Synthesis and ligand binding of cocaine isomers at the cocaine receptor.
The cocaine binding site at the dopamine transporter has been found to be stereoselective. Thus, the seven possible stereoisomers of (-)-cocaine have been synthesized and found to inhibit [3H]-2 beta-carbomethoxy-3 beta-(4-fluoro-phenyl)tropane [( 3H]WIN 35,428) with potencies ranging from 1/60 to 1/600 of that of (-)-cocaine. The synthesis and characterization of all new compounds is presented.
Carroll
F I
FI
Chemistry and Life Sciences, Research Triangle Institute, North Carolina 27709.
Lewin
A H
AH
Abraham
P
P
Parham
K
K
Boja
J W
JW
Kuhar
M J
MJ
D000818:Animals; D001667:Binding, Competitive; D002352:Carrier Proteins; D002462:Cell Membrane / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D003042:Cocaine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D008297:Male; D015394:Molecular Structure; D051381:Rats; D011919:Rats, Inbred Strains; D011955:Receptors, Drug / Q000378:metabolism*; D013237:Stereoisomerism
D002352:Carrier Proteins; D011955:Receptors, Drug; C061445:cocaine receptor; C021279:(1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester; D003042:Cocaine