Both residues differ in NET and DAT. We find in the corresponding positions V148 and F72 in NET and V152 and F76 in DAT. These ROCK inhibitor docking results are in line with our experimental observation of the different behavior in the binding of aminorex to SERT compared to NET and DAT. A large part of illicitly sold drugs

are marketed in adulterated form; these commercialized preparations often may contain several additional, also pharmacologically active compounds. There are two obvious explanations why certain substances are used to adulterate illicit drugs: substances are added because they are cheap, have similar chemical appearance and taste and therefore increase the profit. Alternatively, the additives enhance the psychoactive effects of the drug by exerting a pharmacological effect per se. Accordingly, they contribute to the drug-specific reinforcement, learn more gain more customers and thus increase profits. To our knowledge this work demonstrated for the first time that levamisole as Modulators cocaine adulterant itself directly inhibits the neurotransmitter transporters DAT, SERT and NET. Moreover, we found a cocaine-like effect of the levamisole metabolite aminorex at the DAT and

the NET and an amphetamine-like effect at SERT. Therefore, it can be assumed that levamisole is used to prolong the effect of cocaine: it is possible that after the cocaine effect “fades out” the aminorex effect “kicks in”. However, the physiological consequences of combined cocaine-aminorex administration are still unclear. To our knowledge there are no reports on how the combination of cocaine and aminorex influences drug experience or brain physiology. It can be assumed that massive elevation

of extracellular serotonin levels not only by inhibiting uptake (via cocaine) but also increasing efflux (via aminorex) can be the consequence. The ‘checkit!’ program offers a glimpse into the the epidemiology of the problem: Two-thirds of the cocaine samples that were analyzed within the past year were contaminated with moderate to exceedingly high concentrations of levamisole. The latter highlight the risk inherent in adulteration of street drugs, namely the occurrence of severe or life-threatening intoxications. Therefore it is important to mention that consumption of cocaine adulterated with levamisole not only provokes severe agranulocytosis (Buchanan and Lavonas, 2012) but also induces the risk of pulmonary hypertension due to aminorex (Fishman, 1999b). The work of HHS, GFE and MF was supported by the Austrian Science Fund/FWF (grant F35). The drug prevention project ‘checkit!’ is financially supported by the Department of Addiction and Drug Coordination (STW) of the City of Vienna. “
“During synaptic transmission, glutamate transporters restrict the spatiotemporal pattern of ionotropic and metabotropic glutamate receptor signaling (for review see Tzingounis and Wadiche, 2007).