Metaphit inhibits dopamine transport and binding of [3H]methylphenidate, a proposed marker for the dopamine transport complex

Metaphit, an acylating derivative of phencyclidine, was shown to interact with components of the dopamine nerve terminal in rat striatal tissue. This compound, previously demonstrated to be an irreversible inhibitor at the phencyclidine receptor, was shown in these experiments to irreversibly inhibit synaptosomal [3H]dopamine uptake. It also inhibited binding of [3H]methylphenidate to its recognition site, which is thought to be a subunit of the dopamine transporter. Although the inhibition was due primarily to a reduction in the binding and transport capacity of the systems studied, increases in the apparent KD of [3H]methylphenidate and the Km of [3H]dopamine were also observed. Differences in the behavior of Metaphit and phencyclidine in these dopaminergic systems compared to their effects on the NMDA receptor-linked phencyclidine receptor suggest that Metaphit may be interacting with two distinct molecular sites in the rat striatum.