COMPARISON OF INHIBITION OF 5-HYDROXYTRYPTAMINE UPTAKE BY METHADONE AND ITS CONGENERS IN HUMAN PLATELETS

Whether methadone caused an appreciable inhibition of uptake of 5-HT [5-hydroxytryptamine] by human platelets at concentrations likely to be encountered in a methadone-maintenance situation was studied in vitro. The effects of several other methadone congeners were also studied in an attempt to identify a structural requirement for uptake inhibition. Imipramine and chlorimipramine were tested for comparison, as these were potent inhibitors of 5-HT uptake. The extent of in-vitro inhibition may be greater than that occurring in vivo, due to the fact that .apprx. 85% of the methadone in plasma is protein bound. Since incubations contained only 25% plasma, a greater proportion of methadone in the incubations may be expected to be unbound, when compared to whole plasma. Imipramine was about 4 times as potent as methadone. The inhibition of platelet 5-HT uptake by methadone and its congeners showed structural specificity in that compounds with the 6R configuration were more potent than compounds with the 6S configuration. Methadone was a more potent inhibitor of 5-HT uptake by platelets than previously recognized, which raised the possibility that methadone maintenance may cause depletion of platelet 5-HT in vivo.