BINDING OF THE COCAINE ANALOG 2-BETA-[H-3] CARBOXYMETHOXY-3-BETA-(4-FLUOROPHENYL)TROPANE TO THE SEROTONIN TRANSPORTER

The cocaine analog 2-beta-carboxymethoxy-3-beta-(4-fluorophenyl)tropane (CFT) binds to platelet plasma membrane vesicles. [H-3] CFT binding is blocked equally well by cocaine and imipramine. Specific (cocaine-sensitive) binding requires Na+ and is inhibited by H+ and Cl- ions. At 150 nM Na2SO4 and pH 9.5, the K(D) for [H-3]CFT is 232 +/- 71 nM. The number of specific [H-3]CFT binding sites on the membrane vesicles is equal to the number of serotonin transporters, as measured by [H-3]imipramine binding. Binding of imipramine and CFT appeared to be mutually competitive. These results suggest that [H-3]CFT and cocaine bind to the serotonin transporter at a site close to but distinct from the antidepressant binding site.