VAS-972

In our effort to develop a novel radioligand selective for the dopamine transporter, compound 1b (O-972) was designed and characterized. The compound 1b was characterized for its binding both in monkey and rat striatum tissue, which demonstrated its high selectivity for the dopamine transporter (DAT) when its binding was compared with that at the serotonin transporter (SERT). The compound 5, which is a precursor for the tritiated radiolabel ligand [3H]O-972, was synthesized and biologically characterized. The preliminary characterization of this novel radioligand revealed its strong binding affinity for the DAT. Thus, the pharmacological profile of [3H]O-972 indicated that DAT inhibitors, which include GBR 12909, mazindol, CFT, and cocaine, could potently displace this novel radioligand from monkey brain striatum tissue. On the other hand, compounds known to be not selective for and potent at the DAT were very weak to do so. Initial binding results also indicate that [3H]O-972 may interact with the DAT in a manner that is not identical to that for GBR 12909 and tropane analogs.