERT = 158) and mu-opioid receptors (mu/SERT = 281). The 3,4-dichlorophenyl derivative 7e was the most potent ligand at the DAT (K(i) = 0.125 muM) and was the most selective ligand for the DAT over mu-opioid receptors (mu/DAT = 16.3) but remained slightly more selective for the SERT over the DAT(DAT/SERT = 6.68). Three compounds, the 3,4-dichlorophenyl derivative 7e and the 2-naphthyl analogues 6f and 7f, were identified that were more potent at the DAT than meperidine and that exhibited well-defined biphasic dopamine uptake inhibition similar to meperidine. However, none of the analogues tested produced locomotor effects or substituted for cocaine in drug discrimination studies, suggesting that the mu-opioid effects of these analogues may contribute to the poor efficacy observed in vivo.