Baclofen for alcohol-dependence: anticraving or partial substitution?

To the Editors: A lthough the report by Ayan-Oshodi et al claims that LY404,039 does not have appreciable affinity for the dopamine D2 receptor, this claim is not correct. The only report where LY404,039 has been tested on the cloned D2 receptor clearly showed that LY404,039 inhibited the binding of 2 nM [H]domperidone to the human cloned D2 receptor with a dissociation constant of 8.2 nM at the high-affinity site of the D2 receptor and a dissociation constant of 1640 nM at the low-affinity site, as shown in Figure 1. Furthermore, the in vitro action of LY404,039 (Fig. 1, bottom) suggests a partial agonist action at D2 receptors. Nevertheless, these preclinical actions do not appear to be sufficient for LY404,039 to exert a convincing clinical antipsychotic action.