Binding of the cocaine analog 2 beta-[3H] 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. [3H]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 mM Na2SO4 and pH 9.5, the KD for [3H]CFT is 232 +/- 71 nM. The number of specific [3H]CFT binding sites on the membrane vesicles is equal to the number of serotonin transporters, as measured by [3H]imipramine binding. Binding of imipramine and CFT appeared to be mutually competitive. These results suggest that [3H]CFT and cocaine bind to the serotonin transporter at a site close to but distinct from the antidepressant binding site.
Rudnick
G
G
Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06510.
Wall
S C
SC
D001692:Biological Transport / Q000187:drug effects; D001798:Blood Proteins / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002712:Chlorides / Q000494:pharmacology; D003042:Cocaine / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007099:Imipramine / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins; D012964:Sodium / Q000494:pharmacology
D001798:Blood Proteins; D002352:Carrier Proteins; D002712:Chlorides; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; C021279:(1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester; D012964:Sodium; D003042:Cocaine; D007099:Imipramine; D011188:Potassium